Testing for human immunodeficiency virus.
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Biomedical subjects
Publications and source records attributed to J J Goedert.
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Health care workers are caring for an increasing number of persons infected with human T-cell lymphotropic virus type III (HTLV-III), the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). We studied 361 health care and clinical laboratory personnel from institutions in several metropolitan areas with both high and moderate levels of HTLV-III infection among high-risk group members to evaluate routes of exposure to and seropositivity for HTLV-III. Protection of the privacy of subjects and prospective determination of risk factors were integral components of the study design. Six (26%) of 23 health care workers with recognized risk factors for AIDS had HTLV-III antibodies. Thirty-nine (14%) of 278 workers at one institution as well as a total of five workers from other institutions reported possible percutaneous exposure to HTLV-III, usually injuries with needles that had been used on AIDS patients. There were three HTLV-III seropositive subjects who reported possible parenteral exposure to HTLV-III but no recognized AIDS risk factors. One was a symptomatic female, subject A, and her apparent sources of HTLV-III exposure were two puncture wounds, without injection of blood, made with needles used on AIDS patients. Human T-cell lymphotropic virus type III was cultured from her asymptomatic, seronegative long-term sexual partner, apparently representing female-to-male transmission. For the two other seropositive workers (subjects B and C) with nosocomial parenteral exposure, we could not rule out heterosexual transmission as a possible source of HTLV-III exposure. These latter two cases as well as the identification of seropositive health care providers from known risk groups point to the need for thorough case investigation to identify routes of exposure in health care workers. The risk of nosocomial HTLV-III transmission appears to be low and related to percutaneous exposure. Medical personnel should be trained systematically in the proper techniques and handling of instruments for phlebotomy and similar procedures to decrease occupational exposure to HTLV-III.
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Antibodies to human T-cell lymphotropic virus type III (HTLV-III) were first detected in 1979 in serum samples from 30 known seropositive patients with hemophilia, over half of whom seroconverted in 1981-1982. Lymphadenopathy was present in 70% who were seropositive more than three years, compared with 10% who were seropositive three years or less. T-helper cell counts were low (307 +/- 64 cells/cu mm) in the early seroconverters, and normal in the late seroconverters. T-suppressor cell counts were not related to the year of seroconversion. The long latency period after seroconversion suggests an ongoing indolent process, rather than an acute infection. It remains to be determined whether this is an aberrant part of the immune response initiated by HTLV-III antigens or the result of a chronic active HTLV-III infection.
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The third member of the human T-cell leukemia (lymphotropic) retrovirus family (HTLV-III) is a newly discovered retrovirus that has been closely associated with the acquired immunodeficiency syndrome (AIDS). In our application of an enzyme-linked immunosorbent assay (ELISA) for HTLV-III antibodies, 72 (82%) of 88 patients with AIDS were positive, 14 (16%) were borderline, and two (2%) were negative. In contrast, only 1% of 297 volunteer blood donors were positive, 6% were borderline, and 93% were negative, demonstrating that this ELISA for HTLV-III antibodies is highly specific and sensitive for AIDS (excluding borderline results, 98.6% and 97.3%, respectively). Among persons at high risk for AIDS, 8% had borderline results, with positive and negative results readily distinguished as bimodal distributions that paralleled the temporal and geographic trends in AIDS. None of the 188 laboratory and health care employees working with patients with AIDS or their specimens were positive for HTLV-III antibodies, indicating that current precautions for health care workers appear adequate. This ELISA for HTLV-III antibodies will be a useful screening test among blood donors and populations at risk for AIDS, will aid in the diagnosis of suspected AIDS, and will help in defining the spectrum of diseases that are etiologically related to HTLV-III.
Human T-lymphotropic virus type III (HTLV-III) is a recently discovered retrovirus with tropism and cytotoxicity for the OKT4+ lymphocytes that are depleted in the acquired immune deficiency syndrome (AIDS). In addition to the frequent detection of HTLV-III in patients with AIDS and related syndromes, seroepidemiological studies have shown that HTLV-III can be transmitted by sexual contact and blood transfusion in a manner identical to the putative AIDS agent. Analyses of stored sera have revealed that HTLV-III antibodies appeared in high-risk groups some two years before the disease outbreak, which corresponds to the apparent incubation period in patients with transfusion-associated AIDS. The risk of developing AIDS is clearly associated with HTLV-III seropositivity and may be as high as 20% within three years. Strong evidence that HTLV-III is the AIDS agent mandates aggressive efforts to minimize further sexual, maternal-fetal, and blood-borne transmission of this virus while pursuing vaccine development and antiretroviral therapies.
