Referenced Quotes about HIV/AIDS Tests and Measurements

Alberta Reappraising AIDS Society

David Crowe, President
Phone: +1-403-289-6609
Fax: +1-403-206-7717

Roger Swan, Treasurer
Box 61037, Kensington Postal Outlet
Calgary, Alberta T2N 4S6
Phone: +1-403-220-0129

Referenced Quotes about HIV/AIDS Tests and Measurements

False Positives

Although it is often denied, there is a lot of evidence that HIV tests can generate false positives. In fact, with no proper validation of HIV tests, it is not clear whether or not all positive HIV tests are false positives.

Johnson C. Factors that cause false-positive HIV antibody test results. OMSJ. 2011 Sep 18
“Liam Scheff interviews a woman, a clinical psychologist, has an HIV test before entering a new relationship. She tests positive on both ELISA and Western Blot, but then a little later negative. [Audio 38:38]
“A [Washington] D.C. man says he walked around for five years thinking he was HIV-positive when he was actually not. Terry Hedgepeth says he was misdiagnosed in 2000 by the Whitman-Walker Clinic. He says the misdiagnosis drove him into a deep depression. In 2005, a friend suggested he seek holistic healing. He went to the Abundant Life Center where he was tested and told he was HIV-negative. A third round of testing at Johns Hopkins confirmed it. Hedgepeth launched a lawsuit, but it was thrown out because the law said you could only sue if there was physical injury. Then just last week, a D.C. Appeals Court expanded the law to include emotional injury and gave Hedgepeth the green light to sue.”
Clinic Wrongly Told Him He Was HIV-Positive. Fox News. 2011 Jul 7
“When Mr. S. was doing time at Rikers Island in the early 1990s…He received the unwelcome news that he was H.I.V. positive, though his T-cell count was still in the normal range.…He took his medications and showed up for his appointments, but he almost never got lab tests, since decades of drug use had obliterated his veins. Despite the other medical assaults on his body — diabetes, hypertension, hepatitis C, stubborn leg ulcers — his immune system remained intact…His T-cell count stayed high enough to protect him from opportunistic infections. He seemed to be one of the rare, lucky “nonprogressors.” But after several years of consistently robust T-cell counts, one of the nurse practitioners had a hunch. She asked the methadone doctor not just for a T-cell count but also for a new H.I.V. test. Lo and behold, it came back negative…over the years, thanks to his assiduous care, the [IV drug-induced] ulcers gradually healed until there were only thin snaking scars on his calves to mark their sites…after two decades of taking methadone at an impressively high dose, he abruptly tapered himself off. “I’ve had enough,” he told me bluntly.”
Ofri D. Stereotyping patients, and their ailments. NY Times. 2011 Jun 20
“In 2008 a blood test was offered to 190,141 pregnant women [in the Netherlands]…HIV prevalence was estimated to be between 0.04 and 0.08% in 2008 and was stable during the study period…False-positive HIV results occurred regularly; only 24-27% of women with a positive ELISA result also had a positive confirmation…After the introduction of screening in 2004, four children were born with HIV. Two mothers became pregnant before screening was introduced. One mother was HIV negative and probably became infected with HIV after the 12th week of pregnancy [but no evidence is offered that she actually had become HIV-positive]
Op de Coul EL et al. Antenatal screening for HIV, hepatitis B and syphilis in the Netherlands is effective. BMC Infect Dis. 2011;11:185.
“A father of five, who ran away after a private hospital here misdiagnosed him as HIV positive, has been awarded RM150,000 in general damages by a High Court for medical negligence and defamation…Outside the courtroom, a happy and relieved Nageswara said he would be reuniting with his wife and children whom he had not seen for nearly 10 years.”
Dielenberg P. Patient wrongly diagnosed with HIV awarded RM150,000. The Star (Malaysia). 2011 Mar 2
[Flavia recounts the experience of her friend who tested six times positive over several years but was very healthy. Later she went to another testing site and tested negative twice. Another woman describes her experience testing positive five times and then later negative.]
Davis R. Flavia recounting a friend’s conflicting “HIV Test” results. YouTube. 2011 Feb
[In response to a request for “an approved HIV virus test that detects the presence or absence 100% in the human body”] No medical test I know of is 100% accurate. In any case, there is some potential for a false-positive or false-negative result. No test stands alone as a basis for medical decisions. Test results are employed along with other information, such as medical history, physical examination, etc. Sorry I couldn’t be more helpful. (signed) David Banks, FDA Office of Special Health Issues”
Banks D. Email to Liam Scheff. Personal Correspondence. 2011 Feb 2
“A total of 1,051,701 donations during September 2006 through June 2009 were tested by Cobas Ampliscreen NAT [Nucleic Acid Test, i.e. ‘Viral Load’]. We performed an investigation of those blood donor samples that were NAT reactive but had negative screening test results for the corresponding virus-specific antibodies (anti-HCV and anti- HIV-1/2). For confirmatory testing, we performed a repeat AmpliScreen NAT in duplicate for the same virus using another tube of blood sample from the index donation. If one or both replicates were reactive, the specimen was classified as confirmed positive. If both replicates were non-reactive, the specimen was classified as not confirmed…for the five HIV NAT–unconfirmed samples, a suspected contamination event occurred once. In all other unconfirmed samples [two],we could not identify any reasons for the false positivity.”
Kakaiya R et al. False-positive nucleic acid test results for human immunodeficiency virus RNA and hepatitis C virus RNA: an underappreciated problem. Transfusion. 2011 Jan;51(1):225-6.
“We retrospectively analyzed the performance of the Architect HIV antigen/antibody (Ag/Ab) combination assay in a tertiary health care center with a situation of low HIV prevalence. The specificity and positive predictive value (PPV) were 99.78% and 31.21%, respectively. However, the specificity and PPV could increase to 99.99% and 89.70% using an arbitrary cutoff value. [This means that normally almost 70% of positive HIV tests are false positive but this could be improved to just over 1 out of 10 being false-positive, according to these researchers]
Kim S et al. False-positive rate of a "fourth-generation" HIV antigen/antibody combination assay in an area of low HIV prevalence. Clin Vaccine Immunol. 2010 Oct;17(10):1642-4.
“Among 2,176 participants free of HIV infection [HIV-negative] who received a vaccine product, 908 (41.7%) had VISP [vaccine-induced HIV seropositivity], but the occurrence of VISP varied substantially across different HIV vaccine product types: 399 of 460 (86.7%) adenovirus 5 product recipients, 295 of 552 (53.4%) recipients of poxvirus alone or as a boost, and 35 of 555 (6.3%) of DNA-alone product recipients developed VISP. Overall, the highest proportion of VISP (891/2176 tested [40.9%]) occurred with the HIV 1/2 (rDNA) EIA kit compared with the rLAV EIA (150/700 tested [21.4%]), HIV-1 Plus O Microelisa System (193/1309 tested [14.7%]), and HIV 1/2 Peptide and HIV 1/2 Plus O (189/2150 tested [8.8%]) kits. Only 17 of the 908 participants (1.9%) with VISP tested nonreactive using the HIV 1/2 (rDNA) kit. All recipients of a glycoprotein 140 vaccine (n = 70) had VISP, with 94.3% testing reactive with all 3 EIA kits tested. Among 901 participants with VISP and a Western blot result, 92 (10.2%) had a positive Western blot result (displaying an atypical pattern consistent with vaccine product), and 592 (65.7%) had an indeterminate result. [In summary, positive ELISA testing with positive Western Blot was only considered non-infection due to undetectable viral load, yet many people considered HIV infected also have undetectable viral load]
Cooper CJ et al. Vaccine-Induced HIV Seropositivity/Reactivity in Noninfected HIV Vaccine Recipients. JAMA. 2010 Jul 21;304(3):275-283.
“When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive.”
Shima-Sano T et al. A human immunodeficiency virus screening algorithm to address the high rate of false-positive results in pregnant women in Japan. PLoS One. 2010;5(2):e9382.
“In the final multivariate model, after age, sex, the TPPA [syphilis] test result, and community were controlled for, independent immunological risk factors for false-positive Murex EIA [HIV antibody] results were increasing levels of S[chistosomiasis] mansoni [worm] egg IgG1 and S. haematobium worm IgG1 and an RF titer of 80. In addition, false-positive results were significantly associated with decreasing levels of S. mansoni worm IgG1 and IgG2 and P. falciparum IgG1 and IgG4…there is a need for increased awareness both among public health authorities as well as in individuals of the reality of false positive test results and potential for error in diagnosis…Diagnosing someone as HIV positive has huge implications in medical, psychological and social domains for the individual.”
Everett DB et al. Association of schistosomiasis with false-positive HIV test results in an African adolescent population. J Clin Microbiol. 2010 May;48(5):1570-7.
“A city hospital nearly destroyed a New Jersey woman’s life and wrecked her marriage after misdiagnosing her with terminal HIV, hepatitis and herpes, according to a bombshell lawsuit. Maria Osorio, 54, of Passaic, said…a nurse offered her a free instant cheek swab and blood test [and] she accepted. That’s when she was told she had HIV. “It was horrible. I wanted to throw myself on the subway tracks,” she said. The shocked Osorio immediately turned on her husband of 37 years, Gabriel Lezcano, 60, who works as a janitor in New Jersey. “I started screaming violently at him. I pushed him. I pulled his hair. ‘Who were you with?’ I asked him. He kept denying that he was with anyone, but I kept raising my voice and pushing him. ‘You must have been with someone. You must have had too many beers and maybe now you just don’t remember,’ “ she recalled…A few days later, the hospital called again to say the disease was very advanced, according to court papers. “I wanted to kill him,” she said. “I began to mistrust him and hate him. I couldn’t believe that he had been with other women, that he had lied to me.” She also decided to commit suicide. “I kept thinking how I could kill myself. All I did was plan how I was going to end my life,” she said…She stopped sleeping. She threw up constantly. She couldn’t work. “I didn’t want to get out of bed,” she said. Her husband stopped sleeping, too. They both became addicted to sleeping pills and took to sleeping in separate beds, alone in their misery and distrust. Her two grown sons, who still live in Colombia, were hysterical. They would call, crying, insisting there was a mistake. When Osorio, a home health aide, pointed out to the nurses that she had no medical problems whatsoever, they replied, “This is a silent disease.” “They told me that this machine does not lie,” she said. But almost three weeks later, the hospital called to say she was perfectly healthy…But the damage to the marriage had already been done. “I met him when I was 17 years old. We were always very united as a couple,” Osorio said. “We work and we come home, and that is our life.” Now they still sleep in separate beds, and still rely on pills to sleep. “This has really hurt our marriage. We are afraid to have any sexual contact with each other. We are still very nervous,” Osorio said.”
“A large immunization effort has been under way to accomplish the goal of the Pan American Health Organization of eliminating rubella by 2010, and 3 million people were immunized in São Paulo in 2008. In that year, our blood center in São Paulo, Brazil, experienced an unusual increase in the frequency of blood donors demonstrating falsely reactive tests for human immunodeficiency virus Type 1 (HIV-1). Many of these donations were from people who had recently received the rubella vaccine, and we sought to determine the relationship between rubella vaccination and this problem of false reactivity. HIV-1 infection screening in Brazil is based on the detection of specific antibodies and involves a two-stage process beginning with an enzyme immunoassay (EIA) screening followed by a confirmatory test, Western blot assay (WB). Indeterminate results in WB have been found to be associated with a variety of medical conditions other than HIV and have been attributed to other retroviral infections, cross-reactivity between viral proteins, kit design, assay process, HLA (alloimmunization), and experimental vaccines…21 donors were included in this study because they [were ELISA positive and WB indeterminate and] had also donated before rubella vaccination and the effect of rubella seroconversion could be assessed…100% of the cases compared with 30.0% of controls [donors negative on all viral tests] reported a recent rubella vaccination…We analyzed frozen serum samples from serum library from blood donors before rubella vaccination (A), from the false-positive donation (B), and 5 weeks after donation (C). All samples (A, B, and C) were negative for HIV by reverse transcription–polymerase chain reaction…HIV EIA testing of the C samples demonstrated HIV seronegativity.”
Araujo PR et al. Rubella vaccination and transitory false-positive test results for human immunodeficiency virus Type 1 in blood donors. Transfusion. 2009 Nov;49(11):2516-7.
“Rock wildman OZZY OSBOURNE ravaged his body so badly with drink and drugs, doctors wrongly diagnosed him with Aids. The Black Sabbath frontman was tested for the deadly virus during his heady heyday, and was left in shock when a blood test came back as HIV positive. He tells Britain’s Glamour magazine, “I went to the doctor and had an Aids test and he told me it was positive. “That was one of the worst days of my life.” But after undergoing another blood test, the star was relieved to hear he had been misdiagnosed because of the impact his hedonistic lifestyle had taken on his immune system. He adds, “When I used to f**king get loaded I would get myself into all kinds of situations. “It turned out that because I was drinking and using drugs so much, my immune system had dropped so that it was a borderline result. “When I went back to be tested again it was negative.””
Ozzy Osbourne - Osbourne: ‘Doctors told me I had AIDS’. 2009 Oct 5
“An HIV-positive homeless man convicted of biting a Miami police officer has been sentenced to 15 years in prison…Hall ultimately tested negative for HIV, the virus that causes AIDS, but only after months of taking precautionary medication that caused diarrhea, vomiting and nausea.”
HIV-positive man going to prison for biting police officer. Sun Sentinel (AP). 2009 Aug 27,0,4071445.story
“An HIV-positive man in northwest China’s Gansu province has apparently recovered from the disease, a local newspaper reported today…after taking two packets of a special Chinese medicine each day four years after the diagnosis, Li managed to fight off the disease [i.e. was tested and was found to be HIV-negative]
Report: HIV carrier cured in Gansu. China Daily. 2009 Aug 19
“We found that specificity of the OraQuick ADVANCE with oral fluid declined significantly with 1 month remaining to expiration, leaving little margin for error from other sources.

Facente SN et al. False positive rate of rapid oral fluid HIV tests increases as kits near expiration date. PLoS One. 2009;4(12):e8217.
“Although nonspecific reactvity [false positives] may sometimes be attributed to autoantibodies, it is possible that in some cases the pattern may represent a cross-reaction with another human retrovirus…POSITIVE blot results using any specimen type (serum, plama, or urine) should be followed with additional testing. Such testing may rely on alternative test methods or specimen types. [yet this is a 'confirmatory test'!][Table P shows that 1 out of 63 tests on pregnant women who were HIV ELISA negative was positive on western blot]
Human Immundeficiency Virus type 1 (HIV-1) Western Blot kit. Maxim Biomedical. 2009 Jun 1
“Expert evidence in a case [in Botswana] involving a woman who was wrongly diagnosed with HIV/AIDS has shown that she suffered a post-traumatic disorder. The woman, Kgakgamatso Sekgebetlela, was wrongfully diagnosed with the virus in 2003, which led to her being estranged from her husband and children.”
Keoreng E. Wrong HIV diagnosis traumatised woman - psychologist. MmegiOnline. 2009 May 14
“In the first 7 months after oral fluid testing was introduced, 35 (0.16%) of 21,722 tests were false positive by Western blot, consistent with the 99.8% specificity claim by the manufacturer in the product package insert. However, in October 2005, staff members at the clinics noticed an increase in the number of false-positive oral fluid test results each month. From an average of 5 false-positive tests per month, the monthly number of false-positive tests increased to 11 (0.27% of 4,024 tests) in October 2005 and to 36 (0.97% of 3,735 tests) in November 2005. An investigation detected no consistent relation between false-positive results and test kit handling, storage conditions, or lot numbers or between false-positive results and clinic sites, test operators, or patient characteristics.”
Rothman RE, Kalish B. Update on emerging infections: news from the Centers for Disease Control and Prevention. False-positive oral fluid rapid HIV tests--New York City, 2005-2008. Ann Emerg Med. 2009 Jan;53(1):151-4; discussion 154-6.
“Anti-HIV antibody tests can be falsely positive in SLE [Systemic Lupus Erthematosus] because sera from SLE patients contain antibodies that interact with HIV in western blot analyses. Thus, positive HIV-antibody tests should be confirmed by antigen or nucleic acid detection in the setting of a CTD [connective tissue disease]
Walker UA et al. Rheumatic conditions in human immunodeficiency virus infection. Rheumatology (Oxford). 2008 Jul;47(7):952-9.
“In late 2005, an unexpected increase in the number of false-positive oral fluid tests occurred, but the increase subsided after several months. In December 2005, while the cluster of false-positive oral fluid test results was being investigated, the NYC DOHMH Bureau of STD Control suspended oral fluid testing in the clinics for 3 weeks…In late 2007, another larger increase in the incidence of false-positive oral fluid rapid test results was observed. The cause for the episodic increases in false-positive oral fluid tests has not yet been determined.”
False-positive oral fluid rapid HIV tests – New York City, 2005–2008. MMWR. 2008 Jun 18;57:1-5.
“PCR results were positive for HIV virus in 3 neonates. These infants on follow up were asymptomatic and 4 have been tested at 18 months using HIV ELISA with two different antigen tests and one rapid test to confirm the diagnosis. Surprisingly, all 3 PCR positive neonates were nonreactive to ELISA.”
Agarwal D, Agarwal NR. False positive HIV-1 DNA PCR in infancy. Indian Pediatr. 2008;45:245-6.
“The FPPV [False Positive Predictive Value]…can reach 99.697% in the blood donation population group. In other words, 99.697% of the HIV-Ab[Antibody] positive results may be false-positives in this group. Our surveys also show that, in 1,195,286 sera specimens from the blood donors, 2439 specimens were HIV-Ab positive by third ELISA, and 11 HIV cases were confirmed by WB [Western Blot]. [i.e. a FPPV of 99.5%, assuming that the Western Blot is valid]
Liu P et al. The false-positive and false-negative predictive value of HIV antibody test in the Chinese population. J Med Screen. 2008;15(2):72-5.
“A 33-year-old Caucasian heterosexual woman was found to be HIV positive following investigations in 1991…She initially suffered from an adjustment disorder following the positive diagnosis. From 1993 to 1995 she suffered from depression with hypochondriacal reassurance seeking behaviour with fear of developing AIDS. She experienced rejection in her relationshipand discrimination in her job. She then gradually came to terms with the condition by 1996 and positively adapted her social life, leading to an improved mental state. In 1997 she was re-investigated and found to be HIV negative, at a time when she was attempting to return to paid employment. After an initial couple of weeks of elation following receipt of this information, she developed a depressive episode. This was associated with anger over her predicament and anxiety of losing her newfound social circle which was based around AIDS support groups…A 35-year-old Caucasian gay man was found to be HIV positive on a routine 6 monthly testing in 1996. He had a past history of bulimia nervosa, though his condition was in remission. His job involved direct health care delivery. Following the diagnosis he suffered from depression with suicidal ideation. While struggling to cope, he engaged in risk-taking behaviour (unprotected sex and harmful use of alcohol). He disclosed his HIV status and was moved to a non-patient contact job, which he did not enjoy. In 1999 he was re-tested after no confirmatory test was found in his notes. He was found to be HIV negative. Initial elation and shock soon gave away to low mood, needing treatment with anti-depressant medication. He experienced anger towards perceived wasted time in his life…A 25-year-old heterosexual Asian, who was a victim of torture seeking asylum, was housed with a HIV-positive person, which made him anxious. Testing revealed positive HIV status in 1991. Following the diagnosis he developed depression with obsessive symptoms. This gradually resolved, but in 1993 he married under pressure from family. The marriage broke down within months due to his anxiety of transmitting HIV to his wife. He suffered severe adjustment disorder at this point. He suffered extreme shame and guilt over this ordeal. Thereafter he displayed resilience and reorganized his life and started working with victims of torture. In 1996 he developed a cold, which he believed was sign of imminent AIDS. On seeking medical advice, discrepancies appeared between his history and medical records, which led to retesting. The results confirmed a HIV-negative status. He experienced anger and shock at this development, and regretted loss of years of his life. He developed depression with labile and irritable affect with suicidal ideation and PTSD type ‘re-living’ symptoms of past torture…A 19-year-old woman was diagnosed as HIV positive after travelling abroad in 1989. She had had anorexia nervosa in her adolescence. She developed acute stress reaction with hypochondriacal features, followed by mixed anxiety and depression. She received psychotherapy and treatment with antidepressants. She modified her career choice, presuming a short life expectancy. She remained in a stable relationshipbut experienced sexual dysfunction. She received private care between 1990 and 1999. She was re-tested when she moved to NHS care in 1999 and was found to be HIV negative. She experienced anger and regret for major life decisions and developed Acute Stress Reaction and Panic Attacks. Her relationshipa lso suffered with the change of roles and expectations.”
Byattacharya R, Baron S, Catalan J. When good news is bad news: psychological impact of false positive diagnosis of HIV. AIDS Care. 2008 May;20(5):560-4.
“The study population included all patients seen at the Comprehensive Care Center [in Nashville, Tennessee] from August 1997 until 30 June 2007. Of 4,450 patients referred, 51 were subsequently determined to be HIV-uninfected by undetectable plasma HIV-1 RNA, CD4 positive lymphocyte count within normal limits, and repeat ELISA.”
Maddux DE et al. Misdiagnosis of HIV infection: implications for universal testing. AIDS. 2008 Feb 19;22(4):546-7.
“A farmer in northeast China’s Jilin Province has tested HIV negative, six years after being diagnosed as HIV-positive, according to the provincial Center of Disease Control (CDC). Wen Congcheng, from Erdaogou Village in Chuanying District, Jilin city, first tested HIV positive in 2001 at the Chuanying District disease prevention and control center when it was screening blood-plasma donors. Late in 2003, he was re-confirmed to have HIV/AIDS as a result of another test, this one by the CDC of Jilin province, which tested the same blood sample originally analyzed by the Chuanying District CDC…in July this year, Wen received a negative test result at the No. 1 Clinical Hospital of Beihua University in Jilin…Wen decided to seek another opinion and went to the First Hospital of the China Medical University and another three hospitals for HIV tests, which all proved to be negative…The Jilin municipal CDC carried out a follow-up test which confirmed the negative result, and later the provincial CDC also confirmed the result.…Professor Wu Min, a member of the HIV/AIDS experts’ committee under the Ministry of Health, is sceptical about the validity of the original positive test result…“I can not believe that such miracle could have really happened,” he said. “Some patients appear to be free of the virus after effective treatment, but the HIV antibody is always there, so the test result will still be positive.” [Wen was never treated with antiretroviral drugs]
Chinese farmer cleared of HIV six years after testing positive. China View. 2007 Dec 3
“The table shows the results of the rapid tests for HIV. In the total sample of 1517 tests the three rapid test algorithm had reasonable sensitivity (97.7%, 95% confidence interval 94.1% to 99.4%) and negative predictive value (99.7%), but the specificity was low (90.4%, 95% confidence interval 88.7% to 91.9%) and the positive predictive value was unacceptably low (56.3%). Overall, 129 of 295 positive test results were false positives (43.7%) and four of 1222 negative results were false negatives (0.3%). Of the 129 false positives, 123 (95%) resulted from the Determine and Uni-Gold tests.”
Gray RH et al. Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study. BMJ. 2007 Jul 28;335(7612):188.
“Tommy Morrison had a seemingly boundless future in 1996. A former heavyweight boxing champion, he had had a starring role in “Rocky V” and was in line for his biggest payday, a showdown against Mike Tyson. All that came to an abrupt end, though, when he tested positive for H.I.V…In 1996, he tested positive for H.I.V. These days, he is back in the ring. He fought in West Virginia in February, and his return has raised questions of just how a fighter whose blood tested positive for H.I.V. in 1996 could test clean today.

