Rilpivirine versus etravirine validity in NNRTI‐based treatment failure in Thailand

Abstract

IntroductionEtravirine (ETR) and rilpivirine (RPV) are the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV-1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI-based regimen [1]. RPV has profile with similar properties to ETR but this agent is approved for treatment-naïve patients [2]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI-based regimens: efavirenz (EFV)- or nevirapine (NVP)-based regimen.Materials and MethodsData of clinical samples with confirmed virologic failure during 2003–2010 were reviewed. We selected the samples from patients who failed EFV- or NVP-based regimen. Resistance-associated mutations (RAMs) were determined by IAS-USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV.ResultsA total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP-based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV-based regimen treatment failure (EFV group) were included. 95% of samples were HIV-1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI-RAMs and 20% had four to seven NNRTI-RAMs. 181C mutation was the most common NVP-associated RAM (54.3% vs 14.7%, p<0.01). 103N mutation was the most common EFV-associated RAM (56.5% vs 19.1%, p<0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly higher than NPV group (ETR susceptibility 32.2% vs 11.1%, p<0.01, RPV susceptibility 31.6% vs 10.9%, p<0.01), respectively.ConclusionsRPV might be a cost saving and reasonable second line NNRTI for patients who failed EFV- or NVP-containing regimens, especially in resource-limited setting because these two agents have comparable susceptibility identified by genotyping. From our study, approximately 30% of patients who failed EFV-based regimens had viruses that remained susceptible to RPV.

Rilpivirine and Etravirine resistance among HIV-1 infected patients failing first generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) in Busia, Western Kenya

“…Saravanan et al (2017), reported 47% and 65% ETR and RPV resistance profiles respectively, contrary to our current study which reported similar percentages of resistance profiles between ETR and RPV (both with 45.7% resistance). Teeranaipong et al (2014) reported 32.2 and 31.6% susceptibility in ETR and RPV, respectively which was in concordance with the results of this study. There is therefore a need for more studies to clearly define the prevalence of ETR and RPV-associated mutations in populations receiving first-generation NNRTIs especially sub-Saharan Africa.…”

High prevalence of PI resistance in patients failing second-line ART in Vietnam

“… 47 , 48 High prevalence of cross-resistance to etravirine (60%) has been reported in several studies of CRF01_AE-infected patients in Thailand for whom first-line NNRTI-based therapy was failing. 52 – 54 As efficacy data of etravirine use in south-east Asia are lacking, phenotypic assays investigating the in vitro susceptibilities of these clinical isolates would be helpful. Until then, etravirine and rilpivirine should probably be avoided as third-line drugs for patients infected with subtype CRF01_AE in south-east Asia.…”