Three-year incidence of AIDS in five cohorts of HTLV-III-infected risk group members.

The incidence of the acquired immune deficiency syndrome (AIDS) among persons infected with human T-lymphotropic virus type III (HTLV-III) was evaluated prospectively among 725 persons who were at high risk of AIDS and had enrolled before October 1982 in cohort studies of homosexual men, parenteral drug users, and hemophiliacs. A total of 276 (38.1 percent) of the subjects were either HTLV-III seropositive at enrollment or developed HTLV-III antibodies subsequently. AIDS had developed in 28 (10.1 percent) of the seropositive subjects before August 1985. By actuarial survival calculations, the 3-year incidence of AIDS among all HTLV-III seropositive subjects was 34.2 percent in the cohort of homosexual men in Manhattan, New York, and 14.9 percent (range 8.0 to 17.2 percent) in the four other cohorts. Out of 117 subjects followed for a mean of 31 months after documented seroconversion, five (all hemophiliacs) developed AIDS 28 to 62 months after the estimated date of seroconversion, supporting the hypothesis that there is a long latency between acquisition of viral infection and the development of clinical AIDS. This long latency could account for the significantly higher AIDS incidence in the New York cohort compared with other cohorts if the virus entered the New York homosexual population before it entered the populations from which the other cohorts were drawn. However, risk of AIDS development in different populations may also depend on the presence of as yet unidentified cofactors.

Effect of knowledge of human immunodeficiency virus infection status on sexual activity among homosexual men.

One hundred thirty-four homosexual men from a prospective cohort study of AIDS risk from New York City and Washington D.C. and 139 homosexual men from a similar cohort in Copenhagen and Aarhus, Denmark were questioned regarding their sexual practices and knowledge of their human immunodeficiency virus (HIV) status over the previous 12 months. Seventy percent of Danish men and 63% of U.S. men participated in anal intercourse during the previous 12 months. Knowledge of one's own HIV status by itself did not have any significant effect on participation in anal intercourse, partner number, or condom use. Only 23% of U.S. men and 24% of Danish men always asked potential partners about their HIV status. However, men who did ask were very unlikely to choose a partner of opposite HIV status (p less than 0.006). Danish men were more likely to practice anal intercourse without a condom than were the U.S. men (p less than 0.0001); however, Danes were more likely to be in a concordant monogamous relationship than were the U.S. men (p less than 0.001). Fourteen percent of U.S. men and 21% of Danish men were not aware of their own HIV status and 52% of the U.S. cohort and 31% of the Danes had anal intercourse with a man whose status was unknown to them. Overall, only 32% of American and 53% of Danish homosexual men were practicing completely safe sex. We suggest that education to promote the need for awareness of one's own and one's partner's HIV status should be stressed.

Cigarette smoking: a modifier of human immunodeficiency virus type 1 infection?

Two hundred and two homosexual men enrolled in a prospective cohort study of AIDS risk were assessed for differences in the occurrence and progression of human immunodeficiency virus type 1 (HIV-1) infection with respect to cigarette smoking. Among subjects who were initially seronegative, smokers were more likely than nonsmokers to become HIV-1 seropositive (p = 0.03). After seroconversion, serum beta 2-microglobulin and CD4+ lymphocyte levels were elevated in cigarette smokers relative to nonsmokers (p = 0.02 for both comparisons), but both of these differences disappeared within 2 years. There was no detectable difference in the risk of AIDS or Pneumocystis carinii pneumonia with respect to smoking. Our data suggest that cigarette smoking may alter the immune response to HIV-1 infection, but it appears to have no marked effect on clinical outcome. They also suggest that cigarette smoking may be a surrogate marker for continued high-risk sexual behavior in homosexual men.

Interaction of human immunodeficiency and papilloma viruses: association with anal epithelial abnormality in homosexual men.

During the 7th annual follow-up of our cohort of homosexual men in 1989, we tested the hypotheses that infection with human immunodeficiency virus (HIV) may enhance the expression of human papilloma virus (HPV) and that the development of anal epithelial abnormality is related to a biologic interaction between these two viruses. Overall, 41 (39%) of the 105 men had anal swabs positive for one or more genotypes of HPV 6/11, 16/18 or 31/33/35. Twenty-three (53%) of the 43 HIV-positive subjects harbored HPV compared to 18 (29%) of the 64 HIV-negative subjects (p = 0.012), including higher prevalence rates for HPV genotypes 16/18 (p = 0.01), 6/11 (p = 0.007), and 31/33/35 (p = 0.07). Multivariate logistic regression analysis of the HIV-positive subjects showed low CD4+ cell counts to be an independent risk factor for detection of HPV (p = 0.04) and in particular for HPV genotypes 31/33/35 (p = 0.02) and 6/11 (p = 0.07). In contrast, similar analysis of the HIV-negative subset showed that a positive antibody test for syphilis was associated with HPV (p = 0.03). Anal epithelial abnormalities were found in 13 (14%) of 92 technically adequate cytologic smears and were strongly associated with detection of any HPV genotypes by the dot-blot method (p = 0.01), and in particular with HPV genotypes 6/11 (p = 0.001). None of 15 subjects with HPV detected only by PCR had anal epithelial abnormality. We propose a viral interaction model, in which HIV-related immune deficiency allows reactivation of HPV, with a subsequent or concomitant appearance of epithelial abnormality.

Decreased helper T lymphocytes in homosexual men. I. Sexual contact in high-incidence areas for the acquired immunodeficiency syndrome.

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.

Decreased helper T lymphocytes in homosexual men. II. Sexual practices.

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.

Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus.

We prospectively evaluated potential markers and cofactors for the acquired immunodeficiency syndrome (AIDS) in 86 homosexual men who were seropositive for human immunodeficiency virus antibodies. During three years of follow-up, 19 men developed AIDS. Risk of AIDS was clearly predicted by the total number of circulating OKT4-positive lymphocytes (T4 count) at enrollment, while the corresponding T8 count was unrelated to subsequent AIDS development. Subjects in Manhattan had a higher risk of Kaposi's sarcoma than did subjects in Washington, DC, and the risk of AIDS tended to increase with numerous homosexual partners. Several of 40 potential cofactors defined ex post facto, including receptive fellatio, enemas, methaqualone use, and high levels of antibody to hepatitis B surface antigen, appeared to be associated with Kaposi's sarcoma but not with Pneumocystis pneumonia. Our data suggest that potent cofactors for Pneumocystis pneumonia were not prominent, pointing to the need for effective drug therapies, particularly to reduce the high AIDS risk of persons with human immunodeficiency virus infection and low T4 counts.