This year, Morrison took two separate blood tests to support his assertion that he was not infected with H.I.V., West Virginia officials said last week. The test results provide new details on why they licensed him to return to the ring 11 years after he tested positive.

Two nationally renowned H.I.V. experts reviewed those and a third blood test for The New York Times, and said they suggested Morrison had been knocked out of the ring by false positive tests — if, indeed, the new tests are his blood…Morrison, 38, who has often derided conventional views on H.I.V. and AIDS, said he was pleased to hear some experts supported his assertion of a false positive.

“People are starting to wake up,” he said last week in a telephone interview. “There’s been a lot of careers destroyed along the way for no reason. Mine’s certainly been one of them.” The Times obtained copies of three documents, not previously made public, that purport to be tests of Morrison’s blood this year.

One of them, negative for H.I.V. antibodies, was a report from LabCorp in Phoenix on blood drawn Feb. 6 and was released by Peter McKinn, Morrison’s promoter. The second, which did not detect H.I.V. in DNA, was a LabCorp report on blood drawn Feb. 14 and was released by West Virginia. The state used those tests to license Morrison to box, said Michele Duncan Bishop, general counsel for the West Virginia Department of Revenue, which oversees the athletics commission. A third test, from Specialty Laboratories of Valencia, Calif., on blood drawn Jan. 5, indicates Morrison tested positive for H.I.V. antibodies but negative for H.I.V. in RNA. That report was released by Randy D. Lang, Morrison’s former legal adviser, who said the antibody result showed Morrison was still infected. But the experts said the RNA result in the same report raised the possibility that the antibody result was a false positive…The mixed result in the Jan. 5 test makes it “likely that the antibody result is a false positive,” according to Dr. Daniel R. Kuritzkes, a Harvard professor who directs AIDS research at Brigham and Women’s Hospital in Boston and is chairman of the board of the H.I.V. Medicine Association. Kuritzkes reviewed the test for The Times. Without additional blood work, he added in an e-mail message, “it’s hard to know for sure what’s going on, but I suspect he was never H.I.V.-infected.”

Dr. Michael P. Busch, director of the Blood Systems Research Institute and a professor of laboratory medicine at the University of California, San Francisco, said H.I.V. antibody screening was misinterpreted a small percentage of the time. He said the RNA and DNA tests, which measure the virus directly rather than through antibodies, would virtually prove that the person was not harboring even a latent infection. “If those results are really all from this person, I would tell you there is no way this person is infected, so something is wrong with those earlier results,” Busch said. Busch said there was a biological basis for some false positives on H.I.V. antibody tests, which makes some people repeatedly test false positive, although the reasons are not well understood.”

