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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.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. 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. 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. US Patent Office. 1999 Dec 14;6,001,977. 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. 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. 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. 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 theres 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. | ||||||||||||||
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