Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort
Authors: Abdullahi Adam , Kida Ibrahim Musa , Maina Umar Abdullahi , Ibrahim Amina Husaini , Mshelia James , Wisso Haruna , Adamu Abdullahi , Onyemata James Ezenwa , Edun Martin , Yusuph Haruna , Aliyu Sani H , Charurat Man , Abimiku Alash’le , Abeler-Dorner Lucie , Fraser Christophe , Bonsall David ,   PANGEA consortium, Abeler-Dörner Lucie , Ayles Helen , Bonsall David , Bowden Rory , Calvez Vincent , Essex Max , Fidler Sarah , Fraser Christophe , Grabowski Kate , Golubchik Tanya , Gupta Ravindra , Hayes Richard , Herbeck Joshua , Kagaayi Joseph , Kaleebu Pontiano , Lingappa Jairam , Moyo Sikhulile , Novitsky Vladimir , Ndung'u Thumbi , Pillay Deenan , Quinn Thomas , Rambaut Andrew , Ratmann Oliver , Seeley Janet , Ssemwanga Deogratius , Tanser Frank , Wawer Maria , Cohen Myron , D'Oliveira Tulio , Dennis Ann , Essex Max , Fidler Sarah , Frampton Dan , Fraser Christophe , Golubchik Tanya , Hayes Richard , Herbeck Josh , Hoppe Anne , Kaleebu Pontiano , Kellam Paul , Kityo Cissy , Leigh-Brown Andrew , Lingappa Jairam , Novitsky Vladimir , Paton Nick , Pillay Deenan , Quinn Tom , Ratmann Oliver , Ssemwanga Deogratius , Tanser Frank , Wawer Maria , Kemp Steven A , Gupta Ravindra K 
Published: June 2023

Abstract

Background
Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa.

Aims
We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen.

Methods
WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy.

Results
Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility—this was characterized by the T66A, G118R, E138K and R263K mutations.

Conclusions
This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.