Lower CD4 cell count and higher virus load, but not antiretroviral drug resistance, are associated with AIDS-defining events and mortality: An ACTG Longitudinal Linked Randomized Trials (ALLRT) analysis

Background: We hypothesized that drug resistance mutations would impact clinical outcomes associated with HIV-1 infection. Methods: A matched case-control study of participants in AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT). Cases experienced an AIDS-defining event (ADE) or mortality, and controls did not. One hundred thirty-four cases were identified and matched to a total of 266 controls by age, sex, treatment regimen, and length of follow-up. Both cases and controls had HIV RNA levels of ≥500 copies/mL within 24 weeks of an event. Population-based genotyping at or near the time of the event was used to evaluate the impact of resistance mutations on incidence of ADE and/or death using conditional logistic regression models. Results: One hundred four cases and 183 controls were analyzed. Median time to event was 99 weeks; 6 cases were deaths. At baseline, cases had lower CD4 (median 117 vs 235 cells/mm ³; P < .0001) and higher HIV RNA levels (median 205,000 vs 57,000 copies/mL; P = .003). No significant differences in resistance were seen between cases and controls. Conclusions: In this rigorously designed case-control study, lower CD4 cell counts and higher virus loads, not antiretroviral drug resistance, were strongly associated with ADE and mortality.