E138A in HIV-1 reverse transcriptase is more common in subtype C than B: Implications for rilpivirine use in resource-limited settings

•We looked for genetic differences at RPV resistance codons among HIV-1 subtypes.•E138A was found to occur more frequently in subtype C than B HIV-1 sequences.•E138A could impact RPV therapy in resource limited settings. The nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV) has been co-formulated with emtricitabine and tenofovir disoproxil fumarate for initial therapy of HIV-1-infected individuals. RPV, formulated as a long-acting nanosuspension, will also be assessed for its ability to prevent HIV-1 infection in resource limited settings. In this study, we determined whether any pre-existing genetic differences occurred among different HIV-1 subtypes at residues in RT associated with decreased virologic response to RPV. We found that the E138A substitution occurs more frequently in subtype C (range: 5.9–7.5%) than B (range: 0–2.3%) sequences from both treatment-naïve and -experienced individuals (p