Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: Implications for when to initiate therapy

Background. The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear. Methods. Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART. Results. Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at 1350 CD4 cells/muL, but mortality was higher both in participants with >350 CD4 cells/muL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/muL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts <200 cells/mu L. Conclusions. Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts >350 cells/muL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.