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.
Discussion: Notably, i
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
Result: Two of 3 participants with G118R plus other
Table: R263R/K
Discussion: G118R emerged in combination with >=3 other integrase substitutions in 3 participants, including with R263R/K plus E138E/K in 2 participants.
Discussion: Most participants had integrase substitutions of G118R, either alone or in combination with other substitutions, including R263R/K.
Discussion: Unusually, 1 participant had the highly conserved integrase substitutions R263R/K and M184I/V as mixtures at baseline but not at CVW.
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
Result: Of the 8 participants with resistance-associated integrase substitutions, 6 had treatment-emergent rare INSTI-associated substitutions G118R (n = 5) or R263K/R (n = 1) during the course of treatment (Table 2).
Result: Testing at week 36 showed that virus from participant 1 had treatment-emergent R263K/R but was susceptible to dolutegravir (fold change, 1.1).
Table: R263R
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
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.
Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy.
PMID: 34189182
2021
Open forum infectious diseases
Discussion: Neither the M184V (RT) mutation nor the R263KR (INI) mutation was observed in the 2 pretreatment genotypes, suggesting that these were treatment-emergent mutations and were not transmitted or present at baseline.
Discussion: The M184V (RT) mutation was detected after 17 weeks of therapy, and at week 37 the R263KR (INI) mutation was detected via bulk sequencing (Viracor Lab, Missouri) necessitating a change in ART.
Discussion: Two other reported cases of the R263KR (INI) mutation have been in individuals with non-subtype B HIV type 1, both with advanced HIV disease
Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b.
PMID: 35008581
2021
International journal of molecular sciences
Result: For the missense mutation R263K with a DeltaHZEI of -132.16, a silent version R263R with a slightly lower DeltaHZEI of -107.8 was gen
Result: In between the two splice donors, the missense mutations V260I and R263K and the silent mutations V260V and R263R, as well as the parental sequence, were inserted (Figure 3A).
Result: Interestingly, the silent version R263R with a similar but even slightly lower DeltaHZEI of -107.8 showed only a slight decrease in SD2b recognition, compared with the parental NL4-3 sequence (Figure 3B).
Result: To further analyze the silent mutation R263R, the mutation was inserted into the pNL4-3 proviral plasmid by site-directed mutagenesis and used for infection.
ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.
Abstract: Three participants with VF, had undetected plasma dolutegravir at >=1 time points; the M184V and R263R/K mutations developed in 1 participant.
Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir.
Introduction: In contrast, very few patients in the DTG arm developed new drug resistance although the viral isolates from two individuals with protocol-defined virological failure (PDVF) after 24 weeks of treatment were found to have developed a R263K integrase substitution or a R263K/R mixture.
Introduction: Nor did the R263K/R mixture further evolve towards a pure R263K population.
HIV mutation literature information.
PMID: 
2022
AIDS (London, England)
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