Eligon J, Wilson D. Morrison says error in H.I.V. test hurt career. NY Times. 2007 Jul 22
“patients with visceral leishmaniasis can have false-positive HIV test results. A 32-year-old man was admitted to our hospital because of high fever, night sweats, fatigue, and weight loss over the previous 2 weeks. Physical examination showed enlargement of the liver and spleen…Abundant amastigotes of Leishmania were found in bone marrow smears. A duplicate ELISA, third generation, had results that were positive for HIV. With a working diagnosis of visceral leishmaniasis complicating AIDS, treatment with liposomal amphotericin was started, and CD4+ cell counts, viral load measurements, and other expensive tests were requested. Forty-eight hours later, we were informed that results of a Western blot antibody test for HIV components were negative. The patient was treated with liposomal amphotericin B and had an uneventful recovery. This case illustrates that patients with visceral leishmaniasis can have false-positive HIV test results, and, despite all other clinical evidence suggesting HIV coinfection, diagnosis must be confirmed by Western blot analysis [but there is no way to detect a false-positive Western Blot]
Salinas A et al. Refrain from telling bad news: patients with leishmaniasis can have false-positive HIV test results. Clin Infect Dis. 2007 Jul 1;45(1):139-40.
“From August 2004-June 2005, we investigated a sudden increase in false-positive results occurring in a performance study of OraQuick oral-fluid rapid HIV tests in Minnesota.…The field investigation did not identify a cause for the increase in false-positive oral-fluid results, and the incidence study detected no false-positive results.”
Jafa K et al. Investigation of false positive results with an oral fluid rapid HIV-1/2 antibody test. PLoS One. 2007;2(1):e185.
“The occurrence of these high false-positive rates in M. leprae-infected individuals suggests a possible complication of serodiagnosis of HIV in regions where mycobacterial infections are endemic. There is a need for caution in reporting HIV infection among leprosy patients. Our observations emphasise the value of the various rapid assay kits for HIV, where this false positivity is not observed [but other false positivity is]
Hussain T et al. Serum samples from patients with mycobacterial infections cross-react with HIV structural proteins Gp41, p55 and p18. Lepr Rev. 2007 Jun;78(2):137-47.
“We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome.”
Rolland M et al. Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins. PLoS One. 2007;2(9):e823.
“The [new] Genscreen Plus HIV Antigen–Antibody is an EIA [Enzyme Immuno-Assay or ELISA] for the detection of HIV infection based on the detection (sandwich technique) of antibodies to HIV-1 and HIV-2, as well as the HIV-1 p24 antigen in human serum or plasma. These assays become valuable in diagnosing early HIV infection, reducing the window period by 4–5 days compared with third-generation assays [5]. Genscreen Plus is an assay with enhanced sensitivity for HIV antibody detection that does not differentiate between the antigen and antibody signal…In the first 6 months of its introduction we detected three acute HIV seroconversions in adults who tested antibody negative by the third-generation (antibody only) assays…Using this assay in 18 infants with three consecutive negative HIV-DNA PCR we found that eight were antibody negative (age range 18–24 months), and 10 were positive (age range 19–20 months). Of the 10 infants positive by the fourth generation assay, nine were negative by our previous third-generation HIV assay (performed simultaneously). Repeat fourth-generation EIA testing was negative for nine infants within a few months, confirming waning levels of maternal antibody and not emerging infection. In one infant it was not possible to obtain a repeat sample but it shows no clinical evidence of HIV infection [although a positive HIV test with no symptoms is usually accepted as a genuine infection].”
Nastouli E et al. False-positive HIV antibody results with ultrasensitive serological assays in uninfected infants born to mothers with HIV. AIDS. 2007 May 31;21(9):1222-1223.
“He was positive, then negative, banished from boxing, and now in the middle of a comeback at age 38. The Tommy Morrison story defies logic. But a person who witnessed the first chapter in 1996 is sure of one thing: The HIV test Morrison took 11 years ago was accurate.…After his most recent blood test came back negative for HIV this week, Morrison was granted a boxing license in Texas and was to fight Dale Ortiz on Friday night in Houston. The fight was called off however, because the doctor who examined Morrison failed to file the paperwork with state boxing officials in time. After initially accepting what he called a "death sentence" in 1996, Morrison now believes that the test administered before his bout with Arthur Weathers 11 years ago was a false positive…But the odds of producing an inaccurate HIV diagnosis are very slim, two HIV specialists told…Jalali and Dr. Jeff Kirchner of the American Academy of HIV Medicine said the more plausible scenario in Morrison's comeback is that medicine suppressed his virus to undetectable levels. If Morrison were to go off of those drugs, Kirchner said, signs of the virus in the blood would return "within a very short period of time -- a week, two weeks [but] Morrison has said he stopped taking the medication years ago.…Morrison had several HIV theories in the months before his comeback. He wondered if he tested positive because of steroids, a theory Kirchner said is impossible.”
Merrill E. Morrison’s blood tests still raise questions. ESPN. 2007 Apr 27
“After testing positive five different times, Nakalembe recently tested negative after two confirmatory tests at Mbuya Parish Outreach Clinic. Two initial tests were done at Mulago Hospital and the third at Mbuya Parish Outreach Clinic…Nakalembe tested positive in January 2003 at the age of 12. Her confirmatory test in July 2003, also posted positive…She suffered depression and stigma, failed to get antiretroviral drugs [luckily!] and her mother resorted to buying local herbs for her…when you test positive to a rapid test kit and the confirmatory test posts negative, a third test has to be done. It is called a tie-breaker kit — it resolves the uncertainty. If it turns out negative, then we know that person is negative…Betty Tibaleka, a journalist who hosted Nakalembe on her Untold Story programme on UBC Television recently, says she has had many stories like Nakalembe’s”
Basudde E. HIV negative after five positive results. The New Vision (Uganda). 2007 Apr 3
“In Oregon, it is estimated that 30% of women in labor have not had HIV testing and are candidates for rapid testing. The prevalence of HIV in Oregon is approximately 0.4 out of 1000 women. The sensitivity and specificity of one rapid test are estimated to be 100% and 99.9%, respectively. If all eligible women were screened, the number of false-positive results would be 2.5 times the number of true-positive results, and the positive predictive value would be 29%. The absolute number of false-positive results will increase dramatically if specificity decreases, prevalence is lower, or the number screened increases. Decreasing the specificity to 99.6% would result in the number of false-positive results being 10 times higher than the number of true-positive results, with positive predictive value only 9%. The overall number of positive tests would be low, with the majority being false-positive.”
Guinn D. HIV screening and false-positive results. JAMA. 2007 Mar 7;297(9):947; author reply 948.
“In Oregon, it is estimated that 30% of women in labor have not had HIV testing and are candidates for rapid testing. The prevalence of HIV in Oregon is approximately 0.4 out of 1000 women. The sensitivity and specificity of one rapid test are estimated to be 100% and 99.9%, respectively. If all eligible women were screened, the number of false-positive results would be 2.5 times the number of true-positive results, and the positive predictive value would be 29%. The absolute number of false-positive results will increase dramatically if specificity decreases, prevalence is lower, or the number screened increases. Decreasing the specificity to 99.6% would result in the number of false-positive results being 10 times higher than the number of true-positive results, with positive predictive value only 9%. The overall number of positive tests would be low, with the majority being false-positive.”
Zdeb MS. HIV screening and false-positive results. JAMA. 2007 Mar 7;297(9):947-8; author reply 948.
“Former World Boxing Organization heavyweight champion Tommy Morrison is staging a comeback, saying Tuesday that a positive HIV test that ended his career more than a decade ago was inaccurate. ”I’m negative and I’ve always been negative and that should be the end of it,” Morrison said in a telephone interview with The Associated Press.”
Former heavyweight champ attempts comeback. International Herald Tribune. 2007 Feb 20
“A 33-year old heterosexual man visited the outpatient clinic for sexually transmitted diseases, complaining of scanty, watery, non-purulent urethral discharge, without disuria, that had lasted for one week. There was no significant past medical history…Screening for anti-HIV was performed in a hospital laboratory using two 3rd generation enzyme immunoassays…Abbott assay was repeatedly borderline reactive and Enzygnost clearly nonreactive, the patient’s serum sample was sent to the Slovenian HIV/AIDS Reference Laboratory for confirmatory testing on July 27, 2004…in the Reference Laboratory, both screening assays…were nonreactive, and WB[Western Blot]-based confirmatory test…was negative, while the IB[immunoblot]-based confirmatory assay…tested HIV-1 positive.”
Seme K et al. False-positive result of a confirmatory human immunodeficiency virus line immuno assay in an apparently healthy individual--a case report. Coll Antropol. 2006 Dec;30 Suppl 2:43-6.
“Kenyan women who received prophylactic tetanus toxoid injections during pregnancy are 1.89 times more likely to be HIV-1 seropositive than women who did not receive this vaccination…The results are consistent with health care being a very important vector for HIV in sub-Saharan Africa [but they are also consistent with tetanus vaccinations directly generated antibodies that are misinterpreted as 'HIV']
Deuchert E, Brody S. The role of health care in the spread of HIV/AIDS in Africa: evidence from Kenya. Int J STD AIDS. 2006 Nov;17(11):749-52.
“The patient was a 28-year-old male who was referred for HIV testing after a needle stick injury from a needle contaminated by blood from a newly diagnosed HIV-positive patient. He was given postexposure prophylaxis consisting of zidovudine, lamivudine, and nelfinavir for 4 weeks. Baseline and 6-week HIV-1/2 antibody enzyme immunoassay (EIA) testing produced negative results. An HIV viral load assay was ordered at the same time as the 6-week EIA, for which the patient’s blood was collected in a Greiner K2 EDTA tube. This tube was centrifuged and then frozen at 70C within 65 min of collection. The following day, the Versant HIV-1 RNA 3.0 bDNA assay was performed according to the manufacturer’s instructions, using the Bayer System 340 analyzer, and produced a result of 955 copies/ml. No error code was generated by the analyzer during this test. Immediately after this test was performed, a Bayer technician examined the analyzer by prior arrangement (see below). It was discovered that the read head of the instrument was not adequately compressing the tops of the sample wells, potentially resulting in light leakage between wells. Maintenance was performed to correct this problem. A repeat viral load bDNA assay on the same serum 2 days later produced a result of 75 copies/ml. Additional EIAs performed 3 days and 45 days after the initial viral load assay were repeatedly negative (7 and 12 weeks following the needle stick exposure). An additional viral load assay using new serum collected 2 days after the first viral load also produced a result of 75 copies/ml. In the 4.5 months since the needle stick exposure, the patient continues to be asymptomatic, with negative HIV testing, and is presumed to be HIV negative.”
Marinovich A et al. False-positive result from a Bayer Versant human immunodeficiency virus type 1 branched-DNA viral load assay, with a possible role for light leakage after inadequate maintenance of the analyzer. J Clin Microbiol. 2006 Nov;44(11):4288-9.
“We evaluated two HIV enzyme immunoassays (EIAs) by testing 1,965 Ugandans with malaria. We found poor positive predictive values (53% and 76%), particularly with younger age. Combining EIAs eliminated false positives but missed 21% of true positives. Performance of HIV EIAs in malaria may be unsatisfactory.”
Gasasira AF et al. False-positive results of enzyme immunoassays for human immunodeficiency virus in patients with uncomplicated malaria. J Clin Microbiol. 2006 Aug;44(8):3021-4.
[on an HIV test consent form] This test will tell if I have antibodies to HIV. Having antibodies, and therefore a positive test, does not mean I have AIDS or that I will necessarily get AIDS or any other disease…Like many things, the tests are not perfect…Sometimes the tests may be positive even if I do not have the infection because the test are complex and simply not perfect. This is called a"false positive." My health care professional will explain these facts to me and will advise me and offer me more counseling if the result is positive…The social risks of a positive test [whether true or false positive] are that I may be thought to be infected and I could be turned down for life or health insurance, housing, a job, or school even though such kinds of discrimination may be wrong or illegal”
University of Michigan Hospitals HIV test consent. University of Michigan. 2006 Jul 8 [accessed]
“In late 2005, counselors at several HIV testing programs (mainly in New York City and San Francisco) reported an unusually high number of false-positive results from the OraQuick Advance Rapid HIV-1/2 Antibody Test with oral fluid (ACC Jan 4 2006). Since then, CDC investigators have analyzed data from four prospective studies that involved simultaneous testing of whole blood and oral fluid between 2000 and 2005 [Abstract 34LBb]. They found that the specificity of OraQuick was 99.9% with whole blood and 99.6% with oral fluid; in comparison, the specificity of serum EIA was 99.7%. These data suggest that the specificity of HIV rapid testing is slightly lower with oral fluid than with whole blood, but is still well above the FDA minimum threshold (98%) for both specimen types. At three testing sites, the excess number of false-positive results appeared to be related to unidentified host- or site-specific factors; CDC investigators found no evidence of a lot- or device-related problem. Investigators also evaluated an algorithm that was adopted in New York and San Francisco in late 2005. According to this algorithm, a positive result on an oral-fluid rapid test should be followed up with a whole-blood HIV rapid test using a fingerstick. When this algorithm was used, positive results from both oral fluid and fingerstick were almost always followed by a positive Western blot result, whereas a positive result from oral fluid followed by a negative fingerstick was almost always followed by a negative Western blot result. These data suggest that performing a fingerstick test after a reactive oral-fluid test might reduce the number of people who receive false-positive results. However, confirmatory testing is still required for all reactive rapid tests.”
del Rio C. Report from the 13th retrovirus conference. AIDS Clin Care. 2006 Apr;18(4):39.
“Six weeks after an occupational needle-stick injury, a 35-year-old man presented to a clinic in the Los Angeles area for testing to rule out acute infection with the human immunodeficiency virus (HIV). The patient had no other risk factors for HIV infection and reported having had no symptoms suggestive of an acute retroviral syndrome. His recent medical history was notable only for his having received an influenza vaccination 11 days before presentation…an enzyme immunoassay [ELISA] for HIV type 1 (HIV-1) was repeatedly reactive, and the result on a Western blot assay that was performed as part of the clinical protocol to confirm a reactive enzyme immunoassay was indeterminate, with a single band that was positive for glycoprotein 160 (GP160)…it is very important to remind patients and clinicians that influenza vaccination may cause cross-reactivity with HIV antibody assays. The time course for such crossreactivity remains uncertain.”
Erickson CP et al. Influenza vaccination and false positive HIV results. N Engl J Med. 2006 Mar 30;354(13):1422-3.
“A recent surge in false positive results produced by a much-heralded oral HIV test has caused at least six testing sites in Los Angeles, San Francisco and New York to shelve the test and prompted an inquiry by federal health agencies”
Lin II R-G, Chung J. More sites drop oral HIV test. Los Angeles Times. 2005 Dec 20
“in late 2005, HIV testing programs in multiple U.S. cities experienced apparent clusters of false-positive rapid HIV test results using oral fluid (but not whole blood) specimens. Counselors at these programs have expressed concern regarding the specificity and positive predictive value of the oral fluid rapid HIV test.”
Supplemental testing for confirmation of reactive oral fluid rapid HIV antibody tests. MMWR Dispatch. 2005 Dec 16;54.
“Health officials in New York and San Francisco said yesterday that a widely used rapid test for the virus that causes AIDS had been producing too many false-positive results…The test, called the OraQuick Advance H.I.V. test, is the same one the Food and Drug Administration has said it will consider approving for sale to the public for home use without a prescription. In New York, Dr. Susan Blank, an assistant health commissioner, said that city clinics performed 3,600 to 3,700 tests for the virus, H.I.V., each month, largely using OraQuick, and until recently they had about five false positives a month, a rate well within the maker's prediction. But in November, Dr. Blank said, the number shot up to 30, which was cause for concern…In San Francisco, Teri Dowling, manager of H.I.V. counseling and testing for the public health department, said the number of false positives there seemed to rise sharply in May. In 2005, 9,400 tests were done, and 250 were positive. Of those, 49 appeared to be false positives, though not all have yet been confirmed…Douglas A. Michels, president and chief executive of OraSure, said that over all the test was more than 99% accurate. In the last year, the company received complaints of only 107 false positives out of 28,436 tests, Mr. Michels said.”
“Health officials in New York and San Francisco said yesterday that a widely used rapid test for the virus that causes AIDS had been producing too many false-positive results…The test, called the OraQuick Advance H.I.V. test, is the same one the Food and Drug Administration has said it will consider approving for sale to the public for home use without a prescription. In New York, Dr. Susan Blank, an assistant health commissioner, said that city clinics performed 3,600 to 3,700 tests for the virus, H.I.V., each month, largely using OraQuick, and until recently they had about five false positives a month, a rate well within the maker's prediction. But in November, Dr. Blank said, the number shot up to 30, which was cause for concern…In San Francisco, Teri Dowling, manager of H.I.V. counseling and testing for the public health department, said the number of false positives there seemed to rise sharply in May. In 2005, 9,400 tests were done, and 250 were positive. Of those, 49 appeared to be false positives, though not all have yet been confirmed…Douglas A. Michels, president and chief executive of OraSure, said that over all the test was more than 99% accurate. In the last year, the company received complaints of only 107 false positives out of 28,436 tests, Mr. Michels said.”
“A MAN who tested positive for HIV, the virus that causes Aids, has subsequently shown up negative for the disease in a case that has mystified doctors…Stimpson was tested three times in August 2002 at the Victoria clinic for sexual health in central London and the results showed he was producing HIV antibodies to fight the disease…In October 2003, after impressing doctors with his good health, Stimpson was offered a new test, which came back negative. Further tests in December 2003 and March last year also proved negative.”
Kirkham S. Doctors baffled as HIV man 'cures' himself. The Sunday Times. 2005 Nov 13,,1-523-1870340-523,00.html
“A Texas woman won a civil suit against a Houston-area hospital Wednesday that she said wrongly diagnosed her as HIV-positive when she was about to give birth…Johnson claimed Methodist Hospital incorrectly diagnosed her with the virus when she was 8 months pregnant…"I felt like my whole world was crashing down," Johnson said. "I was scared for my children. I was scared for my husband. I didn't know if the baby was HIV-positive. I cannot tell you the emotions that went through my head."…she went into premature labor within 24 hours of hearing the news…Doctors and nurses pumped Johnson and her newborn son with drugs used to treat HIV…Her attorney, Stephen Buttram, said the lab technician did not properly label her blood sample…Johnson said doctors have told her that there is no conclusive proof that the heavy treatments her son was on will have any effect on him.”
Jurors find Texas hospital negligent in HIV misdiagnosis. 2005 Aug 25
“A 31 year old British heterosexual man attended the genitourinary medicine clinic requesting an HIV test. His last sexual contact was 3 weeks earlier with a female partner of 3 months. He had recently learnt that she had had a previous male partner who had had African sexual partners and therefore may be at higher risk of having HIV infection. He obtained a home HIV test kit from a Canadian based internet site and this result was positive. On further inquiry he gave a history of sore throat and swollen cervical lymph nodes 2 months previously, although these symptoms had largely resolved. He had never tested for HIV before and had no other significant risk factors. We requested an HIV test on the patient; the result was negative. We repeated the test after 3 months and again it was negative”
Haddow LJ, Robinson AJ. A case of a false positive result on a home HIV test kit obtained on the internet. Sex Transm Infect. 2005 Aug;81(4):359.
[South African] Zandile Magudulela had her world turned upside down when she was told mistakenly by nurses at KwaMashu PolyClinic that she was HIV-positive. She immediately contemplated suicide, but tests later showed that she did not have the virus. The KwaMashu woman was mistakenly treated as an HIV patient for more than six months. Married for nearly 20 years, Magudulela told the Daily News that she had been on the verge of committing suicide when she was told she was HIV- positive and that the medicine she used for more than six months was administered to HIV patients. A doctor, who wanted to remain anonymous, confirmed that Trimoxazole tablets [a potent 'sulfa' antibiotic], which were given to Magudulela, were mostly used by HIV patients who have a low CD4 count to prevent them from developing pneumonia.”
Mthembu B. Woman treated for HIV by mistake. Daily News (South Africa). 2005 Jul 11
“Recently a lady aged 32 in her second pregnancy tested HIV antibody positive by the ELISA (enzyme-linked immunosorbent assay) screening test, but negative by the Western Blot assessment, which is a definitive confirmatory test, except if one is infected with HIV during the 3-month window period. That approximately 1.26% of ELISA tests give positive results which are proven false by the Western Blot is well documented in literature, which should be noted by medical practitioners and labs in the country that conduct screening tests in order to counteract traumatic social impasse. ELISA can be HIV antibody false-positive in the uninfected for several reasons, because each individual in life is exposed to plethora of foreign antigens which can initiate poorly-understood cross-reactions; these include, among others, naturally occurring antibodies, autoimmune disease (e.g. SLE and rheumatoid arthritis), pregnancy in multiparous women, TB and leprosy, malaria, Flu and upper respiratory infections, blood transfusions, 13% of alcoholics with hepatitis, liver diseases, 4% of hemodialysis patients and 19% of those with hemophilia, or noteworthy, even following recent vaccinations for hepatitis B, tetanus, rabies and influenza”
Abdulla EM. False-positive HIV test. J Pak Med Assoc. 2005;55:130.
“The patient was diagnosed as HIV antibody positive (ELISA and WB) in 1995 during blood donation…two years later pericarditis was diagnosed and HIV viral load at that time was 29,000 and 24,000 copies/ml. CD4+ cell count was 856 cells/ml. HAART was initiated, and 4 months afterwards viral load became undetectable, CD4+ cell count was unchanged and pericarditis disappeared. Three years after initiating HAART, HIV antibody test was taken for enrollment to a clinical study, and was found to be negative. Since viral load measurements were undetected and CD4+ cell counts were high consistently, HAART was withheld…During the four years after stopping HAART, HIV antibody test remained negative, viral load is undetectable, HIV RNA is negative and viral cultures of blood and semen are negative.”
Levy I et al. Negative HIV antibody test and negative viral RNA in a patient with documented HIV infection. 12th Conference on Retroviruses and Opportunistic Infections. 2005 Feb 22-25
“HIV EIAs have become increasingly more sensitive and specific since HIV testing began in the early 1980s…The small disadvantage of such a highly sensitive test is that the test produces false positives, the number and type of which vary with the assay used and the HIV prevalence in the tested population.”
Fearon M. The laboratory diagnosis of HIV infections. Can J Infect Dis Med Microbiol. 2005 Jan;16(1):26-30.
“The medical records of all rapid HIV-ELISA-positive gravidas [pregnant women] that delivered at our hospital between January 2000 and October 2001 were retrieved…The results of the Western blot tests were also retrieved and correlated to the ELISA results, across varying maternal characteristics.…A total of 69 patients had a positive rapid HIV-ELISA out of 9,781 deliveries. Of those, 26 were confirmed as HIV infected by Western blot (overall HIV prevalence: 0.27%, ELISA-positive predictive value: 37.7%). The subgroup prevalence of HIV and positive predictive value of ELISA were 1.53 and 75% among Caucasians; 2.43 and 82.6% among African-Americans; and 0.05 and 9.8% among Hispanics, respectively (p<0.05 for the comparisons between Hispanics and non-Hispanics only)…The positive predictive value of rapid HIV-ELISA during pregnancy varies widely, depending on maternal race/ethnicity and sexual behavior. The routine disclosure of rapid intrapartum HIV serum screening results prior to Western blot confirmation should be avoided in very low-risk populations.”
Zacharias NM et al. High false-positive rate of HIV rapid serum screening in a predominantly hispanic prenatal population. J Perinatol. 2004 Dec;24(12):743-7.
“In our study we had a very high incidence of false positive HIV DNA PCR (75%) especially in younger infants”
Shah I. Diagnosis of perinatal transmission of HIV-1 infection by HIV DNA PCR. 2004 Oct-Dec;6(4):187-189.
“Nearly eight years ago, just after Christmas in 1996, I tested H.I.V.-positive while I was on vacation in Los Angeles…it didn't surprise me when it did. My partner had passed away from AIDS. Before that I had been partying for about -- well, I'll be 60 on the 4th of July, so you do the math…I took the test results back home to Hayward, Calif., and gave them to my doctor at the V.A. clinic. He treated me for H.I.V. for the next seven and a half years. In July of this year, the V.A. [Veteran's Administration] clinic called because its new computer software had flagged my record for a missing diagnosis. I was asked to come in for another H.I.V. test. I found out that I was in fact negative and apparently had never been positive…I had been seeing my doctor for at least a decade for a bad back, a heart condition, ulcers, and I always trusted him. If he had said the sky was purple with pink polka dots, I would have had no reason to question him. The V.A. clinic eventually did another H.I.V. test. It was negative, but no one told me…I started telling my friends about my diagnosis because I'd had sexual relationships with many of them. At first, I still dated: dinner, a show, a bar, but the evenings always ended there. The minute I'd say I was positive it would be: ''It's late. I have to get up early for work.'' I started accepting that. Eventually I completely shut off…My big fear was that I'd have to die by myself. I tried to keep people around, even if it was as close as the telephone. People bailed out who at first said they were my friends and would always be there…I had the symptoms of AIDS -- weight loss, diarrhea, no appetite, vomiting. They call it being psychosomatic. I knew about the symptoms from my own lovers, from being right there, from cleaning up the mess…The eight years I thought I was positive cost me more than 45 pounds. I take medicine for depression and stress, even now…Two months after [my father] died, I found out I was negative. My doctor wrote me a letter saying he took full responsibility. It was human error. My lawyers filed a claim, and now we have to wait to see what happens. For years, I received free meals, help with rent, free counseling and therapy from AIDS organizations. It's going to be very tough financially now, but the relief is worth it. It feels as if somebody took an anvil off my shoulders. I'm planning trips. I haven't felt this good in 30 years, but that doesn't mean I'm not still mad as hell.”
