Is the time from HIV seroconversion a determinant of the risk of AIDS after adjustment for updated CD4 cell counts?
Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE Collaboration) None.
OBJECTIVE: To evaluate the effect of time from seroconversion to a given CD4 cell count on progression to AIDS after that count after adjusting for updated CD4 cell counts. METHODS: Using pooled data from 19 seroconverter cohorts, we examined the association 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 threshold. We adjusted for age, gender, exposure category, and HIV test interval in Cox models stratified by cohort. We estimated the residual effect of time from seroconversion, adjusting for updated CD4 cell counts. A cause-specific competing-risks model was then used to evaluate this residual effect on progression to each AIDS-defining disease. Analyses were censored on December 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 reaching a CD4 threshold of 350 cells/mm 3, a 1-year increase from seroconversion 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 increase 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 residual effect of time from seroconversion was significantly heterogeneous ( p =.002), with respect to the risk of individual AIDS-defining diseases. Findings were similar for CD4 thresholds of 500 and 200 cells/mm 3, respectively. CONCLUSIONS: We found a small, statistically significant, residual effect of time from seroconversion on the risk of AIDS. In practical terms, when considering 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. However, this effect differs significantly among specific AIDS-defining diseases.