Integrase Resistance–Associated Mutations on Raltegravir Failure in Western India: A Preliminary Analysis

Pujari, Sanjay; Gaikwad, Sunil; Joshi, Kedar; Dabhade, Digamber; Sane, Shrivallabh; Rao, Nalini; Bele, Vivek

doi:10.1097/qai.0000000000001625

Cited by 2 publications

(1 citation statement)

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“…This is not surprising because INSTIs have been primarily used in upper-income countries that have a lower prevalence of non-subtype B viruses, [37][38][39][40][41] with relatively small numbers of reports of INSTI resistance emanating from low-and middle-income countries. 42,43 WHO's 2018 ARV guidelines recommend the use of dolutegravir as preferred first-line ART. 5,6 It is expected that the new regimen will be adopted widely in many regions of the word, including settings with non-B subtype and where programmatic challenges, such as ARV drug stockouts, might result in the emergence of INSTI resistance and eventually its transmission.…”

Section: Jacmentioning

confidence: 99%

Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Tzou

Rhee

Descamps

et al. 2019

Journal of Antimicrobial Chemotherapy

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Background Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. Objectives We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. Methods To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presence on published expert lists, conservation in INSTI-naive persons, frequency in INSTI-treated persons and contribution to reduced in vitro susceptibility. Mutation prevalences were determined using integrase sequences from 17 302 INSTI-naive and 2450 INSTI-treated persons; 53.3% of the INSTI-naive sequences and 20.0% of INSTI-treated sequences were from non-B subtypes. Approximately 10% of sequences were from persons who received dolutegravir alone or a first-generation INSTI followed by dolutegravir. Results Fifty-nine previously recognized (or established) INSTI-resistance mutations were present on one or more of four published expert lists. They were classified into three main non-overlapping groups: 29 relatively common non-polymorphic mutations, occurring in five or more individuals and significantly selected by INSTI treatment; 8 polymorphic mutations; and 22 rare mutations. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. Conclusions A set of 24 non-polymorphic INSTI-selected mutations is likely to be useful for quantifying INSTI-associated TDR. This list may require updating as more sequences become available from INSTI-experienced persons infected with HIV-1 non-subtype B viruses and/or receiving dolutegravir.

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Section: Jacmentioning

confidence: 99%

Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Tzou

Rhee

Descamps

et al. 2019

Journal of Antimicrobial Chemotherapy

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Long-term treatment outcome and mutational analysis of patients on third-line antiretroviral therapy in programmatic conditions

Chakravarty

Srivastva

Kushwaha

et al. 2023

Journal of Antimicrobial Chemotherapy

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Background In low- and middle-income countries where most patients receive standardized third-line ART through national programmes, real-world data are scarce. This study was done to assess the long-term survival, and virological and mutational outcomes of people living with HIV receiving third-line ART between July 2016 and December 2019 in an ART centre in India. Methods Eighty-five patients were started on third-line ART. Genotypic resistance testing to identify drug resistance mutations in the integrase, reverse transcriptase and protease genes was done at the start of third-line therapy, as well as in those who did not attain virological suppression after 12 months of therapy. Results Survival was 85% (72/85) at 12 months and 72% (61/85) at the end of follow-up in March 2022. Virological suppression was present in 82% (59/72) and 88% (59/67) at 12 months and at the end of follow-up, respectively. Five out of 13 patients who had virological failure at 12 months showed virological suppression at the end of the study. At the start of third-line therapy, 35% (14/40) and 45% (17/38) of patients had major integrase- and protease-associated mutations, respectively, even though they had never been on integrase inhibitor-based regimens. At 1 year follow-up, among those failing third-line therapy, 33% (4/12) of patients had major integrase mutations, but none had major protease mutations. Conclusions This study demonstrates good long-term outcome in patients on standardized third-line ART in programmatic conditions with very few mutations in those failing the therapy.

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Integrase Resistance–Associated Mutations on Raltegravir Failure in Western India: A Preliminary Analysis

Cited by 2 publications

References 20 publications

Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Long-term treatment outcome and mutational analysis of patients on third-line antiretroviral therapy in programmatic conditions

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