The use of plasma HIV RNA as a study endpoint in efficacy trials of antiretroviral drugs.

Objectives: To evaluate the utility of HIV RNA as an endpoint in antiretroviral efficacy studies.

Design: Data collected from antiretroviral efficacy trials were analyzed to explore relationships between clinical progression and the magnitude, nadir and duration of HIV RNA reductions. The proportion of patients suppressing HIV RNA below assay quantification, time to maximal virologic response, and loss of virologic response in relation to pretreatment characteristics were also analyzed.

Methods: Analyses were conducted using data from individual antiretoviral efficacy trials or groups of trials that studied similar types of drug regimens and used similar HIV RNA assays. Treatment regimens were pooled for most analyses. Clinical progression was defined as the occurrence of an AIDS-defining event (essentially Centers of Disease Control criteria) or death.

Results: Treatment-induced reductions in HIV RNA approximating total assay variability of about 0.5 log10 copies/ml were associated with decreases in the risk of clinical progression. Larger and more sustained reductions in HIV RNA were directly associated with lower risks for disease progression. Lower initial HIV RNA reductions were associated with more durable HIV RNA suppression.

Conclusions: For antiretoviral efficacy studies, plasma HIV RNA is a suitable study endpoint that is likely to predict a decreased risk for AIDS progression and death. Because greater and more sustained reductions in HIV RNA appear to confer greater reductions in clinical risk, maintaining maximal suppression of plasma HIV RNA, particularly below the limits of assay quantification, appears to be a rigorous benchmark for assessing the efficacy of antiretroviral regimens.