literature

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

PMID: 35458459 2022 Viruses

Conclusion: The genetic barrier analysis showed that subtype C had a high genetic barrier to acquiring the G140C and G140S mutations, highlighting that the Q148H/K/R mutation DTG resistance pathway was selected less in subtype C.

Result: Similarly, a two-point mutation (one transversion and one transition) (minimum score of 3.5) was required to mutate to G140S (GGG/A to AGT/C) for subtype C; while subtype B required a one-step transition (minimum score of 1) (GGC to AGC).

Discussion: A similar high genetic barrier to acquire mutations G140S or G140C has also been described in CRF02_AG compared with subtype B.

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

Discussion: One participant in DAWNING had emergence of the integrase substitutions E138K, G140S, Q148H, and N155H.

Discussion: Similar to the participant from the present study, G140S and Q148H also emerged together with E138K and N155H in a participant who received dolutegravir monotherapy.

Discussion: Treatment with raltegravir and elvitegravir frequently selects for G140S and Q148H in combination, although emergence of major INSTI resistance-associated substitutions together, such as Q148H and

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

Table: G140A/C/S

Discussion: As observed in the viremic individual in this study, BIC has broader phenotypic activity than other INSTIs, including DTG, against clinical isolates with Q148H + G140S combinations.

Discussion: For example, the combination of Q148H/K/R and G140A/C/S in the presence of additional substitutions can cause high-level resistance to BIC (>10-fold change in phenotype compared with wild type) but as was seen with the naive case presented in this study, the Q148H+G140S pattern can also be susceptible to BIC.

Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study.

PMID: 35061879 2022 The Journal of antimicrobial chemotherapy

Abstract: Addition of E138K to G140S/Q148H conferred 35.5, 11.6 and 208-fold reduced susceptibility to dolutegravir, bictegravir, and cabotegravir, while addition of T97A to G140S/Q148H conferred 318, 121 and >1000-fold reduced susceptibility to these drugs.

Abstract: BACKGROUND: Routine HIV drug resistance genotyping identified an integrase sequence harbouring T97A, E138K, G140S and Q148H, with high predicted resistance to all integrase strand transfer inhibitors (INSTIs).

Abstract: Notably, bictegravir EC50 was significantly

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.

Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-nNaive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1.

PMID: 35240975 2022 Current HIV research

Abstract: Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients.

Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations In HIV-2 Integrase: A Phenotypic Analysis Using An Expanded Panel of Site-Directed Mutants.

PMID: 35134180 2022 The Journal of infectious diseases

Abstract: HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the EC50 for raltegravir when introduced into one or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance.

Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals.

PMID: 33800269 2021 International journal of environmental research and public health

Abstract: We identified the Q148HKR, G140S, Y143R, N155H, S147G, and E138EA major drug resistance mutations and the D232DN, T97TA, E157Q, G163GART accessory mutations.

Result: Interestingly, two samples, one collected in 2013 and the other in 2016, presented concurrently the mutations E138A, Discussion: However, the presence of three mutations (G140S, Q148H, and S147G) pose a higher risk of failing second-generation drugs.

Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants.

PMID: 33880558 2021 The Journal of antimicrobial chemotherapy

Abstract: One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144.

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

PMID: 33807382 2021 Viruses

Method: The mutations of interest included: T66A/I/K, E92Q, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H and R263K.

Discussion: It was recently shown that it is only upon the development of the T97A mutation that variants harboring Q148H and G140S Integrase mutations started to have increased VLs.