literature

HIV mutation literature information.

Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus.

PMID: 29077927 2018 The Journal of antimicrobial chemotherapy

Abstract: A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with >=1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015).

Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1.

PMID: 28923862 2017 Antimicrobial agents and chemotherapy

Abstract: In multiple rounds of infection, the G140S/Q148H combination of substitutions decreased HIV-1 susceptibility to BIC 4.8-fold compared to 16.8- and 7.4-fold for CAB and DTG, respectively.

Dolutegravir monotherapy as treatment de-escalation in HIV-infected adults with virological control: DoluMono cohort results.

PMID: 27588613 2017 Antiviral therapy

Abstract: One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S).

Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome.

PMID: 28212411 2017 PloS one

Introduction: As a secondary INSTI RAM, T97A further reduces INSTI susceptibility and/or rescues viral fitness in association with Y143C/R, Q148H+G140S, or N155H.

Method: Primary INSTI RAMs against EVG and/or RAL were based on IAS-USA Guidelines of RAMs with some modifications to remove secondary INSTI RAMs (i.e., L74M, F121Y, E138A/K, and G140A/S) (Fig 1).

Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.

PMID: 28369593 2017 The Journal of antimicrobial chemotherapy

Abstract: For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one).

Impact of HIV-1 Integrase L74F and V75I Mutations in a Clinical Isolate on Resistance to Second-Generation Integrase Strand Transfer Inhibitors.

PMID: 28533248 2017 Antimicrobial agents and chemotherapy

Abstract: Addition of L74F V75I to N155H or G140S Q148H increased resistance levels to the second-generation INSTIs dolutegravir (>385- and 100-fold, respectively) and cabotegravir (153- and 197-fold, respectively).

Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128).

PMID: 28891788 2017 HIV clinical trials

Method: Secondary INSTI-R substitutions assessed were M50I, H51Y, L68I/V, V72A/N/T, L74M, Q95K/R, G118R, S119P/R/T, F121C/Y, A128T, E138A/K, G140A/C/S, P145S, Q146I/K/L/P/R, V151A/L, S153A/F/Y, E157K/Q, G163K/R,

Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors.

PMID: 29137637 2017 Virology journal

Method: Major INSTI resistance mutations (T66I, E92Q, F121Y, Y143CHR, S147G, Q148HKR, N155H) that confer substantial phenotypic resistance to at least one of the currently approved INSTI as well as minor INSTI resistance mutations (T66AK, L74 M, E92G, T97A, E138AK, G140AS, R263K) that increase INSTI resistance and/or viral

Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of Dolutegravir Fluorescence.

PMID: 29070877 2017 Scientific reports

Abstract: We also compared dolutegravir-binding to PFV F190Y, G187R and S217K mutants, corresponding to HIV-1 F121Y, G118R and G140S/Q148K mutations that confer low-to-high resistance levels against raltegravir/dolutegravir.

Introduction: Our findings define a new approach to study the binding properties of DTG to IN and reach deeper insight into the mechanisms of drug resistance mutations such as G187R, F190Y and S217K (equivalent to G118R, F121Y and G140S/Q148K mutations, respectively, in INHIV).|mg

Monotherapy with either dolutegravir or raltegravir fails to durably suppress HIV viraemia in humanized mice.

PMID: 28637235 2017 The Journal of antimicrobial chemotherapy

Abstract: The virus from this mouse had mutations E138K, G140S, Q148H, N155H and S230R, was highly resistant to both raltegravir (EC50 of >1000 nM) and dolutegravir (EC50 of 550 nM), and replicated to levels similar to those of control viruses in PBMCs.

Abstract: Viruses from raltegravir failing mice developed mutations G140G/S and Q148H/K, and were resistant to both raltegravir (EC50 values of >100 nM) and dolutegravir (EC50 values ranging from 8.8 to 13.3 nM).

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