Dolutegravir Monotherapy of Simian Immunodeficiency Virus-Infected Macaques Selects for Several Patterns of Resistance Mutations with Variable Virological Outcomes.
Abstract: Some mutations, such as G118R, previously shown to severely impair the replication capacity in vitro, were associated with more sustained virological and immunological benefits of continued DTG therapy, while other mutations, such as E92Q and G140A/Q148K, were associated with more variable outcomes.
Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART.
PMID: 30380053
2019
The Journal of antimicrobial chemotherapy
Discussion: We did observe Q148R, which is associated with high-level dolutegravir resistance when accompanied by the G140S/A mutations.
Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.
Introduction: The resistance patterns observed in HIV-1 patients on a raltegravir containing regimen are very diverse and Q148H/K/R (usually with G140A/C/S and/or E138A/K) and N155H (often together with E92Q or V151I) mutations are observed more frequently than Y143 mutations.
Result: G140S was probably not selected because it required two nucleotide changes in this HXB2 background; G140A and E138K required just one.
Result: Two of the Q148K mutations were accompanied by G140A, the third by E138K.
Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir.
Introduction: Drug resistance is associated with the accumulation of primary resistance substitutions and relevant compensatory substitutions along several pathways including the (1) N155H and G140A/G148R/H/Q pathways conferring high level cross-resistance to RAL and EVG; (2) the T66I or E92Q/G pathways leading to resistance to EVG; or (3) the Y143R/H/C RAL-specific resistance pathway.
Table: G140A
Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes.
Result: Five patients (21%) with multiple mutations (Q148QR+N155H, G140A+Q148R, E138K+G140S+Q148R, E138K+G140A+ S147SG+Q148K and G140S+Q148H+N155H) were predicted to have high-level cross resistance to DTG, CAB, and BIC, although no phenotypic assessment has confirmed this observation.
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).
Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors.
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
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).
HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters.
PMID: 28472323
2017
The Journal of antimicrobial chemotherapy
Introduction: Resistance to elvitegravir and raltegravir occurs via several mutational pathways, including: (i) N155H or G140A/G148RHQ pathways conferring raltegravir and elvitegravir cross-resistance; (ii) T66I or E92Q/G elvitegravir-specific pathways; or (iii) the Y143R/H/C raltegravir-specific resistance pathway.
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).
HIV mutation literature information.
PMID: 
2019
Journal of virology
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