Brian Willoughby

Progression to AIDS and predictors of AIDS in seroprevalent and seroincident cohorts of homosexual men.

As part of an ongoing prospective study of seropositive homosexual men in Vancouver, Canada, a seroprevalent cohort of 246 subjects (i.e. duration of infection unknown) and a seroincident cohort of 102 subjects (i.e. duration of infection known) were followed a median of 63 and 45 months, respectively. Follow-up with validation utilizing record linkage with the Canadian Federal Centre for AIDS registry revealed 58 and nine cases of AIDS in the seroprevalent and seroincident cohorts, respectively, through July 1988. These data yield product limit estimates of the cumulative progression rates to AIDS at 60 months of 23.0% for the seroprevalent cohort, 13.0% for the seroincident cohort, and 21.0% for the combined groups. Univariate analyses revealed the following to be statistically and clinically significant predictors of AIDS progression: low CD4 counts, low CD4/CD8 ratios, elevated immune complexes, elevated immunoglobulin G (IgG) and immunoglobulin A (IgA) levels, and low platelet counts. Cox regression revealed that elevated IgA levels, low CD4 counts, elevated immune complexes, two or more symptoms, and more than 20 male sexual partners in high-risk areas in the 5 years prior to enrollment were independent predictors of progression to AIDS over the subsequent 5 years. A multivariate risk function based on the latter five variables delineated low-, medium- and high-risk groups whose 5-year progression rates to AIDS were 6.7, 15.6 and 64.4%, respectively. The high-risk group contained 75% of all subjects who progressed to AIDS. Only 6% of the high-risk group would have qualified for zidovudine therapy under current guidelines at the beginning of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Susceptibility to AIDS progression appears early in HIV infection.

To investigate whether predictors of AIDS progression are operative very early in the natural history of HIV infection, we conducted a nested case-control study within a cohort of 119 subjects who seroconverted while under observation in a prospective study of homosexual men. For each of the 18 cases who have progressed to AIDS, we randomly Selected three controls who had seroconverted within 3 months of the case but who have remained AIDS-free. Cases and controls were compared with regard to laboratory and clinical parameters obtained at the time of the earliest HIV-positive result. The median duration between the estimated date of seroconversion and this first positive result was 4 months for cases and 6 months for controls. Cases exhibited lower CD4 counts (657 versus 774 × 106/I; P = 0.037), lower CD4:CD8 ratios (0.98 versus 1.39; P = 0.003), higher immune complex levels (C1q binding: 25 versus 15%; P = 0.002), lower hemaglobin concentrations (14.8 versus 15.2 g/l; P = 0.011), higher immunoglobulin (lg) A levels (272 versus 184mg/dl; P = 0.003), and higher lgG levels (1530 versus 1300mg/dl; P = 0.037) than controls. Cases exhibited higher CD8 counts of marginal statistical significance (732 versus 597 × 1.06/I; P = 0.059). No differences were observed with respect to lgM levels, total lymphocyte or white blood cell counts, or the frequency of generalized lymphadenopathy. A total of 27.8% of cases but only 11.5% of controls reported one or more symptoms during the 6-month period preceding the first positive visit (P = 0.027). We conclude that laboratory and clinical abnormalities which are predictive of more rapid progression to AIDS may appear very early in HIV infection. This suggests that some of the factors responsible for more rapid disease progression are present in the host prior to or shortly after infection occurs.

CHANGES IN SEXUAL BEHAVIOUR AND FEAR OF AIDS

A high number of sexual partners is strongly associated with the development of the acquired immunodeficiency syndrome (AIDS) in homosexual men. We are conducting a cohort study in 800 homosexual males in Vancouver. Recruitment was done between November 1982 and February 1984 through 6 general practices which cater entirely or predominantly for homosexual men. Volunteers completed a self-administered questionnaire at the time of enrollment giving demographic historical and lifestyle information. Questions about sexual practices were posed in the widely used vernacular. A 2nd questionnaire was administered at least 3 months later at the 1st follow-up visit. The 2nd questionnaire asked about changes in sexual practice since enrollment in the study. So far we have follow-up data for 388 men. Over half reported a decrease in the number of sexual partners. The proportion of respondents reporting no more than 5 partners per year rose from 21% to 37%. Specific sexual practices were more likely to have decreased than increased except for oral-genital contact. This is more striking for the 4 less popular sexual activities than for anal intercourse. Golubjanikov et al. have noted a decline in number of sexual partners for a clinic-based homosexual population in Wisconsin. Our population recruited through general practitioners with an enrollment rate of 95% among those asked to participate is likely to be fairly representative of the homosexual community. However the mere fact of participation in an AIDS-related study might have had an educational effect and the observed changes may be inflated. Nevertheless the evidence points to a decline in overall sexual activity and also in certain specific activities a selectivity that might stem from differences in risk of AIDS as perceived by homosexuals. It is not clear if a decrease in sexual activity is related to the recent decline in the incidence of AIDS. (full text)