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
Email: David.Crowe@aras.ab.ca

Roger Swan, Treasurer
Box 61037, Kensington Postal Outlet
Calgary, Alberta T2N 4S6
Canada
Office
Phone: +1-403-220-0129
Email: aras@aras.ab.ca
Web: noaids.ca

Referenced Quotes about HIV/AIDS Tests and Measurements

Antigen Tests (p24)

Antigen tests are the opposite of antibody tests. An antibody is a protein produced by an immune system in response to a foreign protein (the antigen), such as a virus coat. Antigen tests (usually with the p24/p25 protein) have not been spectacularly successful, because many people who are antibody positive do not have HIV antigen. One would think that this would mean that these people have only been exposed to HIV (hence the antibodies) but not infected (hence no antigens). Yet, in the topsy-turvy world of AIDS, the opposite interpretation is taken.

“Virus levels in the peripheral blood can be quantitated by measurement of the HIV p24 antigen in serum, by quantitative culture of HIV from plasma, or by direct measurement of viral RNA in plasma using nucleic acid amplification or signal amplification technologies. p24 antigen is the principal core protein of HIV and is found in serum either free or bound by anti-p24 antibody. Free p24 antigen can be measured with commercially available enzyme immunoassays (EIA), although the usefulness of p24 antigen as a marker of viral load is limited since the antigen is detectable in only 20% of asymptomatic patients and 40-50% of symptomatic patients…the viral protein remains undetectable in most asymptomatic patients”
“Among 37,164,054 units [of donated blood] screened, 12 were confirmed to be positive for HIV-1 RNA…only 2 of which were detected by HIV-1 p24 antigen testing”
Stramer SL et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med. 2004 Aug 19;351(8):760-8.
“Experience has shown that HIV culture and ‘standalone’ tests for p24 antigen are of limited diagnostic value. They may be insensitive and/or non-specific, and they are expensive compared with the standard serological screening tests…When testing for p24 Ag it must be remembered that it, too, is prone to false positivity, which must be ruled out by a neutralisation test.”
Parry JV et al. Towards error-free HIV diagnosis: guidelines on laboratory practice. Commun Dis Public Health. 2003 Dec;6(4):334-50.
http://www.hpa.org.uk/cdph/issues/CDPHvol6/No4/6_4guideline1.pdf
“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 p24 antigen test had specificity of 99.5%…[but] a lower sensitivity than HIV-1 RNA testing: 79%”
Hecht FM et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS. 2002 May 24;16(8):1119-29.
“These workers conclude that, in analogy to previous findings with HIV p24 gag reactivity in systemic lupus erythematosus (SLE) and Sjögren’s syndrome, the presence of antibodies reacting with denatured HIAP antigens indicates retroviral infection. However, they do not mention that studies with native viral HIV p24 gag-protein did not show antibody reactivity to these patients with Sjögren’s syndrome, not even in the presence of antibodies reacting with HIV p24 gag in an immunoblot assay.2 Such a pattern of reactivity is not expected when specific antibodies are the result of infection with this retroviral agent but is much more suggestive of crossreactivity of (auto)antibodies with an epitope only present under denaturing (immunoblot) conditions. The latter explanation of course implies that there is no evidence of retroviral infection in PBC. Only demonstration of the actual retroviral agent in liver biopsy specimens of patients would really support infection.”
Meilof JF, Smeenk RJ. Detection of retroviral antibodies in primary biliary cirrhosis. Lancet. 1998 Aug 29;352(9129):739-40.
