Stanley H. Weiss

DETERMINANTS OF RETROVIRUS (HTLV-III) ANTIBODY AND IMMUNODEFICIENCY CONDITIONS IN HOMOSEXUAL MEN

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.

Screening test for HTLV-III (AIDS agent) antibodies: specificity, sensitivity, and applications.

The third member of the human T-cell leukemia (lymphotrophic) 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. ( JAMA 1985;253:221-225)

The AIDS Epidemic

This article reviews the magnitude of human T-lymphotropic virus type III (HTLV-III) exposure, the outcome of such exposure, the economic burden of HTLV-III-related disease, and the social, ethical and public implications of the acquired immunodeficiency syndrome (AIDS) epidemic. The ELISA serum antibody test for HTLV-III is useful for diagnostic purposes, but does not indicate whether the person currently harbors the virus. Additional studies are needed to demonstrate that there are not antibodies to other viruses that cross-react in the test. Seropositivity from lymphadenopathy-associated virus (LAV) rose from under 10% in 1978 to 49% in 1984 among homosexual men attending a Colorado clinic for sexually transmitted diseases. In San Francisco, the prevalence of HTLV-III antibodies among homosexual men attending another such clinic reached 65% in 1984. Parenteral drug users have demonstrated similar increases in seropositity rates. The total number of persons in the US who are positive for HTLV_III antibodies is estimated to be at least 400,000 persons. Initial study results suggest that 4-19% of these seropositive individuals develop full-blown AIDS in 1-5 years. 40,000 new cases of AIDS are expected in the next 2 years. The AIDS epidemic has severely stressed the US health care system in terrms of its financial costs, use of resources, and effect on medical personnel. It is not unreasonable to estimate that AIDS will cost US society over half a billion dollars during the next calendar year. The grat social and economic burden associated with AIDS, and the effects of a positive ELISA test upon those tested, create a multitude of concerns. There is a need for a national coordinated health program on AIDS, as well as for special measures such as a national catastrophic fund for HTLV-III-related disease. Finally, the threasts to confidentiality posed by licensure of the HTLV-III antibody test must be recongnized.

Epidemiology of human T-lymphotropic virus type III and the risk of the acquired immunodeficiency syndrome.

Abstract 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 immunodeficien...

Possible Female-to-Female Transmission of Human Immunodeficiency Virus

Excerpt To the editor: A case of the acquired immunodeficiency syndrome (AIDS) in a lesbian without any recognized risk factors was reported in 1984 (1). Consistent with that observation, we report...

Herpes simplex type II and Mycoplasma genitalium as risk factors for heterosexual HIV transmission: Report from the heterosexual hiv transmission study

OBJECTIVES Two hundred twenty-four human immunodeficiency virus (HIV) discordant couples (one HIV negative, one HIV positive) were compared with 78 seroconcordant heterosexually infected couples with HIV with regard to sexually transmitted diseases. METHODS Serologic testing and cultures were used to determine exposure of participants to sexually transmitted pathogens. These data were compared with HIV concordance of partners to investigate possible risk factors for HIV transmission. RESULTS Syphilis, chlamydia, and hepatitis B virus (HBV) serologies did not distinguish between concordant and discordant couples nor did cultures for Neisseria gonorrhoeae and Trichomonas or Chlamydia enzyme immunoassay (EIA). Risk of transmission increased with positive serologies for herpes simplex virus (HSV)-2 (P = 0.002), cytomegalovirus (CMV) (P = 0.04), and Mycoplasma genitalium (P = 0.01), but not with Mycoplasma fermentans or Mycoplasma penetrans. Cytomegalovirus was not a significant risk factor when controlled for HSV-2 status. Examination by partner status showed increased risk of concordance with: HSV-2 positive serology in both partners (odds ratio [OR] = 3.14; confidence interval [CI] = 1.62-6.09; P = 0.007); HSV-2 in female secondary partner (OR = 2.10; CI = 1.12-3.93; P = 0.02) or the male primary partner (OR = 2.15; CI = 1.15-4.02; P = 0.017); M. genitalium antibody in both partners (OR = 3.44; CI = 1.68-7.04; P < 0.001); M. genitalium antibody in the primary male partner (OR = 2.51, CI = 1. 27-4.91; P = 0.008) and M. genitalium antibody in the secondary female partner (OR = 2.52; CI = 1.21-5.23; P = 0.01). CONCLUSIONS These data support the role of HSV-2 in transmission of HIV and, for the first time, suggest a role for M. genitalium as an independent risk factor.

