Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults

Abstract

We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation.

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

“…Of note, these frequencies raised up to 8.1% and 7.7% respectively when polymorphic mutation E138A is included and to 9.5% and to 8.2 when all NNRTI combinations are considered. E138A mutation (always as isolated mutation) was detected mostly in patients with subtype B, who are the 67.3% of our study population, with a prevalence comparable to that described by Alvarez et al [28] in a Spanish cohort of naive patients recruited in the period 2007-2011: however in this study no data on patient's HIV genotype was included. Analysis by genotype was available in a French study including patients tested from 2008 to 2011: only half of patients had a B subtype virus and E138A was found in 2% of them, versus 4.1% in non-B subtype viruses [29].…”

HIV Drug Resistance in Antiretroviral Treatment-Naïve Individuals in the Largest Public Hospital in Nicaragua, 2011-2015

“…Also of interest, a large cluster of patients with the E138A mutation was observed, including both females and males (MSM and heterosexual). The higher prevalence of this resistance mutation to rilpivirine in specific geographic areas, including Latin America has been previously observed [ 35 – 41 ]. In the present study, E138A frequency was 4.2% using Sanger sequencing.…”

Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection

“…To address the former, long-acting injectable formulations of antiretroviral agents, notably the investigational integrase inhibitor cabotegravir and the secondgeneration non-nucleoside reverse transcriptase inhibitor rilpivirine, are being considered for use as PrEP [10][11][12]. However, whereas HIV-1 variants resistant to TDF are still relatively uncommon in most areas [13,14], and integrase-resistant variants rarer still [15], rilpivirine-resistant variants, in particular those with mutations at the 138th position of HIV-1 reverse transcriptase (RT-E138X), occur naturally at a significant frequency in some areas [14,[16][17][18]. Indeed, was previously shown to be significantly enriched among HIV-1 subtype B infected individuals carrying the Human Leukocyte Antigen (HLA) class I-B*18 allele [19,20]; RT-E138X variants were later confirmed to be HLA-B*18restricted CD8+ cytotoxic T lymphocyte (CTL) escape mutations occurring at the second (HLA/peptide anchor) position of a B*18-restricted CTL epitope spanning HIV-1 reverse transcriptase codons 137-144 [21].…”