Malone J, Williams P. A detour before dying. NY Times. 2004 Oct 10
“The currently used laboratory based and rapid HIV-tests show intolerably high numbers of false positive results when used in developing countries. This is mainly due to interfering effects of diseases virtually absent in developed countries. If this becomes widely known, such information could destroy the whole concept of the Knowledge Protects Program. People will prefer to seek refuge in the belief that they are among the 'false positives'. Therefore, it is not only an ethical but also a practical requirement for the success of the program that the reliability of the rapid tests being used is identical or even superior (i.e. more forgiving against handling errors) than those tests used in the developed world. Fortunately, such test systems have recently been introduced to the market. [by us!!] 2004 Sep [accessed]
“For eight years, Hayward resident Jim Malone attended biweekly counseling sessions for men living with HIV…He had been told in 1996 that he was HIV-positive. Earlier this month, Malone, 59, was summoned to his doctor's office. He listened as the doctor delivered the stunning news: He is HIV negative…Malone had arrived at the clinic in 1996 with lab results from an outside testing firm in Southern California. Those results showed he was HIV positive. The VA did its own confirmatory HIV test on Malone and found he was negative [but due to a list of mixups did not inform him for another 8 years]
Guthrie J. False diagnosis of HIV discovered after 8 years: Veteran's life severely affected after VA doctor made mistake. San Francisco Chronicle. 2004 Aug 28
“A Tanzanian man, who claims a wrong HIV diagnosis wrecked his wedding, has sued the hospital responsible for $50,000. Ramadhani Kaya was about to go on his honeymoon when he received his positive tests results. Mr Kaya, who says he is a very 'religious' man and could not have HIV/Aids, retook the test three times elsewhere with negative results. But his wife's family did not believe the new results and she returned to stay with them.”
Ntetema V. 'HIV groom' sues Tanzania hospital. BBC. 2004 Aug 5
“34 women tested HIV-1 positive with both rapid test and EIA, and all were confirmed by Western blot. There were 4 false positive and non false-negative rapid test results…positive predictive value [of the rapid test] was 90% [i.e. 10% of positive results were false]…The EIA had 11 false-positive results: 5 in women with an indetermineate Western blot result (usually a single p24 band) and 6 others with negative Western blot results.”
Bulterys M et al. Rapid HIV-1 testing during labor: a multicenter study. JAMA. 2004 Jul 14;292(2):219-23.
“Specificity [of this HIV test] is based on assay of blood donations from random donors [under the assumption that any positive result would be a false positive, yet when this test is used under normal circumstances such a positive would be treated as a true positive]…Specificity based on an assumed zero prevalence of antibody to HIV-1 and/or HIV-2 in random donors (17037 out of 17054) is estimated to be 99.90%…[but] in these calculations, one sample of the eighteen total repeatedly reactive specimens was confirmed by Western Blot and has been excluded…[Table II shows that out of 27 initially reactive test results from blood and plasma donors, only 18 were repeatedly reactive]
Human immunodeficiency virus types 1 and 2: (E. coli, B. megaterium, recombinant antigen) HIVAB HIV-1/HIV-2 (rDNA) EIA. Abbott Laboratories. 2004
“False Positive Results…Reocgnized Problems…1. HLA-antibodies [e.g. women with a prior pregnancy]…2.Repetitive Freeze/Thaws 3. Other retroviruses 4. Heating of sera 5. Autoantibodies…6. Hypergammaglobulinemia…7.Cross-reactive proteins…8.Non-specific IgM binding (e.g. after vaccination…)”
Wormser GP (ed). AIDS and other manifestations of HIV infection. Academic Press. 2004
“A patient developed end-stage renal disease…He subsequently had human immunodeficiency virus (HIV)-1 antibody screening performed as part of a pre-transplant evaluation. The HIV-1 enzyme immunoassay (EIA) antibody test was repeatedly reactive. The HIV-1 western blot was indeterminate. The western blot pattern revealed "non-specific staining obscuring bands in that region." Another sample of serum was sent and the results were identical to the first result. An HIV-1 proviral qualitative polymerase chain reaction test was then performed several months later and no HIV-1 DNA was detected. One year later, an HIV-1 RNA test was negative…Throughout this period and thereafter, the patient has exhibited no symptoms of HIV infection.”
Silverstein DM et al. False-positive human immunodeficiency virus antibody test in a dialysis patient. Pediatr Nephrol. 2004 May;19(5):547-9.
“Dimitrios Garnelis and his wife, Laura, sued the [Indiana, USA] Department of Health because of a false-positive test result Garnelis received in 1991. Until he was on a visit to Greece in July 1999, where health officials retested him before prescribing treatment, Garnelis lived under the impression that he was HIV-positive…Separately, the Garnelises also have filed complaints against the Bell Flower Clinic, 1001 W. 10th St., Indianapolis, where Dimitrios Garnelis had his blood drawn for the initial test, and a physician.”
Penner D. Appeals court lets man sue state over false HIV test result in 1991. Indianapolis Star. 2004 Apr 22
“When submitted to ELISA, 0.26% of [41,059 blood] samples [from people considered healthy and not at risk] were positive; 57.4% of those were considered HIV false-positive after the confirmatory WB tests were performed, for a final prevalence of 0.11% of HIV seropositivity for that population. More interesting was finding that 4.8% of the false-positive results were due to T cruzi infection, according to Abbott Chagas Antibody EIA”
Parra-Piñeros JE et al. False-positive human immunodeficiency virus test and Trypanosoma cruzi infection in eastern Colombia. South Med J. 2004 Apr;97(4):423-4.
“Natural antibodies (NAb) are those that are present in the serum of healthy individuals in the absence of deliberate immunization with the target antigen. The importance of NAb reactive with self-antigens has long been neglected…However, it is now well established that autoreactive antibodies and B and T cells are present in healthy individuals, and that autoreactive repertoires are predominantly selected during fetal life [Consider what would happen if some of these naturally occurring ‘polyreactive’ antibodies reacted with the HIV proteins in an HIV antibody test! Yes, you would have a false positive.]
Varambally S et al. Natural human polyreactive IgM induce apoptosis of lymphoid cell lines and human peripheral blood mononuclear cells. Int Immunol. 2004 Mar;16(3):517-524.
“A cross-sectional study was conducted from January--December 1999 as screening of voluntary non-remunerated blood donor pool for HIV in the public sector blood banks, in all the six divisions of Balochistan. 5000 subjects were screened for the presence of antibodies against HIV-1/2. The subjects were all males between the age group 18-50 years…Strategy I was a rapid test and was performed on Capilus HIV I/2 by Cambridge, Ireland. Strategy II (ELISA) was performed on Lab System HIV I/2 Finland and Strategy III (ELISA) was undertaken as a confirmation test performed on Sanofi Pasture HIV I/2 France…Out of 5000 subjects, 48 (0.96%) were positive for HIV-1/2 on Strategy I, 37 (77% of 48) met the criteria of false positive, while only 11 (0.22% of 5000) were found to be true positive”
Sheikh AA et al. High frequency of false positive results in HIV screening in blood banks. J Ayub Med Coll Abbotabad. 2004 Jan-Mar;16(1):28-31.
“Using immunoblotting to test the sera of 257 humans for antibodies of four isotypes (IgG1, IgM, IgA, and IgG4) to the BLV [Bovine Leukemia Virus] capsid antigen (p24), we detected at least one antibody isotype reactive with BLV in 74% of the human sera tested. The specificity of the reactivity was strongly suggested by competition studies and by ruling out cross-reacting antibodies to other chronic human viruses [studies that would not normally be done if p24 was found in a human]
Buehring GC, Philpott SM, Choi KY. Humans have antibodies reactive with Bovine leukemia virus. AIDS Res Hum Retroviruses. 2003 Dec;19(12):1105-13.
“The overall specificity of the Reveal™ Rapid HIV -1 Antibody Test for serum specimens in these studies was calculated to be 3608/3639 = 99.1%, combining the number of Reveal™ Rapid HIV -1 Antibody Test Non-Reactive results obtained from the study of previously screened HIV -1 antibody negative serum specimens with the number of Reveal™ Rapid HIV-1 Antibody Test Non-Reactive results obtained from the studies of high-risk populations [i.e. 1% false positives if we can assume that other antibody tests (ELISA and Western Blot) are 100% accurate and also completely independent from this rapid test]…The overall specificity of the Reveal™ Rapid HIV -1 Antibody Test for plasma [i.e. blood] specimens in these studies was calculated to be 2970/3011 = 98.6% [i.e. 1.4% of tests false positive] combining the number of Reveal™ Rapid HIV -1 Antibody Test Non-Reactive results obtained from the study of previously screened HIV -1 antibody negative plasma specimens with the number of Reveal™ Non-Reactive results obtained from the studies of low -risk populations [with the same caveats]Antibody detection tests for HIV -1/HIV -2 antibodies provide a means to aid in the diagnosis of HIV -infected individuals. However, when utilizing HIV antibodies to diagnose HIV infection, corresponding clinical factors must also be considered…”
Reveal rapid HIV-1 antibody test. MedMira. 2003 Dec 4
“A Muslim couple is suing the department of health in the Western Cape for R5-million [about US$750,000] after their baby daughter became infected with HIV under mysterious circumstances at one of two leading paediatric hospitals…The parents, who are both HIV-negative, say…that their three-year-old daughter contracted the virus either at Mowbray Maternity hospital, where she was born, or at the Red Cross Children's hospital, to which she was transferred for surgery. [the possibility of a false-positive HIV test is not considered]…'Baby A', as the papers refer to her, is one of 14 children, all with HIV-negative parents, documented by the March 2004 South African Medical Journal as having contracted unexplained HIV infections in hospitals.”
Deane N. Parents sue health department. Mail & Guardian. 2003 Sep 4
“CASE 1: A 39-year-old married man presented to the Public Health-Seattle & King County sexually transmitted disease clinic in September 2000, seeking HIV serologic [antibody] testing. He gave a history of occasional orogenital sex with other men but denied insertive and receptive anal sex…His ELISA and Western blot results were interpreted as positive…He notified his wife of the result, revealed to her and to [others] that he had had sexual activities with other men, and sought spiritual counseling. However, further evaluation revealed an undetectable plasma HIV RNA level and a reasonably normal CD4+ lymphocyte count. Repeat HIV ELISA testing was negative in October 2000 and in January 2001. The patient expressed substantial distress and required repeated reassurance and psychological counseling. CASE 2: In October 2000, a 23-year-old woman sought HIV testing…because of vaginal irritation, a white discharge, pelvic pain, and fear that she had acquired a sexually transmitted disease. She reported having had multiple male sex partners in her teens, that she usually used condoms, and had been in a monogamous heterosexual relationship for 3 years before testing. The positive HIV ELISA result with Western blot confirmation was followed by findings of an undetectable HIV RNA level and a reasonably normal CD4+ lymphocyte count…In October 2001, after…confirmatory testing, her HIV ELISA results were negative, a result also found in March 2002. The patient described confusion, concern, and relief as well as uncertainty about which providers and test results to trust.”
Wood RW et al. Two "HIV-infected" persons not really infected. Arch Intern Med. 2003 Aug 11-25;163(15):1857-9.
“In a bizarre saga [in Soweto, South Africa] that has baffled medical doctors, an East Rand couple has a baby who has been diagnosed HIV-positive, while both parents have consistently tested negative…Doctors are baffled as to how the child got infected [and they would never consider the possibility of a false-positive test result]. One of them, Dr Johan Pretorius, a paediatrician who tested both the child and parents, said it was a mystery how and where the baby could have contracted the virus…"The parents are absolutely negative. I made tests on them after the baby was diagnosed and they are HIV-negative," he said…According to the parents, their son was born healthy, weighing 2,8kg. "He was growing well and his immunisation chart was satisfactory. He then developed flu symptoms and we took him to the hospital, where he was diagnosed with Bronchitis," the baby's father said…The baby's health started deteriorating and the parents decided to take him to Botselong Hospital, in Vosloorus on the East Rand, in July 2002. It was there that they were told that the baby had HIV symptoms [but, in Africa, fever, cough and diarrhea are taken as signs of AIDS].”
Mabena K. HIV-positive infant baffles doctors after parents test negative. Sowetan. 2003 Jan 8
“Mannose-binding lectin (MBL) is a C-type lectin effector molecule of the innate immune system. MBL is a serum protein of hepatic origin that binds to carbohydrates on microorganisms and plays a role in their clearance and destruction through complement activation and also by inducing opsonization. 11,12 MBL binds with the highest avidity to organisms with many repeating sugar groups and shows selectivity for sugars including mannose and N-acetylglucosamine. Median serum levels of MBL in healthy individuals are approximately 1–2 mg/ml and the levels increase during the acute phase response by as much as 3-fold.13,14 Several studies show that MBL binds to HIV-1 suggesting that MBL plays an in vivo role in opsonizing or neutralizing HIV [meaning that this natural compound would react as a gp120 antibody, resulting in false positive antibody test results in people with high levels]
Hart ML et al. High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1. AIDS Res Hum Retroviruses. 2002 Nov 20;18(17):1311-7.
“A small but significant number of donor sera (0.1-0.3%) yield false-positive results in EIA, and these donors must be permanently deferred from the blood donor list, causing operational and public relations problems [This assumes that the Western Blot is completely accurate, as someone who was also false positive on Western Blot would be categorized as true positive]…In Canada, about 500 blood donors per year are found to have false-positive results in an HIV-1 and -2 EIA [i.e. repeatedly reactive on 2-3 EIA antibody tests but indeterminate on a single Western Blot]. Deferral of blood donors based on this criterion makes donor counseling extremely difficult, especially for regular donors. In addition, our inability to provide a scientific explanation to RR [repeatedly reactive]-but-uninfected donors concerning the cause of the false reactivity in EIA can be a source of great concern and anxiety to these individuals and their family…the SCN-EIA [a modified EIA antibody test that supposedly reduces non-specific reactivity] produced negative results for 69% of the 435 previously screened HIV RR blood donor sera without affecting the positive results of the five HIV confirmed-positive sera in the panel…In the past 10 years, several thousands of blood donors have been deferred [blocked from donating blood] in Canada because of false-positive reactivity in one of the EIAs used to detect exposure to viruses.”
Bouillon M et al. Reduced frequency of blood donors with false-positive HIV-1 and -2 antibody EIA reactivity after elution of low-affinity nonspecific natural antibodies. Transfusion. 2002 Aug;42(8):1046-52.
“In Canada, about 500 blood donors per year are found to have false-positive results in an HIV-1 and -2 EIA…The logical explanation for the false-positive reactivity in the HIV-1/2 EIA is the binding of natural nonspecific polyreactive [antibodies] to the EIA plates…The cut-off values of EIAs are routinely determined by testing thousands of seronegative individuals and large panels of seropositive individuals [but people are 'seronegative' because they are below the current cutoff and 'seropositive' because they are above, so this is really a tautology, assuring at most that new tests are consistent with old tests]…it should be remembered that under current regulations, all donors with a RR [repeatedly reactive] EIA result are permanently deferred from the active blood donor list even if most of them (98.8% in our panel of 440 sera) are found negative or indeterminate in confirmatory testing [Western Blot]
Bouillon M et al. Reduced frequency of blood donors with false-positive HIV-1 and -2 antibody EIA reactivity after elution of low-affinity nonspecific natural antibodies. Transfusion. 2002 Aug;42(8):1046-52.
“Monoclonal antibodies used in diagnostic assays are produced using animal cells, usually from mice. The Achilles heel of this apparently highly specific assay principle is that many individuals, possibly up to 40% of the general population, possess naturally occurring antibodies to animal immunoglobulins (eg, to mouse, rabbit, cow, rat, goat), termed heterophilic antibodies. If an individual with heterophilic antibodies against mouse immunoglobulins has a test by an immunoassay that uses mouse monoclonal antibodies, then the heterophilic antibodies can also form links between the capture and signal antibodies, generating a false-positive signal”
White GH. Trusting numbers: uncertainty and the pathology laboratory. Med J Aust. 2002 Aug 5;177(3):153-5.
“A total of 884 SUDS tests were performed on source patients after occupational exposures (883 negative results, 1 reactive result). The results of repeat SUDS testing on the reactive specimen were also reactive, but the results of enzyme immunoassay and Western blot testing were negative. A new specimen from the same patient showed a negative result on SUDS testing. This suggested a specificity of 99.9%. In the 4 months after SUDS testing was suspended, there was 1 false-positive result on enzyme immunoassay for 1 of 132 source patients (presumed specificity, 99.2%). CONCLUSION: Use of the SUDS test facilitated rapid and accurate evaluation of source specimens, obviating unnecessary prophylaxis. [there was only one positive result and it was later found to be false and it’s a good test?]
Salgado CD et al. Low rate of false-positive results with use of a rapid HIV test. Infect Control Hosp Epidemiol. 2002 Jun;23(6):335-7.
“The first patient was a 40-year-old, previously healthy man who was admitted with a 2-week history of right upper quadrant pain, fever, and malaise. Liver function tests showed acute hepatitis…he admitted having unprotected sexual intercourse with a new female partner 4 months before the onset of jaundice. HIV serology, which was performed after informed consent was obtained, was positive by ELISA. Confirmatory tests with Western blot and p24 antigen, however, were negative…The patient had a persistently positive HIV ELISA, with negative HIV Western blots and HIV p24 antigen at 3, 7, and 12 months after the initial presentation…The second patient was a 58-yearold man who had chronic hepatitis B infection and who was admitted because of liver failure and encephalopathy…While being evaluated for liver transplantation, he was found to be positive for HIV by ELISA. Confirmatory tests with Western blot and p24 antigen were negative…the decision for transplantation was delayed while awaiting HIV confirmatory results, and the patient died soon after admission.”
Wai CT, Tambyah PA. False-positive HIV-1 ELISA in patients with hepatitis B. Am J Med. 2002 Jun 15;112(9):737.
“Among those [tested for HIV at various US STD clinics] reporting a previous positive test result (n=740), 91% had positive test results in the serosurveys [which means that 9% either had false negative test results this time, had previously had a false positive or had ‘forgotten’ their previous death sentence]…among those reporting a previous indeterminate result (n=52), 21% had positive test results”
Weinstock H et al. Unrecognized HIV infection among patients attending sexually transmitted disease clinics. Am J Public Health. 2002 Feb;92(2):280-3.
“In a case that raises questions about the accuracy of HIV tests, an Oklahoma man has won a $1.4 million settlement nine years after a health clinic mistakenly told him he was infected with the virus that causes AIDS...In one of [Dr. Horberg’s] own cases a few years ago, he says, a woman insisted she could not have contracted HIV. She turned out to be right. She wasn't infected, despite a positive test result. "We did a mega work-up, kept following her every six months, and she was still negative," he says. "She never showed any sign of the virus, and her [immune system strength] was better than half the U.S. population."...Some people do worry that they got the wrong test results, Horberg says. Following the Oklahoma verdict, "I had tons of people calling and saying they wanted to be re-tested. You re-test them if that's what it takes to convince them that it's accurate," he says. [and they can be convinced without re-testing?]
Dotinga R. HIV court case raises questions on test. HealthScoutNews. 2002 Jan 23
“The Western blot assay, the most commonly used confirmatory test for human immunodeficiency virus (HIV) antibody detection, is expensive and may give indeterminate results. The Joint United Nations Programme on HIV/AIDS and World Health Organization therefore recommend three testing strategies for alternative HIV confirmation to maximize accuracy while minimizing cost. All three strategies (Strategy I, II, and III) have algorithms involving the use of one to three enzyme-linked immunosorbent assays (ELISA) and/or simple/rapid assays. Which strategy is most appropriate depends on the objective of the test, the prevalence of HIV in the population, and whether or not the patient is symptomatic (1). Strategy III involves the use of three immunoassays, each using different antigen preparations and/or different test principles. Sera are considered HIV antibody positive when all three tests are reactive. This most stringent of the alternative strategies is recommended for the diagnosis of HIV in asymptomatic persons in low-prevalence populations (10%). We report six cases tested during 1994 to 1997 where the use of Strategy III would have caused a false-positive result. These patients were asymptomatic and were tested for HIV antibodies for work permit applications (five) and antenatal screening (one)…From March 1994 to September 1997, 2,256 samples were submitted to our laboratory for the confirmation of HIV antibodies. The samples, referred by screening laboratories, had either reactive or grey zone HIV screening test results and were then subjected to Strategy III. Altogether, 61 samples had reactive results for all three immunoassays but had at least one low OD/CO result. Western blot testing confirmed 31 (50.8%) to be positive, 2 (3.3%) negative, and 28 (45.9%) indeterminate. Almost half of such samples could have been mislabeled as HIV positive according to the Strategy III criteria. The six samples described were selected because PCR results as well as serial serology were available.”
Ngan CC et al. Alternative strategies for confirmation of human immunodeficiency virus infection require judicious use. J Clin Microbiol. 2002 Jan;40(1):314-5.
“Between 1996 and 2000, a total of 12,124 samples were tested for HIV-1 antibodies. A total of 1,437 plasma specimens (11.9%) were HIV-1 antibody positive. Of these, 91 ( 0.8%) gave equivocal results, with discordant serological data and indeterminate WB profiles. The WB reactivities measured on 91 indeterminate test results are summarized in Table 1. Most of the indeterminate WB results were due to antibodies against the HIV-1 core antigen p24 (30.4%). In addition, reactivities to pol p51 (13.9%), pol p66 (14.6%), and env gp41 (15.2%) antigens were frequent. Isolated p17 reactivity was observed rarely (only 2.3% of the samples). A total of 12 samples (13.3%) displayed reactivity to two of the three proteins p24, gp41, and gp120/160 and thus can be considered positive by CDC criteria…Among 1,475 HIV-negative cohort participants, 31 (2.1%) had at least one indeterminate WB test result during follow-up, of which 19 (61%) were related to false-positive ELISA results only, 11 (36%) were related to false-positive HIVSPOT test results only, and 1 (3%) was related to both (Table 1). Most of the initially indeterminate WB assays (30 of 31 [97%]), including samples considered positive by the CDC criteria (6 of 6), were negative when retested. One subject with initial indeterminate WB profile was negative throughout 30 months of follow- up, at which time he seroconverted. Only two samples remained persistently indeterminate (as long as 18 and 48 months, respectively) without developing any WB reactivity that indicated seroprogression. In addition, 17 indeterminate WB assays, including the two samples that persistently gave indeterminate WB profiles, were assessed by NASBA for HIV-1 viremia. Plasma HIV-1 viremia was not detected in any of the above specimens…In multivariate analysis, false-positive HIVSPOT test results were independently associated with cigarette smoking and lower hemoglobin levels whereas false-positive ELISA results were independently associated with male gender and lower hemoglobin levels.”
Meles H et al. Indeterminate human immunodeficiency virus Western blot profiles in ethiopians with discordant screening-assay results. Clin Diagn Lab Immunol. 2002 Jan;9(1):160-3.
“An association was noted between the presence of red blood cells in CVL [Cervico-Vaginal Lavage] and HIV-1 shedding [i.e. detection of RNA believed to be diagnostic for HIV in the cervix/vagina]
Kovacs A et al. Determinants of HIV-1 shedding in the genital tract of women. Lancet. 2001 Nov 10;358(9293):1593-1601.
“During a prospective study of seronegative sexual partners of known HIV-1-infected patients [4], we identified two apparently transiently infected individuals (nos. 1 and 2) using a live-cell immunofluorescence assay (IFA) as a test for serum anti-HIV-1 antibodies, HIV-1 DNA amplification by PCR, and HIV-1 culture from the PBMC of the subjects (Table 1). These two were `early-infected' individuals previously reported (identified by their blood sample codes as R6 and R78) who possessed serum anti- HIV-1 antibodies that reacted with native HIV-1 antigens in live-cell IFA, but did not react in the standard Food and Drug Administration-approved denatured-antigen EIA or Western blot. These antibodies were later shown to react to conformational epitopes of HIV-1 Env (gp160) and Gag (p55) precursor proteins, and appear to be the first antibodies induced after HIV infection (submitted for publication) [this paper details how, for these two subjects, all evidence for the presence of HIV disappeared even after extensive re-testing]
Sahu GK et al. Transient or occult HIV-1 infection in high-risk adults. AIDS. 2001 Jun 15;15(9):1175-7.
“Data from studies conducted in Africa have shown an association between Trichomonas [a vaginal parasite] and HIV infection, suggesting a two- to threefold increase in HIV transmission[4,13,14]. A cross-sectional study conducted among 1,209 female sex workers in the Ivory Coast found an association between HIV and Trichomonas infection in bivariate analysis (crude odds ratio 1.8, 95% confidence intervals 1.3, 2.7). In another cross-sectional study performed in Tanzania among 359 women admitted to a hospital for gynecologic conditions, Trichomonas was more common in women with HIV infection in multivariate analysis (odds ratio 2.96, no confidence intervals provided, p<0.001). While such cross-sectional studies are limited by the issue of temporal ambiguity, i.e., lack of information on whether Trichomonas infection preceded HIV, these preliminary findings were subsequently reinforced in a single prospective study from Zaire[4]. This study, in which 431 HIV-negative female prostitutes were evaluated over time, found that prior Trichomonas infection was associated with a twofold increased rate of HIV seroconversion in muiltivariate analysis. [The authors did not consider the possibility that this infection could result in the production of antibodies that cause cross-reactions on HIV tests, and do not actually indicate an HIV infection]

