Is the time from HIV seroconversion a determinant of the risk of AIDS after adjustment for updated CD4 cell counts?

Objective: To evaluate the effect of time from seroconversion to a (riven C D4 cell count on progression to AIDS after that count after adjusting for u pdated CD4 cell counts. Methods: Using pooled data from 19 seroconverter cohorts, we examined the a ssociation between the time from a CD4 < 500 cells/mm(3), (< 350, < 200) to the first AIDS-defining event and time from seroconversion to that CD4 thr eshold. We adjusted for age, gender, exposure category, and HIV test interv al in Cox models stratified by cohort. We estimated the residual effect of time from seroconversion, adjusting for updated CD4 cell counts. A cause-sp ecific competing-risks model was then used to evaluate this residual effect on progression to each AIDS-defining disease. Analyses were censored on De cember 31, 1995. Results: Of 3825, 3006, and 1804 individuals reaching CD4 thresholds of 500 , 350, and 200, respectively, 1274, 1192, and 985, respectively, developed AIDS. We found a significant effect of time from seroconversion on the risk of AIDS even after adjusting for updated CD4 counts. For individuals reach ing a CD4 threshold of 350 Cells/mm(3), a 1-year increase from seroconversi on was associated with an increase in risk of AIDS of 6% (3%-9%) (p = .01). This effect appeared to be nonlinear. In the first 4 years, a 1-year incre ase from seroconversion was associated with an 11% increase in the risk of AIDS, but there was no apparent increase in risk after 4 years. The residua l effect of time from seroconversion was significantly heterogeneous (p = . 002), with respect to the risk of individual AIDS-defining diseases. Findin gs were similar for CD4 thresholds of 500 and 200 cells/mm3, respectively. Conclusions: We found a small, statistically significant, residual effect o f time from seroconversion on the risk of AIDS. In practical terms, when co nsidering an infected individual's risk of AIDS from a given CD4 cell count , there is little to be gained from knowing the time of seroconversion. How ever, this effect differs significantly among specific AIDS-defining diseas es.