“We did western blot tests for HIV-1…on serum samples from 77 patients with primary biliary cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic lupus erythematosus, and 25 healthy volunteers. HIV-1 p24 gag seroreactivity was found in 27 (35%) of 77 patients with primary biliary cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of 28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with either primary sclerosing cholangitis or biliary atresia, compared with only one (4%) of 24 patients with alcohol-related liver disease or alpha1-antitrypsin-deficiency liver disease, and only one (4%) of 25 healthy volunteers…The HIV-1…antibody reactivity found in patients with primary biliary cirrhosis and other biliary disorders may be attributable either to an autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterised viral proteins that share antigenic determinants with these retroviruses. [Even though these are antibody tests, and this one antibody reaction does not result in an HIV diagnosis, this indicates that the protein known as p24 is not unique to HIV]
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.
“The sensitivity of p24 antigenemia was 59%”
Delamare C et al. HIV-1 RNA detection in plasma for the diagnosis of infection in neonates. The French Pediatric HIV Infection Study Group. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Jun 1;15(2):121-5.
“HIV-1 p24 antigen is present only transiently prior to seroconversion and later can be complexed by specific antibodies. HIV-1 p24 antigen testing should not be used in lieu of HIV-1 antibody testing as a screen for HIV-1 infection.”
Antibody to Human Immunodeficiency Virus type 1; HIVAG-1 Monoclonal. Abbott Laboratories. 1996 Apr
http://davidcrowe.ca/SciHealthEnv/papers/2402-AbbottAntigen.pdf
“Routine testing for p24 antigen in settings other than blood and plasma centers as a method for diagnosing HIV infection is discouraged because the estimated average time from detection of p24 antigen to detection of HIV antibody is 6 days and not all recently infected persons have detectable levels of p24 antigen…p24-antigen tests alone should not be used for diagnosing HIV infection.”
US Public Health Service guidelines for testing and counseling blood and plasma donors for Human Immunodeficiency Virus Type 1 antigen. MMWR. 1996 Mar 1;45(RR-2).
“None of the 50 seronegative partners had p24 antigen in their serum. 22 (44%) of the seropositive partners had detectable p24 antigen.”
MacGregor RR et al. Failure of culture and polymerase chain reaction to detect human immunodeficiency virus (HIV) in seronegative steady sexual partners of HIV-infected individuals. Clin Infect Dis. 1995 Jul;21(1):122-7.
“HTLV-III [HIV] has been shown to be antigenically related to HTLV-I and HTLV-II by demonstrating cross-reactivity with antibodies to HTLV-I and HTLV-II core proteins, p24 and p19.”
Chang NT et al. Cloning and Expression of HTLV-III DNA. USPTO. 1995 Jun 5;6,001,977.
“p24 antigen was detected in 6 patients of group P [positive] and 2 patients of group N [HIV-negative].”
Urano H et al. HIV isolation may not correlate with clinical state or immunological function of respective HIV infected patients. Int Conf AIDS. 1994 Aug;10(2):255.
“TABLE 1. Comparison of the estimated mean number of RNA copies per milliliter of plasma with the mean titer of virus in plasma and the p24 antigen level in symptomatic and asymptomatic patients [for symptomatic, HIV-positive patients 100% had detectable RNA ‘viral load’ but only 34/41 of these had positive virus cultures and only 22/35 had p24 antigen detectable] [for asymptomatic HIV-positive patients 29/39 had ‘viral load’ detectable at low levels but only 5/39 had positive virus cultures and 5/38 detectable p24 antigen]
Van Kerckhoven I et al. Quantification of human immunodeficiency virus in plasma by RNA PCR, viral culture, and p24 antigen detection. J Clin Microbiol. 1994 Jul;32(7):1669-73.
“At the time of delivery, HIV-1 p24 antigen was detected in serum from 16 of 108 [HIV+] women (15%)”
Blanche S et al. Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery. N Engl J Med. 1994 Feb 3;330(5):308-12.
“In 81 (72%) of [HIV-]positive subjects p24 antigenaemia was found in subsequent checks for a median duration of 20 months. p24 antigenaemia was not associated with any clinical pattern.”
Italian Register for HIV INfection in Children. Features of children perinatally infected with HIV-1 surviving longer than 5 years. Lancet. 1994 Jan 22;343(8891):191-5.
“There was no correlation between HIV-1 p24 antigen assay and syncytium [a special type of large cell with several nucleuses that is found only in cell cultures] formation assay results.”
Bagasra O, Pomerantz RJ. Human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells in the presence of cocaine. J Infect Dis. 1993 Dec;168(5):1157-64.
[The abstract states, without qualification, that] In the two didanosine groups, there were improvements in the number of CD4 cells and in p24 antigen levels, as compared with the zidovudine [AZT] group…[but later the paper states] Among the subjects initially positive for serum p24 antigen [fewer than half], significantly higher proportions of those in the 750-mg and 500-mg didanosine groups had p24 antigen levels that declined by at least 50%.”
Kahn JO et al. A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group. N Engl J Med. 1992 Aug 27;327(9):581-7.
“Of 61 infected children tested 46 (75%) had at least one positive test for antigen”
Kind C et al. Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study. Eur J Pediatr. 1992;151:442-8.
“Cryostat sections of human normal term placentae were …examined for HIV protein antigens gp120, p17, p24, and gp41. No evidence for gp41 was found. Antigens gp120 and p17 were identified in normal chorionic villi in vimentin-positive fibroblast-like cells and in endothelium, respectively. Antigen p24 was localized to HLA-DR positive cells that morphologically resembled macrophages in areas of villitis. [i.e. HIV proteins are found in uninfected human placentas!!]
Faulk WP, Labarrere CA. HIV proteins in normal human placentae. American Journal of Reproductive Immunology. 1991;25:99-104.
“HIV-1 p24 is the HIV-1 protein most prone to "false-positive" reactions”
Ng V. Serological diagnosis with recombinant peptides/proteins. Clin Chem. 1991;37(10):1667-8.
“there were 16 sera from 30 viraemic patients which did not have detectable p24 antigen”
Semple M et al. Direct measurement of viraemia in patients infected with HIV-1 and its relationship to disease progression and zidovudine therapy. J Med Virol. 1991;35(1):38-45.
“there were 16 sera from 30 viraemic patients which did not have detectable p24 antigen (<5 pg/ml, Fig. 2). As a consequence, p24 antigen concentration and HIV-1 RNA did not correlate well.”
Semple M et al. Direct measurement of viraemia in patients infected with HIV-1 and its relationship to disease progression and zidovudine therapy. J Med Virol. 1991;35(1):38-45.
“The p24 antigen was negative in seronegative persons at high and low risk but positive in 6 of 92 HIV-1-seropositive individuals [who were also negative by DNA PCR]
Lefrere JJ et al. No evidence of frequent HIV-1 infection in seronegative at-risk individuals. Transfusion. 1991;31(3):205-11.
“Baseline serum p24 antigen levels were measured in 71 patients. At entry, 37 (52%) were positive for the antigen...and 34 (48%) were negative [yet all were positive for HIV antibodies]
McKinney RE et al. A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. N Engl J Med. 1991 Apr 11;324(15):1018-25.
“of the children who got AIDS, 10 out of 13 (77%) had at least one position antigen test in the pre-AIDS period, compared with 20 out of 27 (74%) of antibody-positive infected children who did not get AIDS and who were followed for over 18 months”
European Collaborative Study. Children born to women with HIV-1 infection: natural history and risk of transmission. Lancet. 1991 Feb 2;337(8736):253-60.
“Our analysis of the group of men who had only single HIV-1 Ag+ determinations or transient antigenemia showed no evidence of a different rate of progression to AIDS compared to that in the men with persistent antigenemia.”
MacDonell KB et al. Predicting progression to AIDS: combined usefulness of CD4 lymphocyte counts and p24 antigenemia. Am J Med. 1990 Dec;89(6):706-12.
“Of 515,494 donor samples tested for p24 antigen at the blood centers, 0.43% were initially reactive. Of these samples, only 18% were repeatedly reactive…Among the repeatedly reactive samples…retested at the central laboratory, 58% (representing 0.05% of the total population) were verified as repeatedly reactive.”
Alter HJ et al. Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors--an assessment of the efficacy of testing in donor screening. The HIV-Antigen Study Group. N Engl J Med. 1990 Nov 8;323(19):1312-7.
“205 subjects (of 406 tested (50%)) had detectable serum levels of HIV antigen before treatment [i.e. 50% were negative for HIV antigen, although positive for HIV antibodies]