Sorvillo F et al. Trichomonas vaginalis, HIV, and African-Americans. Emerg Infect Dis. 2001;7(6):927-32.
“HSV-2 [Herpes Simplex Virus-2] seropositivity was a strong independent risk factor for HIV infection with odds ratios of 5.3 for men and 8.4 for women [Another interpretation is that a high level of antibodies makes a (false) positive HIV test more likely]
Auvert B et al. HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behaviour. AIDS. 2001;15(7):885-98.
“100 adult patients (68 males; 32 females) with feverish illness were admitted to New Civil Hospital, Surat, India…peripheral blood smears showed malaria parasites in varying numbers. These patients did not have any risk factors for HIV infection. 25, age- and sex-matched healthy volunteers (17 males; 8 females) from the same community, geographical area and socioeconomic group were used as controls. None of the controls had any risk factors for HIV infection, and had had no febrile illness in the preceding six months…Two patients (6%) in the severe P. falciparum [malaria parasite infected] gropu tested positive for HIV-1 and -2 using ELISA…Western blotting proved persistently negative. No patient with low-level parasitaemia…tested positive…treating physicians should exercise extreme caution when interpreting such tests in a patient with PUO [fever of unknown origin] from an area where malaria is endemic, and in whom low level parasitaemia may have escaped detection.”
Ghosh K et al. False-positive serological tests in acute malaria. Br J Biomed Sci. 2001;58(1):20-3.
“From July 1, 1999, to November 30, 1999, 2,518 HIV Western blots were performed. Of these, 47 (1.9%) showed NSS [non-specific staining]…Of the 47 samples, 11 (23%) had a positive HIV-1 ELISA result, and results for 36 (77%) were negative. Presumably all of these patients had a positive HIV ELISA result in another laboratory, since samples were sent to our laboratory for confirmatory Western blot testing only. Each of the 11 samples with a positive HIV-1 ELISA result in our laboratory was only slightly above the positive cutoff for the assay. Most true-positive samples have signal/cutoff ratios greater than 5.0, while the ELISA-positive samples in our study had signal/cutoff ratios ranging from 1.02 to 2.98.”
Willman JH et al. Multiplex analysis of heterophil antibodies in patients with indeterminate HIV immunoassay results. Am J Clin Pathol. 2001 May;115(5):764-9.
“Kaushalya greets visitors with a warm welcome, hot tea and biscuits, but her big dark eyes look sad. In the last three years, the 29-year-old woman has lost her husband and social life. ''They broke our lives four years ago,'' she says softly while other members of the family nod. The local hospital said that Kaushalya's husband died of AIDS. Doctors at the medical college in Rohtak city later explained that Kaushalya and her daughter too had tested HIV-positive. The doctors pressured Kaushalya, who was in her sixth month of pregnancy, to get an abortion because of her HIV-infection. ''By telling me a lie they made me lose my only son,'' the young widow mourns. But late last year, a second test [probably a Western Blot or a second ELISA] showed that neither Kaushalya nor her daughter had the AIDS virus. Other members of the family too have since been tested negative for HIV. Like most Indian hospitals, the Rohtak hospital carried out only a single HIV test [ELISA] on her husband. In most other nations, at least three tests with similar results [two ELISA and one Western Blot] are required before a patient is confirmed HIV-positive. However, her family is still well known as 'the family of Chochi's first AIDS case. ''For years we lived with the trauma that the whole family was finished. But it all was a big fraud,'' says Kaushalya's father-in- law Mangaram Joon.”
Oberhuber N. India:Village Still to Recover from AIDS 'Stigma'. Terraviva Europe Daily Journal. 2001 Jan 15
“Between January 1, 1989 and July 31, 1995, voluntary preoperative screening tests for human immunodeficiency virus (HIV) infection, using an enzyme-linked immunosorbent assay, were completed on 2,727 patients who underwent elective orthopedic surgical procedures. There were 2,719 (99.7%) negative, 4 (0.15%) positive, and 3 (0.11%) false-positive results; 1 test was indeterminate (0.04%)”
LaPorte DM et al. Human immunodeficiency virus testing for elective orthopedic procedures: results in a community-based hospital. Orthopedics. 2001 Jan;24(1):52-5.
“During the next phase of testing (pools of 16 and inclusion of seroreactives), the initial reactive rate (through April 23, 2000) increased to 0.24% (646 reactive pools); the number of individual donations that were NAT reactive was 193 (0.07%). Of those, 178 have been NAT false-positive results (1:24,000) or a positive predictive value of 7.8%.”
Stramer SL. Nucleic acid testing for transfusion-transmissible agents. Curr Opin Hematol. 2000 Nov;7(6):387-91.
“We report the case of a sexually active woman with symptoms suggestive of ARS [Acute Retroviral Syndrome] who had a false-positive HIV-1 RNA assay result...Laboratory evaluation revealed negative results on HIV-1 ELISA and Western blot [antibody tests]. However, an HIV-1 RT-PCR [viral load] assay...revealed a viral load of 623 copies/ml, through p24, gp120, and gp160 antigens were not present. The HIV-1 RT-PCR assay was repeated and revealed a similar measurement...Subsequent studies 2 weeks later revealed an undetectable HIV-1 RNA viral load, as well as negative results on HIV-1 ELISA and Western blot serologies. Two months later, the patient’s symptoms [headaches, swollen glands etc.] had completely resolved...Four months after the onset of symptoms, the patient remained seronegative for HIV-1 infection”
More D et al. Utility of an HIV-1 RNA assay in the diagnosis of acute retroviral syndrome. S Med J. 2000 Oct;93(10):1004-6.
“As the number of women being screened has increased, the proportion of false-positive and ambiguous (indeterminate) test results has increased and the positive predictive value (PPV) of the standard HIV test has decreased”
Doran TI, Parra E. False-Positive and Indeterminate Human Immunodeficiency Virus Test Results in Pregnant Women. Arch Fam Med. 2000 Sep/Oct;9:924-9.
[conditions associated with false positive ELISA are] autoimmune disease, renal failure, cystic fibrosis, multiple pregnancies, blood transfusions, liver diseases, parenteral substance abuse, hemodialysis, or vaccinations for hepatitis B, rabies, or influenza…Causes of indeterminate WB [Western Blot] results include…nonspecific antibody reactions (eg, due to lymphoma, multiple sclerosis, injection drug use, liver disease, or autoimmune disorders). Also, there appear to be healthy individuals with antibodies that cross-react with specific HIV-1 peptides or recombinant antigens…The Association of Public Health Laboratories now recommends that patients who have minimal positive results on WB, eg, p24 and gp160 only, or gp41 and gp160 only, be told that these patterns have been seen in persons who are not infected with HIV and that follow-up testing is required to determine actual infective status. The clinician must judge the test results within the context of other epidemiological and clinical information [i.e. gay men and IV drug users are likely to be defined as positive based on this prejudice in the presence of ambiguous test results]. In the appropriate clinical setting, positive ELISA and WB test results in patients with a normal CD4 + count and CD4/ CD8 ratio and undetectable HIV-1 RNA should be questioned, repeated, or confirmed with supplemented testing. A false-positive serological test result may be supported by normal CD4 + count and CD4/CD8 ratio and undetectable HIV-1 RNA, but is ultimately established by subsequent serological testing and, especially, close follow-up. [i.e. there is no test that can be absolutely relied on]
Mylonakis E et al. Report of a False-Positive HIV Test Result and the Potential Use of Additional Tests in Establishing HIV Serostatus. Arch Intern Med. 2000 Aug 14/28;160(15):2386-8.
“In 1984, I was informed that test results showed that I had an ‘HIV’ infection and I had at best five years to live...I am now 50 years old and have taken back control of my own health. For the past eight years, I’ve had no need for doctors, and have been on a diet of pure water, organic food and a positive belief system.”
Anderson A. Letter. Alive. 2000
“False reactivity with at least 1 of the 6 [rapid] HIV screening tests was found in sera from 21 of the 66 patients with malaria and from 4 of 9 patients with dengue. Specificity of individual kits ranged from 77% to 100%. Malaria antibody titers [levels] did not correlate with false-reactive HIV-1 results from test A, the least specific kit. 6 of the 12 malaria sera tested positive by IFA [immuno-fluorescence assay]. Test A was reactive in 4 of the 6 sera…and was negative by use of IFA in 5 of 14 sera. All dengue sera were negative on the basis of malaria IFA, but half were reactive by test A…false reactivity may occur with [HIV-1 rapid tests] and…it is important to define the cross-reactivity associated with endemic diseases, because resource-poor regions of the world rely more and more on these rapid, simple HIV tests.”
Watt G et al. Human immunodeficiency virus type 1 test results in patients with malaria and dengue infections. Clin Infect Dis. 2000 May;30(5):819.
“Negative results (<50 copies/mL), were obtained in 30/32 (94%) [bDNA 3.0] assays [meaning that false-positive results were obtained in 2/32 or 6% of cases]
Erice A et al. Performance characteristics of the bDNA 3.0 assy for quantitation of HIV-1 RNA in plasma [abstract]. 7th Conf. Retroviruses and Opp Infections. 2000 Jan 30-Feb 2
“In Japan, HIV prevalence is very low and the majority of the HIV screening test-positive (reactive) cases turned out to be false positive.”
Imai M et al. [Kinetic analysis of anti-HIV titer in early stage of HIV infection--a new testing strategy to differentiate early HIV infection individuals from false positive cases]. Kansenshogaku Zasshi. 1999 Dec;73(12):1183-6.
“Rich and colleagues demonstrated difficulties with the use of HIV-1 plasma viral load testing to diagnose HIV infection. We, too, have witnessed false-positive results on testing for HIV-1 with polymerase chain reaction (PCR) in a man presenting with encephalopathy secondary to alcohol withdrawal and hypertension. A 59-year-old man known to have type 2 diabetes mellitus, alcoholism, hypertension, and chronic obstructive lung disease was hospitalized for headache and confusion. He had no history of trauma, intravenous drug use, sexual promiscuity, homosexual encounters, transfusion, or sexually transmitted disease. Physical examination confirmed disorientation without localizing signs. Magnetic resonance imaging showed increased cerebral atrophy, consistent with the patient’s age. Lumbar puncture was normal. Nitroprusside was used to control hypertension. The result on enzyme-linked immunosorbent assay for serum HIV was negative, whereas the result on testing for serum HIV-1 RNA by using reverse-transcriptase PCR was positive. Results of repeated enzyme-linked immunosorbent assay of serum and cerebral spinal fluid and PCR assays for HIV RNA were all negative. The HIV-1 PCR assay was designed to monitor HIV therapy, not to diagnose HIV infection. For diagnostic tests, prior probability of a positive test result needs to be considered. In patients (like ours) with a low prior probability of disease, almost all positive test results are false positive. Our urge to confirm the cause of acute encephalopathy rather than accept a diagnosis of exclusion resulted in inappropriate use of HIV-1 PCR. This case confirms the importance of prior probability in diagnostic assays. We concur with Rich and colleagues that lowlevel positive results on HIV-1 PCR must be interpreted cautiously within the context of the patient’s entire picture.”
Havlichek DH, Hage-Korban E. False-positive HIV diagnosis by HIV-1 plasma viral load testing. Ann Intern Med. 1999 Nov 16;131(10):794.
“We describe here a case of heterophile antibodies that are cross-reactive with bovine and caprine proteins occurring in a 22-month-old child, causing false-positive immunoassay results to human immunodeficiency virus type 1 (HIV-1) and a number of other infectious serology tests...we believe the positive test results observed in this patient were due to heterophile antibodies reactive with BSA and caprine proteins. All of the positive tests observed used BSA [bovine serum albumin] as a blocking agent for the preparation of the microELISA reaction wells.”
Willman JH et al. Heterophile Antibodies to Bovine and Caprine Proteins Causing False-Positive Human Immunodeficiency Virus Type 1 and Other Enzyme-Linked Immunosorbent Assay Results. Clin Diagn Lab Immunol. 1999 Jul;6(4):615-6.
“Abbott Laboratories state that their ELISA test is 100% sensitive and 99.9% specific and this would seem excellent, more reliable, in fact, than many other tests used elsewhere in medical practice…[However,] If…the incidence of HIV infection in the population was 0.1%, in a population of 1,000 there would be one true positive and one false positive, and the test would be considered very unreliable.”
Harrison R, Corbett K. Screening of pregnant women for HIV: the case against. The Practising Midwife. 1999 Jul/Aug;2(7):24-9.
“The Centers for Disease Control and Prevention (CDC) states that the two tests used to identify HIV - the ELISA and the Western blot (WB) - used in combination, have a better than 99% accuracy rate, but only if they are performed repeatedly. (The exact rate is unknown and the CDC states that it has no data on just how many false positives versus false negatives occur!)…The CDC estimates that 0.6% of Americans are HIV-positive…Using the CDC estimate that 0.6% of Americans are HIV-positive, in a population of 10,000, 60 Americans would test positive! This 60 must include all the false positives, 30, leaving only 30 people actually infected. This leads to the following conclusion: using a 99% accuracy, one finds as many false positives as true positives. Even if the results of both AIDS tests, the ELISA and WB, are positive, the chances are only 50-50 that the individual is infected.”
Stine GJ. Testing for Human Immunodeficiency. AIDS Update. 1999;357-371.
“We cared for a woman initially seen because of Rhe[s]us isoimmunization who consented to routine HIV screening at 20 weeks’ gestation. The initial EIA result was reactive, as was the result of a repeat test 2 weeks later, at which time a supplemental EIA test (nonreactive) and Western blot analysis (indeterminate) were requested. One week later, the result of a third screening EIA test was nonreactive. A month later, another screening EIA test gave a reactive result, a supplemental EIA test result was nonreactive, and a Western blot analysis result was indeterminate for all 3 determinants of HIV-1; the patient’s HIV viral load was < 500 copies/mL. At 34 weeks’ gestation (when all results were finally to hand) the patient was reassured that she was HIV negative. Twelve weeks had passed since the first positive test result. Understandably, the patient was under considerable stress during this time…We had been unaware that multiparity, multiple previous transfusions and auto-immume disorders are all risk factors for false-positive reactions (in non-pregnant populations) because of anti-HLA-DR or other antibodies. Pregnant women are often multiparous, may have a prior history of ante- or post-partum hemorrhage requiring transfusion, and belong to the gender and age groups in which auto-autoimmune phenomena are most common”
Magee LA et al. False-positive results in antenatal HIV screening. CMAJ. 1999 May 4;160(9):1285.
“18 subjects had 1 or 2 positive results with v.2.0 and an undetectable confirmatory test for a false positive rate of 4.4%. The rate is similar at baseline (9/183 subjects = 4.9%), wk. 4 (7/162= 4.3%) and wk. 26 (2/44 = 4.5%). Of the 18 pos. specimens, 9 tested pos. once and 9 twice. With version 3.0, 11 of 67 samples tested were pos. (16.4%). 6 were pos. once and 5 twice. The range of false pos. rates was 9.1% at wk. 4 (total of 22 specimens) to 26.7% at wk. 26 (total of 15 specimens). A week 4 sample with two values of 8,000 copies/ml on v.2.0 was neg. by DNA PCR, p24 antigen and Western Blot. Follow-up testing of this subject at wk. 26 was negative for HIV antibody and RNA. The emotional impact of a false positive screening RNA test in a recently exposed person is significant. With the high false positive rate, we do not advocate the routine use of HIV RNA tests to screen asymptomatic people. The high rate of repeat false positive tests in a given sample (50%) suggests a possible biologic mechanism”
Roland ME et al. Pitfalls of HIV RNA testing in the San Francisco post-exposure prevention (PEP) project. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6(101):Abstract no. 179.
“Plasma viral load tests for HIV-1 were neither developed nor evaluated for the diagnosis of HIV-1 infection; therefore their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. We report two cases of false-positive results obtained by using branched-chain DNA assay…and one case…by using HIV reverse transcriptase polymerase chain reaction (RT-PCR)…These three cases illustrate the potential problems of using HIV-1 plasma viral load tests for diagnosis of HIV infection…Only patients who have a high pre-test probability of a positive result should be evaluated for primary infection by using plasma viral load testing [i.e. preconceptions about risk groups such as gay men makes a positive test more likely]…Their performance in patients who are not infected with HIV is unknown”
Rich JD et al. Misdiagnosis of HIV Infection by HIV-1 Plasma Viral Load Testing: A Case Series. Ann Intern Med. 1999 Jan 5;130(1):37-9.
“Of 421 donors who were positive for HIV-1 by Western blot, 39 (9.3%) met the criteria of possible false positivity because they lacked reactivity to p31. Of these, 20 (51.3%) were proven by PCR not to be infected with HIV-1. The false-positive prevalence was 4.8% of Western blot-positive donors and 0.0004% (1 in 251,000) of all donors (95% confidence interval, 1 in 173,000 to 1 in 379,000)…A review of the 5.02 million donations in the 1991-1995 REDS donation database revealed that 4,650 were anti-HIV EIA repeat-reactive and 421 were HIV-1 Western blot positive (0.008% of all donations, 9.0% of EIA repeat-reactives) using the 1993 FDA interpretive criteria. 39 (9.3%) of the Western blots with positive results lacked the p31 band.”
Kleinman S et al. False-positive HIV-1 test results in a low-risk screening setting of voluntary blood donation. JAMA. 1998 Sep 23/30;280(12):1080-5.
“RAK antigens p120, p42, and p25 exhibit molecular and immunological similarity to the proteins encoded by human immunodeficiency virus type 1 (HIV-1) and are expressed by 95% of breast and gynecological cancer cases in women and prostate cancer cases in men.”
Rakowicz-Szulczynska EM et al. Human immunodeficiency virus type 1-like DNA sequences and immunoreactive viral particles with unique association with breast cancer. Clin Diagn Lab Immunol. 1998 Sep;5(5):645-53.
“A small number (15% to 20%) [!] of [ELISA and WB antibody] tests from low-risk patients will be indeterminate and remain so even if repeated over many months”
Minkoff HL. Human Immunodeficiency Virus in pregnancy. Semin Perinatol. 1998 Aug;22(4):293-308.
“A 5-month-old boy [of injection drug-using parents] was diagnosed with severe thrombopenia…The child’s plasma viral load was 3044 HIV RNA copies/ml, and he began to receive zidovudine plus didanosine…Unexpectedly, days later it was discovered that HIV antibodies [ELISA and WB] were not detected in sera collected from the child or from his parents. The plasma viral load was examined in a new specimen using the same technique (HIV Quantiplex, Chiron, Madrid, Spain) and again it gave a positive result of 5120 HIV RNA copies/ml.”
de Mendoza C, Holquin A, Soriano V. False positives for HIV using commercial viral load quantification assays. AIDS. 1998;12(15):2076-7.
“A 24-year-old medical student was evaluated for a 2-week history of fever, night sweats, fatigue, and headaches. He denied gastrointestinal symptoms, rash, sore throat, jaundice, or arthralgias. In addition, he denied injection drug use, sexual promiscuity, blood transfusion. He reported a needle-stick injury that occurred while he was repairing a laceration secondary to a vaginal delivery, 4 weeks before the onset of his symptoms. At the time of the injury, he tested seronegative for HIV and hepatitis B…[at the time of first evaluation] The HIV EIA was repeatedly positive, but the HIV western blot and p24 antigen assay were negative…High levels of IgM antibody to CMV were detected…Two weeks later, the patient’s symptoms had resolved completely. However, the HIV EIA remained positive, the IgM titer had increased to 4.440, and the HIV western blot remained negative. The patient did well during the next 17 months; hepatic enzyme levels returned to normal and the HIV EIA was nonreactive.”
Bronze MS et al. False-positive enzyme immunoassay for Human Immunodeficiency Virus due to acute Cytomegalovirus infection. Clin Infect Dis. 1998;27:221-2.
“No patient with liver disease showed reactivity to the HIV-1 gag and envelope proteins…Immunoblot reactivity was generally restricted to p24 and, in a few cases, p17 in the patients with liver disease. The frequency of HIV-1 p24 gag reactivity in the patients with primary biliary cirrhosis was not significantly different from that in the groups with systemic lupus erythematosus, chronic viral hepatitis, or other biliary disorders, but it was significantly higher than the frequencies among the healthy volunteers and patients with alcohol-related liver disease or alpha1-antitrypsin deficiency”
Mason A, Xu L, Guo L et al. Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders. Lancet. 1998 May 30;351(9116):1620-4.
“Specimens were studied from a mother and her child, both with suspected transient viremia. The mother had 2 and the infant 3 positive HIV-1 cultures, but subsequently both individuals became negative for HIV-1 by nPCR, standard virus cultures, CD8+-depleted virus cultures, and enzyme-linked immunosorbent assay. HIV-1 RNA and DNA were not detected in two lymph nodes taken from the mother 3 and 4 years after the last virus-positive culture. PCR amplification and DNA sequence of HIV-1 env sequences from the...culture supernatants were performed in separate laboratories to eliminate the possibility of cross-contamination. Phylogenetic analysis found that none of the five isolates were genetically linked. Although it is improbable, these 5 virus isolates appear to have arisen from 5 separate incidents of specimen contamination or mislabeling. This case remains enigmatic, however, in that both the mother and infant had strong CD8+ cytotoxic lymphocyte proliferation to multiple HIV-1 antigens.”
Frenkel LM et al. Genetic evaluation of suspected cases of transient HIV-1 infection of infants. Science. 1998 May 15;280(5366):1073-7.
“To provide a comparison with previous surveys, panels of patient sera were first reacted with commercially available Western blot strips for HIV-1. Blot data were scored as negative, plus-minus, and 11 to 41 on a visual basis by two independent observers. Those which were plus-minus or negative were considered to be negative…Nearly all significant reactivities were restricted to p24. Of the 38 control sera, 6 (16%) were positive (1+); of the 39 SS [Sjögren’s syndrome] sera, 10 (27%) were positive; and of the 20 SLE [systemic lupus erthematosus] sera, 11 (55%) were positive. The strongest reactions were most common in the SLE samples…[in ELISA testing] sera from SS patients demonstrated a reactivity significantly different from that of controls. Compared with controls, these sera had significantly increased reactivity to peptides F and H and significantly diminished reactivity to peptides A and P. Sera from SLE patients exhibited significantly increased reactivity to peptides E, H, and P compared with that of controls…In conclusion, we have found that a large percentage of 59 SS and SLE sera react significantly and specifically with only a few peptides derived from the sequence of HIV p24 [this means that with the small sample they have a false positive on the entire testing sequence is unlikely, but much increased over the general population]
Deas JE et al. Reactivity of sera from systemic lupus erythematosus and Sjögren's syndrome patients with peptides derived from human immunodeficiency virus p24 capsid antigen. Clin Diagn Lab Immunol. 1998 Mar;5(2):181-5.
“Initial testing of plasma by RNA RT-PCR was reported as positive. This result was not confirmed by viral cultures, nested DNA PCR, western blot, or EIA. Additional RNA RT-PCR assays gave positive results from earlier occasions in the vaccine trial. Eventually, testing of all previously reactive samples by RNA RT-PCR was repeated in a quality-controlled laboratory, and confirmed the negative HIV-1 status of the individual. Interpretation This case report exemplifies the difficulties with use of viral-genome measurement as a screening test to diagnose HIV- 1 infection, particularly in individuals who have ever participated in HIV-1 vaccine trials. Monitoring of large numbers of phase III vaccinees by RNA RT-PCR will not be feasible. The design of efficacy trials for new vaccines should be in parallel with development of antibody-based diagnostic tests that are capable of differentiating between immunisation and true HIV-1 infection.”
Schwartz DH et al. Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of false-positive PCR. Lancet. 1997 Jul 26;350(9073):256-9.
“All blood collections from January 1994 to March 1996 were screened for anti-HIV by HIV-1/2 enzyme immunoassay (EM). Repeatably reactive results were confirmed by HIV- 1 WB. AIl WB-positive donors were interviewed regarding risk behavior and offered repeat HIV testing. HIV polymerase chain reaction (PCR) was added to repeat HIV testing for more recent donors. Results were considered false-positive when the donor denied risk factors and 1) repeat samples tested EM-negative or 2) repeat samples tested PCR-negative and either WB-negative or WB-positive only by the new criteria (formerly, WB-indeterminate). Four donors (2 men and 2 women, aged 27-47 years) were identified as having had a false-positive HIV WB interpretation for their index donations. Two donors had p24 antigen and env WB bands and two donors had env bands only. Two donors tested negative by EM and PCR, 13 and 19 months after donation. One donor was persistently WB positive (new criteria only), but was PCR negative 5 weeks after donation. Tho samples taken from one donor 1 month after donation were negative in EM. These donors represent 11 percent of all WB-positive donors during the study period. This experience is consistent with a recent estimate, based on a 4-year database from 5 blood centers in the United States, that 4.5 percent of WB results in blood donors are false positive [and Western Blot is the ‘confirmatory’ test that is rarely questioned]
Cable RG et al. Interpretation of false-positive human immunodeficiency virus type 1 western blot assays in blood donors. Transfusion. 1997 Jun;37(6):670.
“As HIV antibody assays have become more sensitive over the years, the probability of a false-positive reaction in 2 assays based on a different principle is not negligible [i.e. as HIV antibody tests have produced more reactive results the risk of a false positive even with 2 different tests is not negligible]
Joint United Nations Programme on HIV/AIDS (UNAIDS)-WHO. Revised recommendations for the selection and use of HIV antibody tests. Wkly Epidemiol Rec. 1997 Mar 21;72(12):81-7.
“71 (42%) [of a group of Zambians] reported themselves positive for HIV infection. 21 (30%) of those self-reporting as HIV-positive were shown to be sero-negative. 51 self-reported as HIV-negative, and 19 (37%) of these were sero-positive [this could be because they had had previous HIV tests with discordant results or because they thought they were HIV positive (or not) due to their general health or because they were lying, for unknown reasons]
Chintu C et al. False-positive self-reports of HIV infection. Lancet. 1997 Mar 1;349(9052):650.
“the EIA [this test] was designed to be extremely sensitive. As a result, non-specific reactions may be seen in samples from some people who, for example, due to prior pregnancy, blood transfusion, or other exposure, have antibodies to the human cells or media in which the HIV-1 is grown for manufacturer of the EIA. The risk of an asymptomatic person with a repeatably reactive serum sample developing AIDS or an AIDS-related condition is not known.”
Human Immunodeficiency Virus Type 1 HIVAB HIV-1 EIA. Abbott Laboratories. 1997 Jan
“For 859 specimens from uninfected infants [based on two negative cultures], 97% had PCR negativity, 2% had PCR positivity and 1% had indeterminate status”
Bremer JM et al. Diagnosis of infection with human immunodeficiency virus type 1 by a DNA polymerase chain reaction assay among infants enrolled in the women and infant's transmission study. J Pediatr. 1996 Aug;129(2):198-207.
“Not all persons infected with HIV-1 will test positive; not all persons testing positive are infected with HIV-1…inaccurate results may occur and a positive test result alone does not mean I have AIDS or will ever develop AIDS…an indeterminate result means the result is neither negative nor positive”
Home access HIV-1 test system. Home Access Health Corp.. 1996 May
“False positive results may occur due to non-specific binding to assay materials and not from infection with HIV-1.”
Antibody to Human Immunodeficiency Virus type 1 (human); HIV-1 p24 antigen neutralization kit. Coulter. 1996 Apr
“False positive results [with this HIV-1 antigen test kit] may occur due to non-specific binding to assay materials, and not from infection with HIV-1”
Antibody to Human Immunodeficiency Virus type 1 p24 antigen (murine monoclonal). Coulter. 1996 Apr
“Our previous data demonstrated that anti-gp41 MAb [monoclonal antibody] 781.4, as well as human serum antibodies against the same gp41 epitope, bound specifically to the surface of [HIV-uninfected] human astrocytoma cells…Antigens from U-138 MG human astrocytoma cells that cross-react with anti-gp41 MAb 781.4 were isolated by immunoaffinity chromatography. Two major bands of approximately 100 and 200 kDa in molecular mass were visible…Western blot analyses of the purified preparations demonstrated that both the 100- and 200-kDa proteins were immunoreactive with MAb 781.4 as expected, although the reactivity of the 100-kDa protein was much greater…When the N-terminal sequences obtained from peptides [generated by partial digestion of the 100-kDa protein] A, B and C were subjected to analyses…the amino acid sequence of each of the three peptides was found to be homologous to a human non-muscle isoform of alpha-actinin…we analyzed their immunoreactivity with the anti-gp41 MAb 781.4 and an anti-alpha-actinin specific MAb by Western blot. The two antibodies displayed the same reactivity…In addition we used an ELISA with the purified chicken alpha-actinin protein…The anti-gp41 as 598-609 MAb 781.4, as well as another antibody, designated MAb 781.3, which recognizes an epitope within gp41 aa 581-597 were immunoreactive with alpha-actinin”
Spehar T, Strand M. Molecular mimicry between HIV-1 gp41 and an astrocyte isoform of alpha-actinin. J Neurovirol. 1995 Dec;1(5-6):381-90.
“The causes of false-positives [on ELISA antibody tests] are listed in Table 1 [Hematologic malignant disorders, DNA viral infections, Autoimmune disorders, Multiple myeloma, Primary biliary cirrhosis, Alcoholic hepatitis, Influenza vaccination, Hepatitis B vaccination, Passively transferred antibodies, Antibodies to class II leukocytes, Renal transplantation, Chronic renal failure, Stevens-Johnson syndrome, Positive rapid plasma reagent test]
Cordes R, Ryan M. Pitfalls in HIV testing. Postgraduate Medicine. 1995 Nov;98(5):177-80, 185-6, 189.
“TABLE 1. Causes of FPRs by EIA Cause of FPRs (reference[s]): Performance and technical errors (104); Mislabeling of samples or wells; Carryover or cross contamination (76); Variability in test kits (60); Heat treatment of samples (24, 59); Purity of HIV-1 antigens; Presence of anti-HIV-1 antibodies in: Noninfected babies born to infected mothers; Recipients of unscreened immunoglobulins (45, 48, 68, 109); Recipients of HIV-1 trial vaccines; Presence of antibodies reactive with: Human leukocyte antigens or other cellular components, such as those observed in Multiparous women and polytransfused patients (10, 55, 67, 87, 101); Patients on chronic hemodialysis (92, 111); Patients with autoimmune diseases (4, 16, 87, 108); Anti-idiotype antibody (conjugate) (26, 91); Recipients of influenza virus and hepatitis B virus vaccines (26, 71, 75); Patients infected with herpes simplex virus 2 (26); Epitope shared by HIV-1 and other retroviruses, rabies virus (91), or Mycobacterium leprea (61); Others Congenital bleeding disorders (107); Alcoholic hepatitis (82); Hematologic malignancies (108); Positive reagin test (42)

