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 individualʹs 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 ≤ 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.