Estimating the Optimal CD4 Count for HIV-infected Persons to Start Antiretroviral Therapy

Background: Optimal timing of antiretroviral therapy in HIV-infected persons is unclear, although 2 recent large observational studies have improved our understanding of the best CD4 threshold for initiation. These studies compared the effect of starting HAART on mortality and mortality/AIDS between strata defined using broad ranges of CD4 counts. We sought to expand this understanding using a novel statistical approach proposed by Robins et al. Methods: Using observational data from 1034 antiretroviral-naive HIV-infected patients from Nashville, Tennessee, we directly estimated the optimal CD4 count for initiation of HAART to maximize patient health 6, 12, 24, and 36 months after the first instance of CD4 falling below 750. We measured health using 2 outcome metrics, one based on CD4 counts at the end of follow-up and the other based on a published quality-of-life scale; both metrics incorporated death, AIDS-defining events, serious non-AIDS events, and CD4 at the end of follow-up, if asymptomatic. Results: The CD4-based metric estimated that to maximize health 6, 12, 24, and 36 months after study entry, HAART should be initiated within 3 months of CD4 first dropping below 495 (95% confidence interval [CI] = 468-522), 554 (459-750), 489 (427-750), and 509 (460-750), respectively. The quality-of-life-based metric produced CD4 initiation threshold estimates of 337 (95% CI = 201-442), 354 (288-386), 358 (294-750), and 475 (287-750) for the same time points. Conclusions: Our results support early initiation of antiretroviral therapy, although the criterion for starting therapy depends on the choice of health outcome.