The efficacy of first-line ART regimens based on RPV in HIV-infected patients with pre-existing E138A mutation in reverse transcriptase

Abstract

Introduction It was previously shown that the presence of the E138A mutation is associated with resistance to rilpivirine (RPV). Detection of this mutation is considered as contraindication for RPV use within the first-line ART. It is a lack of knowledge regarding efficacy of first-line RPV-based ART in patients bearing HIV with E138A mutation. In absence of HIV genotyping in naïve patients it may influence the clinical decisions.Methods We have collected all available patients unconventionally treated with RPV and carefully analyzed the ART efficacy in E138A carriers from the EuResist database. The viral load data in patients with E138A mutation at baseline was extracted from the database. Due to uniqueness of these cases only 11 HIV infected patients were found. The virologic outcome was analyzed according to the national and international ART guidelines.Results The full virologic efficacy of the first-line RPV-based ART regimen was demonstrated in 11 out of 11 patients according to all guidelines.Conclusions Our data suggest that the influence of the pre-existing E138A mutation on the sensitivity to RPV is very low or insignificant. The results support importance of investigation of polymorphic pre-existing HIV drug mutations for ART efficacy.

Notable transmitted HIV drug resistance among people who inject drugs in Pakistan

“…Over half (58.2%) of PWID in our study harbored E138A, conferring low-level resistance to the NNRTIs etravirine and rilpivirine (48,49). Other studies have observed E138A among people living with HIV in Pakistan, reporting varying prevalence in ART-experienced (13-78%)…”

“…NRTIs: K219R confers resistance to azidothymidine (41,42); and S68G is associated with K65R mutants to improve viral replication (43). NNRTIs: K101E confers highly-reduced susceptibility to nevirapine and decreases efavirenz, etravirine, and rilpivirine susceptibility (44); K103N is associated with resistance to nevirapine and efavirenz (45,46); V106I confers potential low-level resistance to doravirine, etravirine, nevirapine, and rilpivirine (47); E138A and E138Q confer reduced susceptibility to etravirine and reduced, potentially full, susceptibility to rilpivirine (48,49); V179D is associated with low-level resistance to efavirenz, nevirapine, etravirine, and rilpivirine (50); V179T has been reported with reduced susceptibility to etravirine in the presence of other DRMs (51); V179I is associated with resistance to etravirine and rilpivirine (52); and Y188H has been reported to confer resistance to nevirapine and efavirenz (53).…”