In June 1982, sexual and other behavioral patterns were examined in 245 homosexual men in relationship to T-lymphocyte phenotypes that are characteristic of the acquired immunodeficiency syndrome (AIDS). Mean helper T-cell counts in New York City (579 +/- 32 cells/mm3) and Washington, DC, homosexual men with sexual contacts in areas at high risk (endemic) for AIDS (567 +/- 24 cells/mm3) were significantly lower than in Washington, DC, residents without such contacts (672 +/- 36 cells/mm3, p = 0.04 by analysis of variance). Helper T-cell counts in the Washington men were inversely correlated with a greater number of endemic-area homosexual contacts (p = 0.005), even after adjustment for multiple confounding variables (p = 0.02). The 31 Washington men with more than 15 endemic-area partners had a mean helper T-cell count of 517 +/- 44 cells/mm3, and 12 of those 31 men had helper T-cell counts less than 400 cells/mm3. AIDS patients are known to have a marked reduction in the number and function of helper T-lymphocytes. The data suggest that deficits of helper T lymphocytes can be acquired by homosexual contact with men in cities where AIDS is common. This supports the hypotheses that low helper T-cell counts may be caused by a sexually transmissible agent and that frequent homosexual exposure to residents of high-risk areas for AIDS may be an important means of spread of this agent.
In June 1982, the sexual practices of 245 homosexual male outpatients of private physicians were evaluated in relationship to decreased numbers of helper T lymphocytes, an abnormality that is characteristic of the acquired immunodeficiency syndrome (AIDS). Three risk groups were defined a priori--85 high-risk men from central Manhattan ("New York"), 96 intermediate-risk men from Washington, DC, with AIDS-area homosexual contacts ("Washington-exposed"), and 64 low-risk Washington, DC, men without such contacts ("Washington-unexposed"). An increasing number of homosexual partners was correlated with decreasing helper T-cell counts (R = -0.29, p = 0.009) and decreasing helper:suppressor T-cell ratios (R = -0.32, p = 0.005) in the entire study group combined and in New York subjects separately. Suppressor T-cell counts were unrelated to the number of partners in all three groups. Increasingly frequent receptive anal intercourse correlated with decreasing helper T-cell counts most clearly in the New York City group (R = -0.23, p = 0.04), somewhat less so in the Washington-exposed group (R = -0.18, p = 0.07), and not at all in the Washington-unexposed group (R = -0.09, p = 0.48). This association persisted in the New York and Washington-exposed groups after adjusting for seven other sexual practices, the number of homosexual partners, and five other potentially confounding variables. A transmissible agent associated with receptive anal intercourse best explains these data. The cause of these low helper T-cell counts may also be the cause of AIDS.
The discovery of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) has opened a window to the understanding of the spectrum of the acquired immunodeficiency syndrome (AIDS) and related clinical syndromes. Analysis of risk factors for seropositivity has shown that HTLV-III is transmitted most efficiently via routes that involve close personal contact or parenteral exposure. Longitudinal studies have shown that HTLV-III infection has a long latent period. The prevalence of AIDS in different geographic areas and among different risk groups appears to depend in part on duration of exposure. Co-factors for AIDS outcome such as manner and route of exposure, underlying immune status, and host susceptibility are also likely to play a role in risk.
The third member of the family of T cell leukemia viruses (HTLV III) has been proposed as the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia, particularly those with factor VIII deficiency who receive commercial clotting factor concentrates. In a prevalence survey conducted between September 1982 and April 1984, initial serum samples from 74% of hemophiliacs who had ever been treated with commercial factor VIII concentrate, 90% of those frequently treated with factor VIII concentrate, and 50% of those treated with both factor VIII and factor IX concentrates had antibodies reactive against antigens of HTLV III, compared with none of the hemophiliacs treated only with factor IX concentrate or volunteer donor plasma or cryoprecipitate. Two of the seropositive patients have developed AIDS-related illnesses, and a third patient died of bacterial pneumonia. One initially seronegative patient developed antibodies against HTLV III during the study and is currently well. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV III, suggesting that factor VIII concentrate may transmit the p24 and p41 antigens of HTLV III. However, the presence of infectious retroviruses in clotting factor concentrates and the effectiveness of screening and viral neutralization procedures remain to be determined.
The discovery of HTLV-I opened the way for the subsequent recognition of other human retroviruses. HTLV-I is linked to an aggressive T-cell cancer. The availability of a marker for the AIDS agent, HTLV-III, has substantially enhanced our ability to define the nature of the AIDS epidemic, its clinical and subclinical manifestations, and the spectrum of disease outcomes associated with this exposure. Of particular interest is the fact that there is substantial risk for AIDS and AIDS-related outcomes in virally infected individuals as detected by antibody positivity. The preliminary data from these well defined cohorts provide a basis for estimating the enormity of the AIDS epidemic as it is starting to emerge and provide an opportunity for the forward thinking health strategies necessary for dealing with a pandemic of such proportions.
