literature

Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia.

PMID: 35458459 2022 Viruses

Introduction: Similarly, R263K is mainly present in subtype B, while G118R has a pathway in selecting DTG resistance in non-B subtype viruses.

Result: In this study,19 substitutions conferring major resistance to DTG at 10 amino acid positions in the IN (T66A/I/K, E92G, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H, and R263K) were assessed to explore the genetic barrier to DTG.

Result: No major DRMs known to be associated with DTG resistance (

PMID: 34534138 2022 AIDS (London, England)

Result: M184V was detected at week 132 and R263R/K was detected at week 144 in one participant in the DTG + 3TC group.

Result: The central laboratory initiated resistance testing using samples from the week 132 and 144 visits: M184V at week 132 (SVW criteria time point) was confirmed; at week 144, both M184V and the DTG resistance-associated mutation mixture R263R/K were detected, the latter conferring a 1.8-fold change in susceptibility to DTG.

Discussion: In these larger, fully powered, randomized GEMINI-1 and GEMINI-2 studies, 1 participant with transiently increased HIV-1 RNA levels late in the study period (week 132; did not meet CVW criteria) developed the M184V and R263R/K mutations.

Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.

PMID: 34694877 2022 Antimicrobial agents and chemotherapy

Abstract: G118R or R263K increased the rate of dolutegravir dissociation from integrase-DNA complexes versus wild-type but retained prolonged binding.

Abstract: Of participants who received dolutegravir through week 48 plus an additional 110 weeks for this assessment, 6 met CVW criteria with treatment-emergent INSTI resistance-associated substitutions and 1 had R263R/K at baseline but not at CVW.

Abstract: Treatment-emergent G118R was detected in 5 participants, occurring with >=2 other integrase substitutions, including R263R/K, in 3 participants and without other integrase substitutions in 2 participants.

Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study.

PMID: 34694878 2022 Antimicrobial agents and chemotherapy

Discussion: In participant 1, the clustering of all week 36 and 136 clones containing R263K substitutions suggests a path of viral evolution.

Discussion: In the larger adult phase III studies DAWNING and SAILING, emergence of G118R and/or R263K with dolutegravir occurred in <2% of participants.

Discussion: Indeed, for participant 1, who had emergent R263K, there were reports of nonadherence to the optimized background regimen and only sporadic adherence to dolutegravir leading up to and after PDVF.

Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.

PMID: 34897227 2022 Journal of acquired immune deficiency syndromes (1999)

Introduction: Primary INSTI drug resistance reported in surveillance studies are mainly substitutions that cause resistance to RAL and EVG (T66A/I, E92Q, Y143C/H/R, S147G, Q148H/K/R, and N155H pathways) and R263K, which confers low-level reduced susceptibility to EVG, DTG, and bictegravir (BIC).

Table: R263K

Discussion: R263K on its own causes small increases in fold change that may not be clinically relevant, but when it is selected in vitro along with secondary mutations such as

Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort.

PMID: 35207677 2022 Journal of personalized medicine

Method: We also excluded PWH with the following INSTI mutations: T66I, E92Q, G118R, G140S, Y143A/C/G/H/K/R/S, S147G, Q148H/K/N/R, N155H/S/T, and R263K.

High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort.

PMID: 35215866 2022 Viruses

Result: The mutations conferring resistance to DTG, the newly introduced and WHO recommended INSTI, include E138K (IN), G118R, and R263K with prevalences of 6%, 3%, and 2%, respectively.

Discussion: R263K, a variant shown to be selected by DTG in vitro, was present in 2.3% of our sample with a mean quasispecies frequency of 34.9% (Figure 1), a startling prevalence considering that DTG is a relatively new drug and newer INSTIs have a high genetic barrier to resistance.

Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression.

PMID: 35274144 2022 The Journal of antimicrobial chemotherapy

Abstract: R263K was only found at extremely low levels (0.07%).

Abstract: Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, score = 30 Stanford HIVDB 9.0).

Abstract: We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia.

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.

PMID: 33807382 2021 Viruses

Introduction: INSTI-naive highly treatment-experienced patients failing DTG cART have been found to have a virus with DRMs including G118R, D67N; H51H/Y, G118R, E138E/K, and less commonly R263R/K, V260I, R263R, N155H, G118R, and E138E.

Method: The mutations of interest included: T66A/I/K, Discussion: Compared with a similar cohort of patients from clinical trials, the selection of major integrase DRM- R263K was common.

Integrase Strand Transfer Inhibitor Resistance in Integrase Strand Transfer Inhibitor-Naive Persons.

PMID: 33683148 2021 AIDS research and human retroviruses

Abstract: Two surveillance DRMs, E138K and R263K occurred in 0.15% and 0.10% of naive sequences, respectively.