TABLE 3. Conditions associated with WBi [Western Blot Indeterminate] result: Incomplete generation or loss of antibodies; Early seroconversion (33, 73, 106); Late-stage disease (8); Massive proteinuria (85); Passive transfer of antibodies from: Infected mothers to noninfected children (18); Unscreened immunoglobulin preparations (48, 68, 109); Cross-reactivity with: Normal cellular constituents: nucleoproteins (99); and HLA (35); Other retroviruses: human T-cell leukemia virus type 1 and HIV-2 (33); Bacteria (Mycobacterium leprae [61]); Interfering factors or sample preparation In vitro hemolysis, elevated bilirubin, rheumatoid factor (17); Heat inactivation (24, 47); Antibodies generated by influenza virus vaccine (75); African sera (34a); Disease states Polyclonal gammopathies (17); Systemic lupus erythematosus (4)”

Nuwayhid NF. Laboratory tests for detection of human immunodeficiency virus type 1 infection. Clin Diagn Lab Immunol. 1995 Nov;2(6):637-45.
“Considerable variation was observed in the number of repeatedly false-positive reactions observed for each assay. Only one assay (ELISA 1) was 100% specific. The highest rate of false-positive results was obtained with tests 2 (10 [false positive results]) and 4 (8 [false positive results])…the highest rate of false-positive results was obtained by testing serum samples from high-risk individuals, patients with autoimmune diseases or acute viral illness, organ transplant recipients and pregnant women. In contrast, sera which were repeatedly reactive by ELISAs, but negative in Western blot, did not affect the specificity of the 6 assays”
Weber B et al. Evaluation of the reliability of 6 current anti-HIV-1/HIV-2 enzyme immunoassays. J Virol Methods. 1995;55(1):97-104.
“A case was defined as a donor whose blood donation tested reactive in screening tests [usually ELISA] for antibodies to at least two of…HIV-1, HTLV-1, and hepatitis C and had negative or indeterminate results in confirmatory or supplemental tests…70.3% of the cases compared with 22.6% of [matched] controls reported a recent influenza vaccination. A history of recent acute illness was [also] more common…A history of allergies and a history of recent vaccination other than for influenza were also more common among the cases than among the controls.”
Simonsen L et al. Multiple false reactions in viral antibody screening assays after influenza vaccination. Am J Epidemiol. 1995 Jun 1;141(11):1089-96.
“Reactivity of anti-HIV-l antibodies was examined in placental decidua of normal non-infected samples from second- and third-trimester. In all cases, cross-reactivity was observed in trophoblast cell populations within the decidua basalis and regions of the trophoblastic shell. Villous trophoblast also reacted in a manner consistent with our earlier reports. Specifically, villous cytotrophoblast expresses proteins which react with antibodies against HIV-l pl7/18 and gp120/160 epitopes while syncytiotrophoblast displays a limited expression pattern that suggests gp 120/ 160 cross-reactive epitopes are more restricted in distribution than p17/18 cross-reactive epitopes. Observations reported here extend our previous studies to the decidua and confirm that expression of HIV-l cross-reactive proteins is a general feature of trophoblast that appears to be related to the cellular differentiation state. In the case of anti-HIV-l p17/18 antibodies, reactivity was observed in both mononuclear extravillous trophoblast populations and placental bed trophoblastic giant cells…The overall point made by these data is that normal invasive placental trophoblast expresses proteins which have immunologic cross-reactivity with exogenous retrovirus (HIV-l) structural proteins.”
Lyden TW et al. Expression of endogenous HIV-1 crossreactive antigens within normal human extravillous trophoblast cells. J Reprod Immunol. 1995 Mar;28(3):233-45.
“HIV could not be isolated from the plasma of subjects with long-term nonprogressive HIV infection, but it could be isolated from lymph-node mononuclear cells (in seven patients) after coculture with phytohemagglutinin- activated mononuclear cells from an HIV-negative donor (data not shown).”
Pantaleo G et al. Studies in subjects with long-term nonprogressive Human Immunodeficiency Virus Infection. N Engl J Med. 1995 Jan 26;332(4):209-16.
“Enzyme linked immunosorbent assay-In the HTLV-I [a virus believed by Robert Gallo to be related to HIV] ELISA, four of 30 RA [rheumatoid arthritis] sera were considered positive…Sera were [also] tested against recombinant HIV-1 p24. However, in this assay system only one [of 30] RA serum and one pSS [primary Sjögren’s syndrome] serum [of 14], and two [of 80] control group sera (derived from two white osteoarthritis patients) were positive…Of the four sera considered positive for HIV-1 by ELISA…one demonstrated reactivity for p24 by HIV-1 Western blot. [these are still high false positive numbers]
Nelson PN et al. Polymerase chain reaction fails to incriminate exogenous retroviruses HTLV-I and HIV-1 in rheumatological diseases although a minority of sera cross react with retroviral antigens. Ann Rheum Dis. 1994 Nov;53(11):749-54.
“We report a false-positive result on an enzyme immunoassay screening test for antibodies to human immunodeficiency virus in a 32-year-old nonpregnant woman who belonged to none of the usual risk groups. Because of the patient's employment in an animal care facility, she had received a series of three vaccinations for rabies, and 16 days after the last vaccination, she had donated a unit of blood. It was during routine screening on a sample drawn at the time of donation that the repeatedly reactive enzyme immunoassay screening test occurred. The results of a Western blot were indeterminant. A polymerase chain reaction assay was negative for proviral DNA.”
Pearlman ES, Ballas SK. False-positive human immunodeficiency virus screening test related to rabies vaccination. Arch Pathol Lab Med. 1994 Aug;118(8):805-6.
“The results of this work indicate that certain anti-HIV antibodies cross-react with endogenous placental proteins. Anti-gp120/160 was generally reactive with villus cytotrophoblast cells from second trimester placenta and with limited regions of syncytium in third trimester placental tissue samples. Reactivity was mostly cytoplasmic, although some extravillus trophoblast cells stained in a manner suggesting surface membrane-related expression. This was also the case with anti-p17 staining of extravillus trophoblast. In villus placental tissue sections from the second and third trimester, anti-p17 reactivity was strongly associated with the cytotrophoblast layer. Limited syncytial areas also displayed an apical band of reactivity. These data demonstrate that HIV-1 cross-reactive protein epitopes are expressed within trophoblast of normal human placentae. In additional studies, it was observed that placental ERV particle isolates are cross-reactive with these antibodies and that these antibodies also cross-react with human choriocarcinoma cell lines BeWo, JAr, and JEG-3 that are not infected with HIV-1 (data not shown). These data suggest that human placental endogenous retroviral proteins may have antigenic similarity with exogenous HIV-1 and that expression of these proteins is a normal feature of trophoblast differentiation.”
Lyden TW et al. Anti-HIV monoclonal antibodies cross-react with normal human trophoblast. Placenta. 1994;15(Suppl 1):19-32.
“WB was considered diagnostic for HIV-1 if there was reactivity with two of three envelope bands (gp160/120 and gp 41). The rate of HIV-1 false-positive ELISAs was…63.6%…among uninfected leprosy patients…Of the cohort of 500 pregnant women, HIV-positive results were obtained by Abbott ELISA in…5.6%, Organon ELISA in…5.4%, and on both tests for…5.2%…WB were indeterminate in…83.6%…of 55 leprosy patients and...3.9%...of HIV-negative pregnant women.”
Kashala O et al. Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan. J Infect Dis. 1994 Feb;169:296-304.
“During a ten-month period 3 of 77 low-risk normal controls had positive ELISA tests. This gives a false-positive rate [on ELISA] of about 4% [manufacturer quotes 0.58%]…Case 1…a 38-year-old woman who had had unprotected anal intercourse twice in her life tested strongly positive for the presence of HIV antibodies. Further questioning revealed that she had had an outbreak of herpes simplex type 2 infection three weeks before…Case 2…a 23-year-old man with no known risk factors…he had been inoculated with the influenza vaccine two months before testing…Case 3…a 32-year-old man had no known HIV risk factors, but he had received the influenza vaccine two months before HIV testing. He also had had hepatitis C infection several years previously…we have screened another 50 subjects and have had two more false-positive ELISA results”
Challakeree K, Rapaport MH. False positive HIV-1 ELISA results in low risk subjects. Western Journal of Medicine. 1993 Aug;159(2):214-5.
“False-positive HIV ELISAs have been observed with serum from patients with a variety of medical conditions unrelated to HIV infection [but claims that these can be eliminated by use of Western Blot test or synthetic peptides in the test kits]…False-positive HIV ELISAs [also] occur because of human or technical errors associated with doing the tests or because of antibodies that coincidentally cross-react with HIV or nonviral components in the tests…Notable causes of false-positive reactions have been anti-HLA-DR antibodies that sometimes occur in multiparous women and in multiply transfused patients. Likewise, antibodies to proteins of other viruses have been reported to cross-react with HIV determinants. False-positive HIV ELISAs also have been observed recently in persons who received vaccines for influenza and hepatitis B virus [but again claims that these can be eliminated by Western Blot tests or use of synthetic peptides in tests]
Proffitt MR, Yen-Lieberman B. Laboratory diagnosis of human immunodeficiency virus infection. Inf Dis Clin North Am. 1993 Jun;7(2):203-19.
“When the EIA [enzyme immunoassay antibody test] is used to screen populations in which the prevalence of HIV-1 infection is low (e.g., blood donors), nonspecific reactions may be more common…Reactivity at only slightly above the cut-off value is more frequently nonspecific”
Human immunodeficiency virus type 1 HIVAB HIV-1 EIA. Abbott Laboratories. 1993
“The Western blot (WB) is the most commonly used test to confirm the presence of antibodies against the human immunodeficiency virus type 1 (HIV-1). Different criteria of interpretation of the band profile have been proposed with there being no unanimity as to its reliability…The presence of antibodies against HIV-1 was prospectively studied in 8,073 samples of subjects with risk of infection. A total of 1,993 (25%) were reactive by ELISA and 1,261 were analyzed by WB, with a semiquantitative reading of the bands with a point scale from 0 to 2 being performed. The final interpretation of the WB (negative, doubtful, or positive) was carried out following 5 recommendations of usage…In order of frequency, the most frequent bands in HIV-1 + individuals were gp160 (99%), gp120, p24, p31, p55, p68, gp41, and p17 (68%). In non infected individuals, the recognized bands were, in decreasing order, p24, p17, p55, p68, p31, and glucoproteins. Different criteria of interpretation of the Western blot provide different degrees of sensitivity and specificity. The Western blot is a non standardized, expensive, laborious technique of subjective interpretation which provides an appreciable number of undetermined results.”
Soriano V et al. [Evaluation of various criteria for the interpretation of western blot for the diagnosis of human immunodeficiency virus infection. Spanish Group for the Study of HIV-2]. Med Clin (Barc). 1993 Apr 17;100(15):561-6.
“From October 31 through December 15, 1991, 10 blood donors to the American Red Cross Blood Services, Badger Region (ARCBS) , were found to have false-positive screening enzyme-linked immunosorbent assays (ELISAs) for antibodies to two or more of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type 1 (HTLV-I), and hepatitis C virus (HCV)”
False-positive serologic tests for human T-cell lymphotropic virus type I among blood donors following influenza vaccination, 1992. MMWR. 1993 Mar 12;42(9):173-5.
“The specificity of immunoassays for detecting HIV antibodies has major shortcomings. Almost all reactions, especially in low risk populations, represent false-positive results. This has been observed with Western blot (WB), which is widely used as a confirmatory test…A serum panel of 21 blood-bank donors and two serum samples from patients with primary Sjögrem's syndrome were analysed…All sera were positive on two commercial WB assays, as well as on home-made blots using recombinant p24 proteins. All sera appeared to be HIV-negative on a third-generation ELISA. Specimens of these sera were also HIV-1-antigen negative and [by] PCR. Infection could not be detected after cocultivation of donor-derived lymphocytes with permissive cells. Furthermore, in a retrospective study of blood donations, seroconversion was not observed in any of the recipients of this blood. We performed a radioimmunoprecipitation assay (RIPA) using recombinant p24 proteins…No reaction was observed…herpes simplex virus type 1 (HSV-1), strain 17, may be the agent that caused the cross-reactivity in…two cases.”
Langedijk JP et al. Identification of cross-reactive epitopes recognized by HIV-1 false-positive sera. AIDS. 1992 Dec;6(12):1547-8.
“Forty-one peptides spanning the gag polyprotein precursor molecule (isolate HTLV-III/BH10;1) were synthesized. For length, peptides of 24 residues were selected, since these are able to form secondary structural motives and thus should allow not only the detection of antibodies directed to sequential epitopes but also of those directed to antigenic domains defined by structural properties to form alpha-helical, ß-pleated sheet or ß-turn protein regions…Reactivity of HIV-f sera When HIV sera were tested on the individual peptides considerable reactivity with values for optical density up to 0.5 was observed in some serum samples despite the fact that all those sera showed negative reactivity to gag products on Western blot and in immunofluorescence (Fig. 2; Table 1). The peptides, which showed such positive reactivity were identical to those preferentially recognized by HIV-1 positive sera. In addition, weak reactivities were identified to peptides 6 and 7, a region where HIV-1 positive sera were rather inactive…Testing HIV+ human sera for antibody reactivity with purified peptides derived from gag-specific protein sequences in order to define antigenic regions revealed a highly problematic picture: Consistent reactivity was observed to protein regions, which were recognized positively also by HIV~ sera, reactions to other peptides were highly diverse in the individual serum samples. This leads to the conclusion, that a sequential epitope is not present in gag proteins of HIV and the majority of specific antibodies is directed to structural domains on p24/p55 formed by protein interaction of the polyprotein precursor molecules leading to particle formation.”
Haist S et al. Reactivities of HIV-1 gag-derived peptides with antibodies of HIV-1-infected and uninfected humans. AIDS Res Hum Retroviruses. 1992 Nov 11;8(11):1909-17.
“A 30 year old male Hispanic college student with no history of intravenous drug abuse, blood tranfusion, or high risk sexual behavior was admitted to hospital in October 1990. He had had fever, myalgias, dyspnoea, weight loss, mouth ulcers, and arthritis in his leg for four months before admission…Antibodies to HIV were twice positive by ELISA at a one month interval. The western blot analysis gave positive results for the gp41 band…Six months later the ELISA and western blot results were negative…A 26 year old male Hispanic construction worker as diagnosed as having SLE in 1988 based on malar [cheek] rash, photosensitivity, persistent leucopenia and positive antibodies to DNA. He also developed sensitive polyneuropathy due to peripheral nerve vasculitis [so far this sounds like pesticide or heavy metal poisoning]…He did not report a history of intravenous drug abuse, blood transfusion, or high risk sexual behavior. He was being treated with prednisone 40 mg/day and monthly intravenous cyclophosphamide. In 1989 he was treated for pulmonary tuberculosis…admitted to hospital in August 1990 with fever, abdominal pain, weight loss, myalgias [muscle pain], and proximal and distal muscle weakness…The patient tested positive twice for antibodies to HIV by ELISA with a two month interval, but was negative by Western blot analysis. Six months later both tests were negative]”
Esteva MH et al. False positive results for antibody to HIV in two men with systemic lupus erythematosus. Ann Rheum Dis. 1992 Sep;51(9):1071-3.
“9 of the 10 case donors received influenza vaccine, compared with 3 of 30 control donors. Among 9 case donors, the mean time between vaccination and blood donation was 26 days (range, 9 to 68 days). Follow-up ELISAs of serum samples from seven case donors obtained 52 to 130 days after vaccination demonstrated reversion to HIV and HTLV-1 seronegativity in all but one specimen, with persistence of positive HCV ELISAs in four specimens. We estimate between 0.6% and 1.7% of blood donors who received influenza vaccine this season had multiple false-positive viral ELISAs.”
MacKenzie WR et al. Multiple false positive serologic tests for HIV, HTLV-1, and Hepatitis C following influenza vaccination. JAMA. 1992 Aug 26;268(8):1015-7.
“In 1990, of 20.2 million HIV tests done in Russia only 112 were confirmed and about 20,000 were false positives, 1991 saw some 30,000 false positives out of 29.4 million tests, with only 66 1991 alone some 8000 false-positive results were reported in pregnant women, with only 6 confirmations [presumably with the Western Blot test]
Voevodin A. HIV screening in Russia. Lancet. 1992;339:1548.
“In India, nearly 5000 blood donor specimens have shown serological evidence of HIV infection by [ELISA] but there are only a few reports of clinical evidence of [AIDS]. Majority continue to remain asymptomatic…During the period between March, 1989 and February, 1991, a total of 74 specimens were identified as positive for anti-HIV antibody by the method of competitive ELISA technique employing recombinant reagents. Out of 74 sera, 40 showed positivity by confirmatory Western Blot technique by the criteria of positivity laid down by CDC as well as WHO. Out of the remaining 34 specimens, 16 showed total absence of any band in Western Blot (false positive) while the remaining 18 specimens showed a few band(s) that could not qualify the interpretive criteria of positivity ('indeterminate' category)…our study did not point out any association between malarial infection and serological reactivity for HIV infection whether 'true' or 'false'.”
Chattopadhya D et al. Antimalarial antibody in relation to seroreactivity for HIV infection in sera from blood donors. J Commun Dis. 1991 Sep;23(3):195-8.
“The initial study group consisted of 1,129 addicts (949 men and 180 women) consecutively admitted to the National Institute of Mental Health’s former Clinical Research Center at Lexington, KY, between May 15, 1971, and May 14, 1972…The WB results from the earlier study, which had employed a technique enhanced by the use of an avidin-biotin system, were reanalyzed. The Centers for Disease Control issued diagnostic criteria in 1985 recommending that a WB be considered positive if either band p24 or band gp4l was present alone or in combination with other bands. On rereading, blots with isolated p24 bands were considered to be indeterminate. One 1985 WB, with bands at both the 24 and 55 kilodalton regions, was included among the positives, since the interpretation of this pattern had previously been unclear. The 1971-72 serum specimens were not available for retesting… The two former patients whose 1971-72 WB results were most strongly reactive had current ELISA and WB assays that were negative. Their immune function parameters were inconsistent with immune suppression… The results of the ELISA and WB assays performed on the 1971-72 specimens remain an enigma. Some were interpretable as positive, although only weakly reactive. One explanation is that the results observed in 1985 were true positives, that PDAs in the early 1970s had antibodies to an HIV-like agent that was nonpathogenic, and that the WBs subsequently converted from positive to negative. Loss of HIV antibodies in asymptomatic homosexual men has been reported. It is possible that antibodies to a nonpathogenic virus would have disappeared during the 17 to 18 years between admission to Lexington and the 1989 followup. Although this potential cannot be ruled out, it is more likely that the earlier results were false positives. The reasons for false positivity are unclear, but cross reactivity with related retroviruses may be one possibility. The HIV Western blot assay may cross-react with antibodies to HTLV-I in the p24 and p55 antigen regions, but not the gp4l region. These serum specimens were tested for the presence of HTLV-I/HTLV-II antibodies by other investigators, and a 6.3 percent seropositivity rate for the entire cohort was observed. It is not known if these 10 persons were seropositive for this related retrovirus; however, it is unlikely that this type of cross reactivity accounted for the previous results, given the distribution of the bands and the fact that reactivity was not detected during selected 1989 followup WB screening. The earlier false positivity could be the consequence of either the state of the serum specimens or the test kit or assay employed. It has been suggested that artifactual findings may occur as a consequence of frequent thawing and refreezing of serum aliquots, and that frequent refreezing might affect the physical properties and serologic characteristics of the serum protein moieties. The available evidence would suggest that long-term storage and repeated thawing and refreezing does not affect subsequent testing for serum constituents [the possibility that the 1971-72 Western Blot results were valid and were due to exposure to IV drugs, was not considered, nor was the possible explantion for later survival and negative HIV tests being removal of exposure to IV drugs]
