Transmission of HIV-1 drug resistance

Abstract

Infection with an HIV strain harboring drug resistance-related mutations is referred to as transmitted drug resistance (TDR) or primary resistance. As transmitted drug resistance increases the risk of virological failure, current guidelines recommend to perform drug resistance testing at baseline in all newly diagnosed individuals to guide the choice of antiretroviral therapy. The prevalence of TDR varies among regions, risk groups, and drug classes due to different exposure to antiretroviral therapy (ART), risk behavior, and access to therapy. Of concern in developed countries is the rising prevalence of mutations associated with NNRTI resistance, a drug class frequently used in firstline therapy which has a low genetic barrier for development of resistance. In resource-limited settings (RLS), rollout of ART with limited virological monitoring frequently results in the risk of prolonged virological failure with selection and accumulation of drug resistance mutations and subsequent transmission of drug resistance. Most surveys in RLS showed still low to moderate prevalence of TDR, but greater coverage of ART is associated with a higher prevalence of TDR. Also in RLS the rise in prevalence of TDR is mostly driven by NNRTI resistance, which is of particular concern as this drug class constitutes the foundation of current first-line ART regimens and prophylaxis for prevention of mother-to-child transmission.