Recent case reports have suggested that the acquired immunodeficiency syndrome (AIDS) may be associated with cancers other than Kaposi's sarcoma (KS). We have used the population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program to examine these relationships on a statistical basis by comparing the morbidity odds ratio (OR) and 95% confidence interval (CI) for specific cancer sites in pre- and post-AIDS time periods. Among never-married 20- to 49-year-old men, a surrogate group representing homosexual men, significant increases in the morbidity OR's for KS between 1973-80 and 1981-82 were apparent in the San Francisco standard metropolitan statistical area (OR: 51.8; CI: 18.6-143.6) and in other areas covered by the SEER Program (OR: 18.6; CI: 2.2-154.5). Furthermore, a significant increase was found in the morbidity OR for Burkitt-like lymphoma in the San Francisco metropolitan area (OR: 9.1; CI: 1.8-45.6). In San Francisco County (which includes the City of San Francisco), there was a 2,043-fold increase in the morbidity OR for KS and a fivefold increase for Burkitt-like lymphomas, but there were no significant changes for other cancers between 1973-79 and 1982. Similarly, no significant changes in morbidity OR's were observed for other cancers in the remaining SEER registries. These findings provided statistical support for the excess risk of Burkitt-like lymphoma in a group at risk of AIDS.
77 Scottish haemophiliacs and 22 Danish haemophiliacs were serologically tested for antibodies to human T-cell leukaemia virus III (HTLV-III). Since 1979 the Scottish patients had been treated largely with factor VIII concentrate produced in Scotland, whereas all but 2 of the Danish patients had received both locally prepared concentrate and commercial concentrate made from US donor material. 15.6% of Scottish and 59.1% of Danish haemophiliacs were antibody positive (p less than 0.001). None of 11 haemophiliacs not treated in the period 1979-84 was seropositive. 2 (6.7%) of 30 subjects who had been treated with locally produced concentrate only were antibody positive, compared with 23 (39.7%) of 58 subjects who had been treated with commercial concentrate. Among 52 users of both commercially and locally produced factor VIII concentrate, seropositivity was directly correlated with the consumption of commercial concentrate (p less than 0.001) but not locally produced material. These data indicate that European haemophiliacs were exposed to HTLV-III via some factor VIII concentrates obtained from the USA.
A cohort of homosexual men at high risk of the acquired immunodeficiency syndrome (AIDS) was monitored to examine the relation between lifestyle, clinical conditions, T-lymphocyte subsets, and antibody to the AIDS-associated human retrovirus, human T-cell leukaemia virus III (HTLV-III). HTLV-III antibodies were present in 35 (53%) of the 66 subjects tested in June, 1982. 4 of the seronegative subjects had HTLV-III antibodies when re-tested one year later, a seroconversion rate of 1.2% per month. In the HTLV-III seropositive subjects, AIDS developed at a rate of 6.9% per year (minimum incidence of AIDS = 4.6% per year) and other clinical signs of immunodeficiency (lesser AIDS) at 13.1% per year. All 6 of the AIDS cases and at least 8 of the 10 lesser AIDS cases had detectable HTLV-III antibodies 1 week to 21 months before diagnosis. Of 24 other subjects with stable lymphadenopathy, 19 (79%) had or acquired HTLV-III antibodies. Lower helper T-cell counts were very closely related to HTLV-III seropositivity (r = -0.53, p = 0.0001), even in the 26 healthy subjects with no clinical abnormalities (r = -0.37, p = 0.07). In both univariate and multivariate analyses, the lifestyle risk factors for HTLV-III seropositivity were large number of homosexual partners (p less than or equal to 0.03) and receptive anal intercourse (p less than or equal to 0.03), with an apparent synergistic interaction between these two activities (chi 2 = 8.71, p = 0.003). These data suggest that frequent receptive anal intercourse with many homosexual partners predisposes to HTLV-III infection with the consequent emergence of lymphadenopathy and the various manifestations of lesser and fully fledged AIDS.
To investigate risk factors for immunologic abnormalities among homosexual men, T-lymphocyte helper/suppressor (OKT4/OKT8) ratios were determined in 78 healthy Danish homosexual men. Ratios in 26 men (33%) were low (less than 1.00). Visiting the United States in 1980 to 1981 was a strong (7.7-fold) risk factor for having a ratio less than 1.00. Among nine travelers who visited only once, the risk of having a low ratio increased significantly if the visit had occurred in 1981. A risk of similar magnitude (6.9-fold) was found among the three men who had not been to the United States but who reported homosexual contact with a Danish man who became ill with Kaposi's sarcoma. Risk of low ratios did not correlate with age or years of homosexual activity. Promiscuity was not a significant risk factor, but these men generally had fewer sex partners than that which has been reported from the United States. Neither nitrite inhalant use nor cytomegalovirus antibody (prevalence or titer) was associated with low ratios. These data support the hypothesis that a transmissible biologic agent may be etiologically responsible for the low helper/suppressor ratios in homosexual men.