Seroprevalence of Toxoplasma gondii in Pregnant Women and Cats in Grenada, West Indies

Prevalence of antibodies against Toxoplasma gondii was studied in 534 pregnant women and 40 domestic cats in Grenada, West Indies. Antibodies (IgG) for T. gondii were sought in human sera by an enzyme-linked immunosorbent assay and in cat sera by using the modified agglutination test (MAT). Antibodies were found in 57 % of pregnant women. Seroprevalence increased with age; 51% of 15- to 19-yr-old women (100 total) had antibodies versus 60% of 20- to 24-yr-old women (127 total). Antibodies to T. gondii (MAT, 1:25 serum dilution) were found in 35% of cats; titers were 1:25 in 7 cats, 1:50 in 4 cats, and 1:500 in 3 cats. Epidemiological data suggested that the ingestion of food or water contaminated with oocysts was an important mode of transmission of T. gondii to women.

Spontaneous lymphocyte proliferation in HTLV-II infection

We measured lymphocyte proliferation in the absence of antigenic stimulation in 45 HTLV-II infected, 9 HTLV-I infected, and 19 HTLV-I seronegative intravenous drug users (IVDU). Lymphocyte proliferation was higher in IVDUs infected with HTLV-II than in seronegative IVDUs but lower than among those infected with HTLV-I. Higher rates of proliferation were also associated with needle sharing, CD4+ and IL2R+ lymphocyte counts, and HTLV-I antibody titres.

The future of epidemiology.

In this article, the authors discuss current challenges and opportunities in epidemiology that will affect the fields future. Epidemiology is commonly considered the methodologic backbone for the fields of public health and outcomes research because its practitioners describe patterns of disease occurrence, identify risk factors and etiologic determinants, and demonstrate the usefulness of interventions. Like most aspects of science, epidemiology is in rapid flux. Several factors that are influencing and will continue to influence epidemiology and the health of the public include factors fundamental to framing the discipline of epidemiology (i.e., its means of communication, its methodologies, its access to data, its values, its population perspective), factors relating to scientific advances (e.g., genomics, comparative effectiveness in therapeutics), and factors shaping human health (e.g., increasing globalism, the environment, disease and lifestyle, demographics, infectious disease).

Development of a multiplex PCR assay for the simultaneous detection and discrimination of HIV-1, HIV-2, HTLV-I and HTLV-II

BACKGROUND Multiplex polymerase chain reaction (PCR) has been established as a general technique for the simultaneous amplification of different target sequences. Uses of multiplex include pathogens identification, linkage analysis and genetic disease diagnosis. The high sensitivity of PCR may produce false-positive results due to contamination with previously amplified material. OBJECTIVES To develop a multiplex PCR technique that can simultaneously detect and discriminate human immunodeficiency virus types 1 and 2 (HIV-1/2) and human T-lymphotropic virus types 1 and 2 (HTLV-I/II) proviral sequences. Such a method should incorporate a system that prevents the occurrence of false-positive results. STUDY DESIGN Combinations of four primer pairs, one for each retrovirus, were assayed in order to determine the combination of oligonucleotides as well as the PCR conditions that yield the most specific and sensitive coamplification of proviral sequences. To prevent contamination with DNA from previous PCR amplifications, the uracil N-glycosylase (UNG) system was incorporated into the coamplification format. RESULTS A combination of primer pairs from the gag region of HIV-1, env of HIV-2, pol of HTLV-I and tax of HTLV-II yielded specific and sensitive coamplification of proviral sequences. The UNG system was incorporated and shown to be efficient in the degradation of contaminating DNA. In the evaluation of a serologically well established panel of singly and dually infected individuals, the assay detected 20/22 HIV-1, 8/10 HIV-2, 8/8 HTLV-I and 8/8 HTLV-II infections.