Application of case-crossover and case-time-control study designs in analyses of time-varying predictors of T-cell homeostasis failure.
OBJECTIVE
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.
Schneider
Michael F
MF
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. mschneid@jhsph.edu
Gange
Stephen J
SJ
Margolick
Joseph B
JB
Detels
Roger
R
Chmiel
Joan S
JS
Rinaldo
Charles
C
Armenian
Haroutune K
HK
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D018592:Cross-Over Studies; D006706:Homeostasis; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D012107:Research Design; D019966:Substance-Related Disorders; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors