Mary M. Fanning

Using serial observations to identify predictors of progression to aids in the Toronto Sexual Contact Study

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Pilot study of sandostatin (octreotide) therapy of refractory HIV-associated diarrhea.

Seventeen AIDS patients were enrolled in a prospective open-label dose-finding study of octreotide (Sandostatin) therapy for refractory diarrhea. Five were nonevaluable due to progression of AIDS symptomatology, and one was excluded because of lack of confirmation of HIV infection. Five of 11 evaluable patients responded to therapy (45%); two each at 50 μg and 100 μg, and one at 250 μg thrice daily doses. A sixth patient demonstrated a moderate reduction in stool volume at 250 μg thrice daily, which, although deemed clinically relevant, did not meet the criteria for response. On discontinuation of therapy, diarrhea recurred in all patients within 1–12 days, and responded to reinitiation of octreotide in those five patients who resumed treatment. Only one of the three patients with concurrent cryptosporidial infection responded to treatment. The drug was well tolerated, with mild symptomatology in three patients. Long-term treatment at a stable dose was effective in three of five treated patients for periods for seven months in one (moderate responder) and one year in two. One patient required dose increases to control symptoms, but after one year of treatment developed severe nausea following injections, which required dose cessation. One patient had partial control of his diarrhea for only three months despite two dose increases. These data suggest that octreotide may be of useful therapeutic value in HIV-associated diarrhea and that further studies are indicated.

Ongoing high-risk sexual behaviors in relation to recreational drug use in sexual encounters Analysis of 5 years of data from the Toronto sexual contact study

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.

Assessment of generalized lymphadenopathy in aids research: The degree of clinical agreement

The degree of clinical agreement amongst different physicians on the presence or absence of generalized lymphadenopathy was assessed in 32 randomly selected participants from a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition (ARC). Three physicians completed the same standard examination that was developed for the main project and conducted the examination of the anatomic regions in the same order on each person, at approximately the same time, and in random order. One physician (Doctor A) was the physician responsible for conducting examinations on the main cohort from which these participants were selected. Intra-observer agreement was assessed by comparing Doctor As examinations on these participants with those he had recently conducted within a one and a half month period in the main study. Acceptable levels of intra-observer agreement (kappa = 0.72) and interobserver agreement (kappa = 0.66) were demonstrated for the presence or absence of generalized lymphadenopathy for Doctor A and Doctor B, a physician who periodically replaced Doctor A in the main project. Agreement between Doctors A, B, and C, was less satisfactory (kappa of 0.45 and 0.39, respectively). Doctor C was the least experienced with the standardized examination. However, during the progress of this study, agreement between the three doctors improved (kappa values for the latter 16 participants ranged from 0.60 to 0.86) suggesting that experience with the criteria and the standardization of the examination may enhance agreement.(ABSTRACT TRUNCATED AT 250 WORDS)