Lange WR et al. Followup study of possible HIV seropositivity among abusers of parenteral drugs in 1971-72. Public Health Rep. 1991 Jul-Aug;106(4):451-5.
“The initial study group consisted of 1,129 addicts (949 men and 180 women) consecutively admitted to the National Institute of Mental Health’s former Clinical Research Center at Lexington, KY, between May 15, 1971, and May 14, 1972…The WB results from the earlier study, which had employed a technique enhanced by the use of an avidin-biotin system, were reanalyzed. The Centers for Disease Control issued diagnostic criteria in 1985 recommending that a WB be considered positive if either band p24 or band gp4l was present alone or in combination with other bands. On rereading, blots with isolated p24 bands were considered to be indeterminate. One 1985 WB, with bands at both the 24 and 55 kilodalton regions, was included among the positives, since the interpretation of this pattern had previously been unclear. The 1971-72 serum specimens were not available for retesting… The two former patients whose 1971-72 WB results were most strongly reactive had current ELISA and WB assays that were negative. Their immune function parameters were inconsistent with immune suppression… The results of the ELISA and WB assays performed on the 1971-72 specimens remain an enigma. Some were interpretable as positive, although only weakly reactive. One explanation is that the results observed in 1985 were true positives, that PDAs in the early 1970s had antibodies to an HIV-like agent that was nonpathogenic, and that the WBs subsequently converted from positive to negative. Loss of HIV antibodies in asymptomatic homosexual men has been reported. It is possible that antibodies to a nonpathogenic virus would have disappeared during the 17 to 18 years between admission to Lexington and the 1989 followup. Although this potential cannot be ruled out, it is more likely that the earlier results were false positives. The reasons for false positivity are unclear, but cross reactivity with related retroviruses may be one possibility. The HIV Western blot assay may cross-react with antibodies to HTLV-I in the p24 and p55 antigen regions, but not the gp4l region. These serum specimens were tested for the presence of HTLV-I/HTLV-II antibodies by other investigators, and a 6.3 percent seropositivity rate for the entire cohort was observed. It is not known if these 10 persons were seropositive for this related retrovirus; however, it is unlikely that this type of cross reactivity accounted for the previous results, given the distribution of the bands and the fact that reactivity was not detected during selected 1989 followup WB screening. The earlier false positivity could be the consequence of either the state of the serum specimens or the test kit or assay employed. It has been suggested that artifactual findings may occur as a consequence of frequent thawing and refreezing of serum aliquots, and that frequent refreezing might affect the physical properties and serologic characteristics of the serum protein moieties. The available evidence would suggest that long-term storage and repeated thawing and refreezing does not affect subsequent testing for serum constituents [the possibility that IVDUs survived for so long and became HIV-negative was due to them stopping injecting drugs was not considered. The one death among the 10 WB positives was due to a traffic accident, and the man had gained considerable weight, possible evidence of a healthier lifestyle]
Lange WR et al. Followup study of possible HIV seropositivity among abusers of parenteral drugs in 1971-72. Public Health Rep. 1991 Jul-Aug;106(4):451-5.
“HIV-1 p24 is the HIV-1 protein most prone to "false-positive" reactions…false-positive reactions have been observed with every single HIV-1 protein”
Ng V. Serological diagnosis with recombinant peptides/proteins. Clin Chem. 1991;37(10):1667-8.
“In this study we have shown that normal human serum contains antibodies capable of recognizing the carbohydrate moiety of HIV envelope glycoproteins…These antibodies are thought to have been naturally elicited as a result of exposure of various pathogens including bacteria, fungi, and human viruses with envelope glycoproteins such as herpes viruses. It is unlikely that individuals whose sera posses anti-oncovirus antibodies are infected with animal retroviruses…Antibodies reactive to HIV glycoproteins described here may also have been elicited naturally rather than as a consequence of HIV exposures.”
Tomiyama T et al. Recognition of human immunodeficiency virus glycoproteins by natural anti-carbohydrate antibodies in human serum. Biochem Biophys Res Commun. 1991 May 31;177(1):279-85.
“A 25-year-old nurse injured her hand on the edge of an operating-table. She was given a prophylactic injection of tetanus immune globulin. The following day a blood sample was taken to test for hepatitis B markers and HIV antibody…HBV markers were negative but she was anti-HIV positive with both ELISA tests used in our laboratory, and the same sample was western blot positive, showing reactivity against all viral proteins…A second blood sample, taken 12 days later, was anti-HIV negative by ELISA but showed reactivity for gp120 and p24 by western blot. A third sample, taken 1 month after the first, was negative by both ELISA and western blot”
Gonnelli A et al. Transiently positive HIV antibody test after treatment with tetanus immune globulin. Lancet. 1991 Mar 23;337(8743):731.
“The possibility of false-positive results in the Ag [p24 antigen], IVAP [in vitro antibody production] and PCR [‘viral load’] assays seems worth stressing. False-positive results in Ag and IVAP occurred only in the first 2-3 months of life [in this relatively small study]…false positive PCR results were unrelated to the child’s age.”
De Rossi A et al. Antigen detection, virus culture, polymerase chain reaction, and in vitro antibody production in the diagnosis of vertically transmitted HIV-1 infection. AIDS. 1991 Jan;5(1):15-20.
“As part of a phase 1 trial of a candidate AIDS vaccine, blood specimens were collected from 168 healthy adult volunteers at minimal or no risk for becoming infected with human immunodeficiency virus type 1 (HIV-1). These specimens were screened for evidence of HIV-1 infection by enzyme immunoassay (EIA) and the Biotech/Du Pont Western blot (168), culture (122), and polymerase chain reaction assay (20). None of the subjects had a positive test result by any of these assays, but 32% had indeterminate Western blot tests, most of which demonstrated a single band of low intensity. The most common bands were p24 (47%), p55 (34%), and p66 (36%); envelope bands were unusual (gp41, 2%; gp120, 2%) [meaning that none of these bands are unique to HIV, yet multiple bands would be interpreted]. No serum specimen collected after 2-11 months from individuals with indeterminate Western blot results was positive by EIA or Western blot. There was 91% agreement in the test results of the first and second serum samples when the same lot of Western blot kit was used but only 36% agreement when different lots were used.”
Midthum K et al. Frequency of indeterminate Western Blot tests in healthy adults at low risk for HIV infection. J Infect Dis. 1990 Dec;162(6):1379-82.
“144 dog sera were tested on Chiron Western blot strips. Of these, 72 sera (50%) reacted with one or more HIV recombinant proteins”
Strandstrom HV et al. Studies with canine sera that contain antibodies which recognize human immunodeficiency virus structural proteins. Cancer Res. 1990 Sep 1;50(17 Suppl):5628-5630.
“A 31-year-old heterosexual male, who was not a drug abuser, was admitted with a history of an influenza-like illness followed some 6 weeks later by a painful neuropathy progressing from legs to hands…autoantibodies were noted to be positive on one or more occasions (double-stranded DNA, smooth muscle, and ANCA). ANCA was detected by routine immunofluorescence with alcohol-fixed neutrophils; staining was perinuclear with some focal intracytoplasmic positivity. Subsequently HIV antibody was detected in three sera, confirming the diagnosis of HIV-induced neuropathy. The history and clinical findings followed the pattern described with HIV seroconversion. [The doctors concluded that the auto-antibody tests were false-positive, but since neuropathy is not an AIDS-defining illness (but a side-effect of AIDS drugs) and flu-like symptoms are vague, it’s equally possible that the positive HIV tests were false]
Davenport A, Grant PJ. False-positive autoantibodies in HIV infection. Lancet. 1990 Aug 4;336(8710):317-8.
“Three commercial antibody EIAs were used. The distribution of reactivities in the nine sera with p24 bands in HIV-I EIB can be seen in Table 2. Five sera reacted only in the whole virus EIA, while two reacted only in the recombinant HIV-l antibody EIA…Cross-reactions with nonretroviral antigens which could be caused by molecular mimicry (eI, Ref. 21), inadvertent immunization with alimentary animal retroviruses such as bovine immunodeficiency virus,? or putative new human retroviruses could be the basis of the described p24 ± p55 reactions. If the latter is the case, such virus(es) should be relatively apathogenic. Judging from the reasons for HIV antibody testing (blood donation, pregnancy), the persons who donated the indeterminate HIV-1 + sera probably were healthy. This is in accord with the observations of others. 22 The phenomenon of false positive HIV p24 antibodies is not confined to humans. They also occur in rabbits and goats. 10 The responsihle antigen(s) thus may be rather widespread.”
Blomberg J et al. Identification of regions of HIV-1 p24 reactive with sera which give indeterminate results in electrophoretic immunoblot with the help of long synthetic peptides. AIDS Res Hum Retro. 1990;6:1363-72.
“Clinical follow-up of patients with indeterminate Western blot results may require many months of observation, interviewing, and testing…Some indeterminate results may be obtained with serum samples from persons who are in the process of seroconverting…A person whose Western blot test results continue to be consistently indeterminate for at least 6 months–in the absence of any known risk factors, clinical symptoms, or other findings–may be considered to be negative for antibodies to HIV-1. Such persons should be reassured that they are almost certainly not infected with HIV-1. However, no large-scale studies have been done to provide virologic data to confirm independently the serologic findings from the studies of clients whose Western blot test results are consistently indeterminate. In contrast, an asymptomatic person who has an indeterminate Western blot test result and a history of possible exposure to or symptoms compatible with HIV infection requires additional diagnostic follow-up. This should include conducting serial Western blot testing, assessing the function of the individual’s immune system, and eliciting the cooperation of the person’s sexual and needle-sharing partners to determine whether they are infected. Individuals with a pattern of indeterminate Western blot test results should not donate blood or plasma for either transfusion or use in manufactured blood products.”
CDC. Interpretation and Use Of Western Blot Assay for Serodiagnosis of Human Immunodeficiency Virus Type 1 Infections. MMWR. 1989;38(S-7):1-7.
“We describe a patient with acute leukemia in whom both antibodies against HLA-DR4 and a false-positive HIV ELISA transiently occurred while he was receiving red-cell and platelet transfusions…The patient’s serum first became reactive with H9 ELISA reagents in September 1985. ELISA values rose until November and then fell. The immunofluorescence assay was also positive during this period, but reactivity was similar with both infected and noninfected H9 cells…none of the serum samples tested reacted the CEM-cell ELISA kit, and Western blot analyses of serum samples obtained in November were negative…Serum samples obtained in November 1985 were retested…and were again positive”
Yu SK, Fong CKY, Landry ML. A false positive HIV antibody reaction due to transfusion-induced HLA-DR4 sensitization. N Engl J Med. 1989 Jun 1;320(22):1495.
“Two newborns of mothers carrying hepatitis B and at high risk for human immunodeficiency virus (HIV) infection developed HIV-positive test results by enzyme-linked immunosorbent assay and Western blot tests after birth. Both had been administered hepatitis B immune globulin within 48 hours of birth. Serological tests detected HIV antibody as long as 17 days after birth. Both newborns had received lots of hepatitis B immune globulin containing antibody to HIV.”
Schlech WF 3rd et al. Passive transfer of HIV antibody by hepatitis B immune globulin. JAMA. 1989 Jan 20;261(3):411-3.
“Two newborns of mothers carrying hepatitis B and at high risk for human immunodeficiency virus (HIV) infection [but actually HIV negative] developed HIV-positive test results by enzyme-linked immunosorbent assay and Western blot tests after birth. Both had been administered hepatitis B immune globulin within 48 hours of birth. Serological tests detected HIV antibody as long as 17 days after birth. Both newborns had received lots of hepatitis B immune globulin containing antibody to HIV. While hepatitis B immune globulin cannot transmit HIV infection to recipients, physicians should be aware that administration of older lots of this preparation may result in transiently positive tests for HIV antibody in the recipients”
Schlech WF 3rd et al. Passive transfer of HIV antibody by hepatitis B immune globulin. JAMA. 1989 Jan 20;261(3):411-3.
“5 recipients [of organ transplants] not reported above each had only a single serum positive by EIA [ELISA antibody test] but negative by Western Blot [antibody test]…3 patients who had positive Western blot tests are not listed…because later serum samples did not contain HIV-1 antibodies”
Dummer JS et al. Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986. Transplantation. 1989 Jan;47(1):134-40.
“The pattern of bands on protein or Western immunoblot (IB) for antibodies to antigens of human immunodeficiency virus (HIV) is not always reproducible…positivity may be simulated by the reactivity of serum with nonviral proteins of molecular sizes similar to viral components. Finally, technical vagaries may result in apparent rather than real loss of antibody to HIV capsid antigen (p24)…Routine Quality Control with Two Positive QC specimens…Only 101 (56%) of the 179 assays showed the presence of p24, p32, and gp41 and/or gp120, a pattern that would be reported as positive by all sets of criteria in use at reference laboratories…Routine Quality Control with Two Negative QC Specimens…An absence of all bands…was reported for only 67 assays (67%) [i.e. 33% of tests on negative western blot controls showed one or two positive bands]…Physicians should remember that any given IB result can be erroneous and seek further confirmation by a later sample if applicability of the result to the patient seems questionable. The criteria for positivity when only some bands are seen continues to be a problem. Reactivity at either p24 or gp41, without p32 or gp120 has sometimes been considered adequate for confirmation of anti-HIV positivity. This pattern was seen 10 times with one of the positive samples inn two laboratories but a combined total of 19 times in three laboratories with the two negative samples. It is obvious that p24 alone or gp41 alone, without p32 or gp120, must be reported as indeterminate and the IB repeated on the same or a subsequent specimen. On the other hand, requiring three bands among p24, p32, and gp41 or gp120 would have permitted a positive interpretation of only 101 or 179 assays (56%) of QC(+) [positive quality control] specimens. Requiring two of the three would result in a correct interpretation for 166 of 179 (93%) assays of QC(+) samples and 99 of 101 (98%) assays of QC(-) specimens. The criteria for positivity and negativity for any given IB assay, however, must minimize false positivity and false negativity, even if reassay of specimens is necessary for a moderate number of sera. An indeterminate pattern (i.e.,, not interpretable as necessarily positive or negative) tended to occur in clusters on a given day of testing or on successive dates, particularly for the negative QC samples. This seems attributable to a systematic technical problem at that particular time. Whenever we observed this occurrence, we resubmitted to the same facility after discussion of the problem or checked reproducibility in another laboratory.”
Edwards VM, Mosley JW. Reproducibility in quality control of protein (Western) immunoblot assay for antibodies to human immunodeficiency virus. Am J Clin Pathol. 1989 Jan;91(1):75-8.
“we describe a patient whose serum showed false-positive reactions with HIV proteins detected by ELISA and immunoblot assay with an unusual reaction pattern…The patient…was heterosexual, married and had one child. The wife and the child were seronegative on HIV ELISA. To obtain anti-Rhesus immune plasma the patient was given six 5 ml injections of Rh+ serum, administered at 4-day intervals, Rh+ serum was shown to be negative on HIV antibody and antigen ELISA…Blood taken after the first immunization was shown to be negative on HIV antibody ELISA and immunoblot assay [Western Blot]. After the second immunization a weak signal on ELISA, slightly above the cut-off level, was monitored. After the third immunization the signal was strong and immunoblot revealed distinct interaction with p17 and p55 proteins. An even stronger signal was monitored after the fifth immunization. Interaction with p17, p31, gp41, p55 and some other proteins was evident. However…immunofluorescence…gave negative results. The samples were also probed in immunoblot based on HIV gag and env encoded proteins expressed by recombinant vaccinia viruses. They demonstrated no reaction with recombinant HIV proteins…A specimen is considered to be immunblot-reactive by the presence of bands at the 24-kilodalton [p24] and/or 41-kilodalton [gp41] molecular weight regions with or without the presence of other bands. Reaction with isolated p17, p24 or p55 proteins may be false-positive while interaction with gp41 is considered indicative of HIV infection. Here we present evidence that this may be untrue. What is more, analysis of sequential samples of the serum demonstrated blot progression imitating real HIV infection.”
Bukrinsky MI et al. Reactivity to gag- and env-related proteins in immunoblot assay is not necessarily indicative of HIV infection. AIDS. 1988 Oct;2(5):405-6.
“At the time of study (1978-1983), 36 (33%) of the 110 patients had been exposed to HIV, based on positive Western blot analysis…False-positive ELISA reactions for anti-HIV in relation to Western blot were seen in five (7%) of the 70 patients with negative Western blot analyses [and significant discrepancies between the two ELISA types used…Compared with the patients with a true-negative ELISA for anti-HIV, patients with false-positive tests had significantly more years of alcohol abuse and commenced their alcohol use at younger ages…no specific liver pathology was associated with a false-positive ELISA test for HIV”]
Novick DM et al. Specificity of antibody tests for human immunodeficiency virus in alcohol and parenteral drug abusers with chronic liver disease. Alcohol Clin Exp Res. 1988 Oct 5;12(5):687-90.
“we found cross-reacting HIV-1 in patients with multiple sclerosis. Among 150 healthy Finnish persons, 1 (a woman) had antibodies to p24 and p55 of HIV-1. Some patients with multiple sclerosis, cutaneous T-cell lymphoma, or dermatologic disorders had antibodies that also reacted with the viral proteins of an HIV-2 isolate”
Ranki A, Johansson E, Krohn K. Interpretation of antibodies reacting solely with human retroviral core proteins. N Engl J Med. 1988;318:448-9.
“Most patients (68 to 89%) from low risk groups (prevalence of 0.1% or less) who show reactivity on screening tests will have false-positive results…The predictive value of a positive ELISA varies from 2 to 99%…One notable association with false positive ELISA reactivity in some commercial preparations has been patients with anti-HLA-DR4 antibodies, most often multiparous [having experienced one or more births] or multiply transfused patients”
Steckelberg JM, Cockerill F. Serologic testing for human immunodeficiency virus antibodies. Mayo Clin Proc. 1988;63:373-9.
“if a specimen is reactive in several assays based on independent methodologies [since ELISA and Western Blot are both antibody tests, they cannot be considered independent, nor can several repeated ELISA even if done by different personnel], it is very likely [but not certain, is that good enough for you?] to be truly positive.”
Mortimer PP. The AIDS virus and the HIV test. Med Int. 1988;56:2334-9.
“Four asymptomatic homosexual men reverted from positive to negative serologic [antibody] results for…HIV-1…over 2.5 years as shown by …ELISA…and Western Blot…No HIV-1-p24 antigenemia was detected; cryopreserved [frozen] peripheral blood mononuclear cells [PBMCs] were negative for HIV-1 by standard culture assay. Polymerase chain reaction…assays were done on [PBMCs] and showed the HIV-1 provirus in all subjects 6 to 18 months after the last positive antibody test…[this is in the abstract, but in the body of the paper they say]…The [PCR]-amplified gag gene product was found [in patient A] at visits one to four…[and] at visits two, three and four [in patient B][and] at visits one and two but not at three and four [in patient C][and] at visits one and three but not at visits four and five [in Patient D][But, in the table of data they show the actual data for the four tests they took at 6 month intervals. Omitting times when they did not test a sample, for patient A the results were at 6mo–2 of 4 determinations positive, 1yr–1 of 4, 1.5yr–3/4 positive, 2yr–4/4 +. Patient B: 1yr–2/4, 1.5yr–1/4, 2yr–2/4. Patient C: 6mo–1/4, 1yr–2 of 4, 1.5yr–0/4, 2yr–0/4. Patient D: 6mo–4/4, 1.5yr–1/4, 2yr–0/4, 2.5yr–0/4]
Farzadegan H et al. Loss of human immunodeficiency virus type 1 (HIV-1) antibodies with evidence of viral infection in asymptomatic homosexual men. A report from the Multicenter AIDS Cohort Study. Ann Intern Med. 1988 Jun;108(6):785-90.
