Low-Frequency Drug-Resistance Mutations and ART Failure

Genotypic HIV resistance testing prior to initiation of antiretroviral therapy (ART) is the standard of care in higher-income countries, because transmitted drug resistance is associated with increased risk for treatment failure, an outcome most commonly observed with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment. Standard assays detect mutations that constitute >15% of the virus population, whereas deep sequencing (pyrosequencing) and allele-specific polymerase chain reaction assays for selected mutations are much more sensitive. Whether the low-frequency mutations detected on these assays prior to treatment initiation influence virologic response to first-line ART is not yet clear.

To address this issue, investigato…