Abstract
IntroductionRilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naïve individuals with HIV-1 viral load of <100,000 copies/ml. As transmission of the drug resistance mutations to this NNRTI may affect treatment outcomes, the frequency of primary, RPV-associated drug resistance mutations was assessed in this study.MethodsFor the study, 244 viral genome sequences from antiretroviral-naïve individuals were obtained by bulk sequencing. RPV-associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data.ResultsIAS-USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non-B clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering of RPV mutations was infrequent.ConclusionsPrevalence of RPV-associated drug resistance mutations was low in the analysed sample and did not vary across the subtypes. The frequency of variants with potential influence on RPV susceptibility was similar among non-B variants if compared to B clades. Transmitted drug resistance to RPV is uncommon, which makes this a good option for the treatment of ARV-naïve patients; however, genotype resistance testing should remain compulsory before starting an RPV-based regimen.
Highlights
Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naıve individuals with HIV-1 viral load of B100,000 copies/ml
That analysis of the ECHO and THRIVE clinical data indicated that the presence of V90I, V106I, V179I and V189I was not associated with virological failure; these mutations are not likely to be associated with RPV resistance in vivo [19]
RPV resistance-associated mutations were divided into key resistance mutations (K101E/P, E138A/G/K/Q/R, V179L,Y181C/I/V, Y188L, H221Y, F227C and M230I/L) based on the International AIDS Society-USA (IAS-USA) drug resistance mutations list update 2013 [12] and potential drug resistance mutations (L100I, K101H/T, E138S, V179F/D/ G/T, G190A/E/S, F227L and M230V) based on the clinical trial and in vitro data with the exclusion of mutations not associated with virological failure [13Á19]
Summary
Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naıve individuals with HIV-1 viral load of B100,000 copies/ml. Major RPV resistance-associated mutations have been included in the International AIDS Society-USA (IAS-USA) guidelines with K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L, as well as the recently added Y188L, defined as associated with key resistance [12]. I n numerous in vivo and in vitro studies, other candidate drug resistance mutations have been identified, including V90I, L100I, K101H/T, V106L, E138S,V179F/D/G/I/T, V189, G190A/E/ S, F227L and M230V [13Á18] It must be noted, that analysis of the ECHO and THRIVE clinical data indicated that the presence of V90I, V106I, V179I and V189I was not associated with virological failure; these mutations are not likely to be associated with RPV resistance in vivo [19]
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