“Lymph nodes from the PGL [persistent generalized lymphadenopathy - swollen lymph nodes] group [of people believed at risk of AIDS] were characteristically enlarged…In 11 of these 18 lymph nodes, occasional particles were identified that measured approximately 100 nm in diameter with well-delineated outer limiting membranes surrounding central to eccentric predominantly round electron-dense cores [i.e. the size, shape and structure of HIV][however] in 7 of 18…no cored particles were identified despite an intensive search. In two of the 20 PGL lymph nodes neither type of particle [with or without cores] were found…[we also studied] non-HIV related reactive lymph nodes [although all the people from which samples were taken were assumed to be HIV-negative, none were actually tested]. Of major significance was the finding of viral-like particles, morphologically [i.e. size, shape and structure] indistinguishable from those observed in PGL…cored particles were seen in 8 of the 15 lymph nodes…The results of this study compel us to conclude that, while the particles observed in PGL lymph nodes are indeed HIV [because 19/20 had anti-p24 staining, while none of the non-HIV lymph nodes did], morphologically similar particles can be seen in other reactive conditions, and the presence of such particles do not, by themselves, indicated infection by HIV. Clearly, techniques that demonstrate the presence of specific viral antigens or viral RNA are needed to supplement ultrastructural observations [or even actual isolation of the putative virus]
O'Hara CJ et al. The ultrastructural and immunohistochemical demonstration of viral particles in lymph nodes from human immunodeficiency virus-related and non-human immunodeficiency virus-related lymphadenopathy syndromes. Hum Pathol. 1988 May;19(5):545-9.
“8 of the 11 false-positive samples were from women who had at one time been pregnant…other reported causes of false positive ELISA tests for HIV screening include anti-hepatitis A IgM, anti-hepatitis B core IgM, anti-thyroid microsomal, antinuclear, anti-smooth muscle, anti-parietal cell, anti-liver/kidney microsomal, and anti-mitochondrial…Causes of false positive Western blot tests for antibodies to HIV are…1. Presence of antibody to another human retrovirus…2. Presence of another human retrovirus in the H9 cells that the reagent antigen is obtained from. 3. Cross reactions with cell derived ribonucleoproteins or other non-viral proteins…Monoclonal [artificial] antibodies can be a pure, well defined and characterized reagent used to detect the HIV virus. These antibodies do, however, show cross reactivity with other antigens…1. Proteins found in HIV particles may be part of normal cellular polypeptides that are expressed only under particular circumstances, such as rapid cell proliferation where cellular polypepetides are entrapped with genuine HIV components. 2. Whole polypeptides which are unrelated but share short amino acid sequences with HIV sequences with HIV can give rise to immunologic cross reactions…3. Proteins encoded by the HIV genome and gene products of the human endogenous gag sequences are related to the extent that monoclonal antibodies react with both.”
Houn HY et al. Status of current clinical tests for human immunodeficiency virus (HIV): applications and limitations. Ann Clin Lab Sci. 1987 Sep-Oct;17(5):279-85.
“Here we describe an AIDS-related serum autoantibody that reacts with an antigen of relative molecular mass 18,000 (Mr 18K) restricted to lectin-stimulated or HIV-infected CD4+ T cells. The antibody also suppresses proliferation of CD4+ T cells in vitro and induces cytotoxicity of these cells in the presence of complement. Its role in the development of AIDS merits attention.”
Stricker RB et al. An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells. Nature. 1987 Jun 25-Jul 1;327(6124):710-3.
“Twenty-six sera containing anti-HIV antibodies from individuals with AIDS, AIDS-related complex, lymphadenopathy syndrome, or from seropositive individuals without clinical symptoms, were tested for the presence of natural autoantibodies (NAb) to actin, DNA, tubulin, thyroglobulin, albumin, myosin and TNP-BSA. Sera from 22 seronegative individuals at high risk for HIV infection were also examined. NAb titres to all these antigens were found to be elevated in both groups as compared to the titres in pooled normal human sera. The most prevalent NAb were those of the IgG class directed against TNP found in high titre in seropositive individuals. On the basis of the above results, sera from 50 anti-HIV-positive and 67 anti-HIV-negative individuals were tested for IgG antibody activity against a panel of protein antigens with different degrees of TNP substitution. The greater the TNP substitution, the higher the titres of IgG antibodies detected in anti-HIV-positive sera. Antibody titres in seronegative individuals at high risk for HIV infection were independent of the degree of TNP substitution. In almost all cases, the highest titres of IgG anti-TNP antibodies were found in anti-HIV-positive sera from individuals with clinical manifestations.”
Matsiota P et al. Detection of natural autoantibodies in the serum of anti-HIV-positive individuals. Ann Inst Pasteur Immunol. 1987 Mar-Apr;138(2):223-33.
“A 55-year-old asymptomatic woman was advised by the Montreal Red Cross that she was seropositive for HIV, as determined by an enzyme-linked immunosorbent assay (ELISA) and confirmed by a Western blot test. The most probable source of contamination was her husband, who had received 3 units of blood while undergoing surgery in our hospital two years previously. The husband’s serum was sent to our laboratory, but no antibodies against HIV were detected by either ELISA or indirect immunofluorescence. At the same time, we confirmed the apparent positivity of the patient’s serum both by ELISA and by an indirect immune-fluorescence test, in which H9 cells, infected by the human T-cell lymphotropic virus type IIIB strain of HIV, are used as targets. Reactivity on the latter test partially disappeared after pre-absorption of the patient’s serum with non-infected H9 cells. We pursued the search for HIV-specific antibodies in the husband’s serum by the Western blot test, using both non-infected and infected H9 cells. We screened the patient’s serum in the same way. The Western blot test failed to detect antibodies against viral proteins in the husband’s serum. These results, supported by previous reports of false seropositivity in asymptomatic blood donors, emphasize the need to be certain of viral antigen specificity when screening for HIV antibodies. We suggest that blood banks use both HIV-infected and non-infected cell lines when confirming seropositivity by the Western Blot test and that the presence of bands on such tests not be automatically considered to indicate positive status”
Roy S et al. Need for caution in interpretation of Western blot tests for HIV. JAMA. 1987 Feb 27;257:1047.
“we tested 151,667 blood units by ELISA. 130 (8.6%) were confirmed positive by WB (in that they reacted with different HIV proteins, including gp41 and/or gp 110). 8 of these were false positive for gp18 and 23 were false positive for p25 [now known as p24]; in other words there was 1 false positive by WB for about 4 true positives in our population of blood donors and under our work conditions”
Couroucé A-M et al. False-positive Western blot tests reactions to human immunodeficiency virus in blood donors. Lancet. 1986 Oct 18;328(8512):921-2.
“the C+ M- [child HIV-positive, mother negative] children were significantly more likely to be boys, to have received medical injections, and to have had previous blood transfusion or hospital admission than C- M- children…Gastrointestinal illness and malnutrition were associated with seropositivity among ill children”
Mann JM et al. Risk factors for human immunodeficiency virus seropositivity among children 1-24 months old in Kinshasa, Zaire. Lancet. 1986 Sep 20;2(8508):654-7.
“The frequencies of false-positive reactions in a tricky panel of samples from patients with autoimmune and acute viral diseases...were Abbott 9.5%...Organon 1.7%...Litton 1.0%...Behring 2.7%...Wellcome 0%...and Pasteur 0%...The results of a 7th EIA (Dupont) were excluded from the study at the company’s request.”
Reesink HW et al. Evaluation of six enzyme immunoassays for antibody against human immunodeficiency virus. Lancet. 1986 Aug 30;328(8505):483-6.
“Reactivity with [HIV proteins] p24 and/or gp41 has been suggested as a minimum requirement for HIV seropositivity by WB [Western Blot]. While testing ELISA positive serum from Swedish blood donors we detected 3 sera with false-positive WB reactions to p24 and p55...The 3...had no risk factors for HIV infection”
Biberfeld G et al. Blood donor sera with false-positive western blot reactions to human immunodeficiency virus. Lancet. 1986 Aug 2;328(8501):289-90.
“we recently sent 5 identical proficiency panels to 5 large commercial firms that offered HTLV-III Western blot testing…Each panel consisted of 15 samples from healthy, low risk adults whose serum was repeatedly negative for HTLV-III antibodies and 5 samples from HTLV-III-infected (culture-documented) patients…4 of the 5 laboratories reported at least one false-positive test result. The 6 false positive results were all on different normal specimens…The single most common error was detection of a band at 24 kd using normal samples.”
Burke DS, Redfield RR. False-positive western blot tests for antibodies to HTLV-III. JAMA. 1986 Jul 18;256(3):347.
“We recently completed a study of 1129 serum samples obtained from parenteral [IV] drug abusers throughout the United States and 89 control samples from nonabusers of drugs, all collected during 1971-1972…A total of 45 serum samples from addicts were repeatedly positive according to at least one of the ELISA procedures, whereas the 89 control samples were uniformly negative…these samples and 196 other selected samples, including 3 randomly selected control samples, were tested by the Western blot technique. 17 of the serum samples from addicts demonstrated reactivity to specific HTLV-III [HIV] proteins. The 3 control samples were negative…14 of the samples from addicts demonstrated reactivity to multiple viral proteins on the blot, and 3 reacted with only the p24 protein…On the basis of our positive Western blot data, it appears possible that parenteral drug abusers may have been exposed to HTLV-III or a related virus as early as 1971. An alternative but equally viable explanation is that the HTLV-III seropositivity detected in these specimens represents false positive or nonspecific reactions. Parenteral drug abusers are known to present a high rate of both false positive and false negative results on ELISA…often have hypergammaglobulinemia, higher titers of immune complexes, a high prevalence of positive tests for rheumatoid factor, and high rates of false positivity on a number of routine laboratory tests.”
Moore JD et al. HTLV-III seropositivity in 1971-1972 parenteral drug abusers--a case of false positives for evidence of viral exposure?. N Engl J Med. 1986 May 22;314(21):1387-8.
“We evaluated serum samples from a group of 12 patients with acute Plasmodium vivax infection [malaria] who lived in…southwestern Venezuela…Our second group, 12 patients with Plasmodium falciparum infection…None of the patients were receiving antimalarial drugs…and none belonged to any of the recognized AIDS risk groups or had any AIDS-associated disorders…3 of the patients with P. falciparum infection (25%) and 5 with P. vivax (41%) were found to be positive for HTLV-III/LAV [HIV] antivodies by [3 antibody test types]
Volsky DJ et al. Antibodies to HTLV-III/LAV in Venezuelan patients with acute malarial infections. N Engl J Med. 1986 Mar 6;314(10):647-8.
“Initial testing...revealed that [a 34-year old woman from rural Alabama] was positive for HTLV-III [HIV] antibody by ELISA tests on two separate occasions. Here serum was then sent for verification to the designated commercial laboratory, where three repeat ELISAs were strongly was a Western blot assay...In July 1985, the patient was informed that her serum was positive for HTLV-III antibody...Her physical examination was normal. Both she and her husband of 14 years denied any homosexual or extramarital sexual encounters, intravenous drug abuse, blood transfusions, or foreign travel. The patients T4:T8 [immune cell] ratio was 2.1:1, with a normal lymphocyte count. Her husband and their two-year-old son were both antibody negative by ELISA. More blood was drawn from the patient...Western blot, radioimmunprecipitation, and HTLV-III virus isolation studies were all negative. HTLV-III ELISAs were repeated in two laboratories, and results from both were positive...Western blot tests with positive bands at 24 and 41 kd [which this woman had, plus two others] have been used as the ‘gold standard’ by which other test results are judged to be falsely positive. Several articles refer to the inevitability of false positive Western blots.”
Saag MS, Britz J. Asymptomatic blood donor with false-positive HTLV-III western blot. N Engl J Med. 1986 Jan 9;314(2):118.
“We tested serum samples from 224 [Venezuelan] Indians belonging to four different ethnic groups…5 of 150 Yanoama Indians, 2 of 54 Makiratare Indians, and 2 out of 15 Pemon Indians were positive for HTLV-III/LAV [HIV] antibodies by all three assays used…all the Indians tested were apparently healthy…Amazonian Indians have no contact with surrounding non-Indian populations…[they are located] in the most inland and remote part of the country, thereby making transmission of agents from outside of the Continent unlikely; blood donors in Caracas and other coastal cities facing the Caribbean islands, on which AIDS is endemic, lack antibodies against HTLV-III/LAV; no AIDS case from Venezuela has yet been reported…Despite a prevalence [in aboriginal populations]…of up to 13%, no clinical symptoms of AIDS-like illness were observed during the latest blood collection round in 1984/85.”
Rodriquez L et al. Antibodies to HTLV-III/LAV among aboriginal Amazonian Indians in Venezuela. Lancet. 1985 Nov 16;326(8464):1098-100.
“The prevalence of malarial parasitaemia was 13% [in a serological survey of 250 outpatients in rural Zaire]. However, 72% of patients had antibodies against P falciparum [the malaria parasite]…The proportions of subjects positive in the ELISA test for HTLV-I, HTLV-II and HTLV-III [HIV] were 14%, 25% and 12%, respectively…When the titer [level] of antibodies against P falciparum was considered…this single factor dominated all others…If the human retrovirus reactivity observed in the ELISA tests is frequently non-specific among Africans, the causes of the non-specificity need to be clarified.”
Biggar RJ et al. ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet. 1985 Sep 7;326(8454):520-3.
“68% to 89% of all repeatedly reactive ELISA tests are likely to represent false positive results...each year we might expected to find 175 to 209 truly antibody-positive donors [in Minnesota] and between 371 and 1701 falsely positive donors among those who have repeatedly positive screening tests”
Osterholm MT et al. Screening donated blood and plasma for HTLV-III antibody: facing more than one crisis?. N Engl J Med. 1985;312:1185-8.
“the proportion of HTLV-III [HIV] seropositive patients was notably high among those with idiopathic splenomegaly [enlarged spleen with no known cause] and schistosomiasis [parasitic infection]…Among Kenyans, the Turkana have the highest and the [closely related] Masai have the lowest prevalence of antibodies against both viruses [HTLV-I and HTLV-III(HIV)]…the Turkana inhabit a desolate area of desert and scrub-brush and are the poorest and most isolated of the groups that we studied…the Turkana have many other parasitic and viral infections [apart from seasonal malaria], including one of the highest rates of hydatid [tapeworm] disease in the world and a high prevalence of hepatitis markers…In view of the high prevalence of HTLV-III antibody, AIDS illness might have been expected to be frequent, yet no cases have been documented in Kenya [to 1985]. We are aware of only 3 cases suspected of being AIDS-related…it is unlikely that AIDS-illnesses of the recognized varieties are occurring at a rate commensurate with the prevalance of antibody against HTLV-III”
Biggar RJ et al. Regional variation in prevalence of antibody against human T-lymphotropic virus types I and III in Kenya, East Africa. Int J Cancer. 1985 Jun 15;35(6):763-7.
“We have tested HLA antisera in the Abbott ELISA [HIV antibody test]…of 310 HLA-DR antisera 10 gave positive HTLV-III antibody results. The HTLV-III [HIV] antibody ELISA [antibody test] from Electro-Nucleonics Inc.…also gave positive results with [10 out of 310] HLA-DR4 antisera except for 9w594…the recognition of DR4 antibodies in the sera of homosexuals (immunised by sperm and white blood cells), haemophiliacs, and patient on haemodialysis is important in the interpretation of [potentially false] positive HTLV-III antibody ELISA results.”
Kühnl P et al. HLA DR4 antibodies cause positive HTLV-III antibody ELISA results. Lancet. 1985 May 25;1(8439):1222-3.
“Three chimpanzees were inoculated with AIDS plasma [i.e. plasma from someone with AIDS, not purified virus] and one was inoculated only with normal human plasma. Blood was sampled biweekly from each animal and sperm was tested in the standard indirect ELISA for HTLV-III [HIV] antibodies...all four of the animals were positive for passively transferred HTLV-III”
Saxinger WC, Gallo RC. Competitive ELISA for the detection of HTLV-III antibodies. USPTO. 1985 May 24;4,661,445.
“The Ugandan serum tested was primarily from clinically healthy donors randomly selected as controls [for an unrelated study]…All [blood] samples were collected between August 1972 and July 1973…The data show that antibodies recognizing a virus related to or identical to HTLV-III [HIV] were present in most of the Ugandan subjects tested…our samples were taken from a sparsely populated subsistence-farming environment where AIDS is not known to occur, while the recent spread in African AIDS appears to be in more densely populated urban environments [but apparently the thought that the antibodies were non-specific for HIV never crossed the minds of these researchers]
Saxinger WC et al. Evidence for exposure to HTLV-III in Uganda before 1973. Science. 1985 Mar 1;227(4690):1036-8.
“False positive and false negative results are to be expected [in HIV antibody testing] as with all screening tests”
Landesman SH et al. The AIDS epidemic. N Engl J Med. 1985 Feb 21;312(8):521-4.
[during validation tests for HIV ELISA antibody tests] any positive ELISA screening result among the blood donors could be assumed to represent “false-positives” [but, if this same person later had the same test outside the context of a validation study, it would be assumed to be a true positive!]
Weiss SH et al. Screening test for HTLV-III (AIDS agent) antibodies: specificity, sensitivity, and applications. JAMA. 1985 Jan 11;253(2):221-5.
“non-specific reactions may be seen in samples from some people who, due to prior pregnancy, blood transfusion, or other exposure, have antibodies to the human cells or media in which the HIV-1 virus used for the manufacture of [this test] is grown…”
Summary basis of approval: Genetic Systems rLAV EIA. Genetic Systems Corporation.
“Clinical samples have also been described have…been described that are reactive in the screening assays but do not contain HIV-1 antibody. Some of these samples possess antibody to certain Class II HLA histocompatibility antigens that are found in some cell lines used to produce the virus. Other persons, who have had no known exposure to HIV-1, produce reactive results in the screening test for still unknown reasons. Such nonspecific results are found commonly when screening tests are used in large populations. Since the psychosocial and medical implications of a positive antibody test may be devastating, it has been recommended that additional testing be performed on such samples [such as this test]…A sample that is reactive in both the EIA screening test and the Western blot is presumed [!] to be positive for antibody to HIV-1, indicating infection with this virus except in situations of passively acquired antibody or experimental vaccination…Sensitivity and specificity of the HIV-1 Western Blot Kit was determined in comparative studies with a previously licensed HIV-1 Western blot using EIA repeatedly reactive samples from high AIDS risk and low risk populations respectively [i.e. without a ‘gold standard’ such as virus purification] [Specificity can only be tested with EIA negative specimens, of which there were none].”
Human Immunodeficiency Virus Type 1 (HIV-1) HIV-1 Western Blot Kit. Epitope.
“After blood grouping and cross-match, the HIV negative blood from donor to recipient mice showed bands corresponding to gp120 and gp160 were observed in nine mice. Two mice had both gp120 and gp160 bands and one unidentified peak, two showed only one band gp160 and five had weak gp160 bands the so called indeterminate bands for positive but not complete absence of bands…One would think that if there really were HIV proteins, and that the HIV antibodies were truly specific, then just having one band light up would be proof that HIV is present. But according to experts, that is not the case, you need more than one3. The intriguing thing is, even if one or two bands are not sufficient to diagnose HIV infection, there must still be a reason why they are there. In fact cross-reaction is the explanation given by all HIV experts for “noninfected” Western Blots3. But if one or two bands in the WB can be caused by non-HIV, cross reacting antibodies why cant three or four or five or all of the ten bands be caused by cross reacting non-HIV antibodies. Around the world different combinations of two or three or four bands of the possible ten bands are deemed proof of infection. In Africa you need only two, envelop proteins without gag or pol to prove HIV infection, (WHO Criteria). FDA and Red Cross rules you need three bands. We conclude therefore that the HIV antibody proteins in the Western Blot antibody test are not specific.”
Kabati CIA et al. Testing for HIV Specific Proteins in Otherwise Western Blot Negative Theiller

Albino Mice. TaJONAS.


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