Fischl MA et al. A randomized controlled trial of a reduced daily dose of Zidovudine in patients with the Acquired Immunodeficiency Syndrome. N Engl J Med. 1990;323(15):1009-14.
“lower levels of HIV p24 antigen…[was] significantly correlated with the risk of progression to AIDS”
Volberding PA et al. Zidovudine in asymptomatic human immunodeficiency virus infection: a controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N Engl J Med. 1990 Apr 5;322(14):941-9.
“In only 45 percent of persons from whom we isolated plasma-associated HIV [by co-culture techniques] was p24 antigen detected in plasma or serum”
Coombs RW et al. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989 Dec 14;321(24):1626-31.
“no infants, including those who later had AIDS, were positive for serum antigen [p24] during the neonatal period”
Rogers MF et al. Use of the polymerase chain reaction for early detection of the proviral sequences of human immunodeficiency virus in infants born to seropositive mothers. N Engl J Med. 1989 Jun 22;320(25):1649-54.
[4 frozen blood samples from DNCB-anergic seroconverters] were negative for p24 antigen”
Marion SA et al. Evidence that prior immune dysfunction predisposes to Human Immunodeficiency Virus infection in homosexual men. J Acquir Immune Defic Syndr. 1989;2(2):178-86.
“In comparison with antibody testing, antigen testing will only detect approximately 50% of AIDS, 30% of ARC [AIDS Related Complex] and 10% of asymptomatic HIV infections”
HIVAG-1; Antibody to Human Immunodeficiency Virus Type 1. Abbott Laboratories. 1989
http://davidcrowe.ca/SciHealthEnv/papers/2401-AbbottAntibody.pdf
“The serum antigen assay [probably p24], carried out twice on each sample, was positive for 6 of the 21 (29%) samples from seropositive subjects…13 (76%) of the seventeeen HIV-DNA-positive subjects were negative for serum antigen”
Hart C et al. Direct detection of HIV RNA expression in seropositive subjects. Lancet. 1988 Sep 10;2:596-9.
“The HIV antigen [p24] test is probably not an adequate measure of infectivity…even though positive results are suggestive of high titres of circulating virus”
Mortimer PP. The AIDS virus and the HIV test. Med Int. 1988;56:2334-9.
“The weak correlation between [erythrocyte sedimentation counts, which was correlated with progression to AIDS] and positive HIV antigenemia [positive p24 antigen test] is of interest”
Lefrere JJ et al. Sedimentation rate as a predictive marker in HIV infection. AIDS. 1988 Feb;2(1):63-4.
“In a prospective study conducted from September 1993 through September 1995, a total of 305,989 donations were tested for p24 antigen; [1,348 were positive on the first p24 test, 144 of those were positive on at least 1 of 2 subsequent p24 tests and] 3 donors had both repeatedly reactive p24-antigen EIA screening-test results and positive neutralization results (two of whom were also HIV-antibody positive), and 223 donors had repeatedly reactive p24-antigen EIA screening-test results and negative neutralization results.”
CDC. Public Health Service Guidelines for Counseling and Antibody Testing to Prevent HIV Infection and AIDS. MMWR. 1987 Aug 14;36(31):509-15.
http://www.cdc.gov/mmwr/PDF/RR/RR4502.pdf
“Whether the production of HIV antigen [p24 or p25] accurately reflects complete viral replication with the production of infectious virions is still to be investigated”
Lange JMA et al. Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS. BMJ (Clin Res Ed). 1986;293:1459-62.
“Extensive accumulation of p24 and p41 occurred in the [HIV] virus preparation. Protein stains show that these molecules are the major components of the virus preparation. P24 and p41 may therefore be considered viral structural proteins [What? Just because there’s more of it, but no proof that it actually came from virus particles?]
Schüpbach J et al. Serological Analysis of a Subgroup of Human T-Lymphotropic Retroviruses (HTLV-III) Associated with AIDS. Science. 1984 May 4;224:503-505.

Feedback

We appreciate your comments, feedback, questions and suggestions for improvements to this site. Click here to send us a message.

© Copyright January 21, 2013: Alberta Reappraising AIDS Society