Application of case-crossover and case-time-control study designs in analyses of time-varying predictors of T-cell homeostasis failure.

PURPOSE To evaluate the association of sexual behavior and recreational drug exposures with T-cell homeostasis failure (TCHF), which corresponds to the onset of a rapid decline in an individual's T lymphocyte count, which occurs on average approximately 1.75 years prior to an initial diagnosis of acquired immunodeficiency syndrome (AIDS). METHODS A case-crossover design and a case-time-control design, both nested within the Multicenter AIDS Cohort Study of 4954 homosexual and bisexual men initiated in 1983. RESULTS In the case-crossover analysis, use of both recreational drugs and hashish were found to be protective against TCHF (odds ratios < or = 0.41), based on comparisons with four earlier control periods. However, a significant decreasing trend in the prevalence of these exposures was observed over time, thus motivating the implementation of the case-time-control design. Using the latter approach, the associations of drug use (odds ratio=0.53; 95% confidence interval (CI): 0.22, 1.28) and hashish use (odds ratio=0.46; 95% CI: 0.20, 1.05) with TCHF were no longer statistically significant. CONCLUSIONS The difference in inferences between these approaches demonstrates the importance of evaluating temporal trends in exposures when using a case-crossover design.