Early antiretroviral therapy: the role of cohorts

Abstract

Purpose of review: To review the data that contribute to the debate on the optimal time to initiate highly active antiretroviral therapy in HIV-infected individuals, with a focus on the information that is available from cohort studies.

Recent findings: The findings from cohort studies generally support initiation of highly active antiretroviral therapy at CD4 cell counts more than 350 cells/microl. In particular, the findings that death rates among treated HIV-infected individuals are higher than those in the general population, and that the risks of AIDS and serious non-AIDS events are higher in those with lower CD4 cell counts (even when the count remains >350 cells/microl), suggest that earlier initiation of highly active antiretroviral therapy may prevent some excess morbidity and mortality. However, given the lack of adjustment for lead-time bias in many analyses, the potential for residual confounding and the possible incomplete ascertainment of relevant outcomes in cohorts, it cannot be concluded that the benefits of highly active antiretroviral therapy when started at higher CD4 cell counts will outweigh the possible detrimental effects.

Summary: Whereas the data from cohort studies currently support initiation of highly active antiretroviral therapy at CD4 cell counts more than 350 cells/microl, there is an urgent need for data from randomized trials to inform this decision.