Emergent HIV-1 Drug Resistance in Randomized Trials of Contemporary Antiretroviral Regimens.

The occurrence of virological failure in a subset of individuals is an inevitable aspect of antiretroviral treatment, and historically has been primarily influenced by suboptimal adherence to oral therapies. The risk of selecting 1- or 2-class human immunodeficiency virus (HIV) drug resistance is influenced by the composition of the regimen, differing significantly depending on the intrinsic barrier to resistance of the regimen. HIV resistance emergence during treatment can be viewed as a regimen-related adverse effect that warrants equal consideration in clinical trials alongside virological and safety endpoints. Antiretroviral regimens demonstrating non-inferiority and showing similar rates of virological failure can nonetheless differ in terms of HIV emergent resistance. We propose the development of a systematic framework to categorize emergent HIV drug resistance in clinical trials. Standardizing the evaluation of resistance in clinical trials and its reporting to regulatory agencies will facilitate an improved understanding of regimen-specific resistance risks and better inform clinical decision making.