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

• Published in: Journal of antimicrobial chemotherapy Vol. 78; no. 8; pp. 2000 - 2007
• Main 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, Kemp, Steven A, Gupta, Ravindra K
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 02-08-2023
• Subjects: Adult; Cross-Sectional Studies; Drug Resistance, Viral - genetics; Heterocyclic Compounds, 3-Ring - pharmacology; Heterocyclic Compounds, 3-Ring - therapeutic use; HIV Infections - drug therapy; HIV Integrase Inhibitors - pharmacology; HIV Integrase Inhibitors - therapeutic use; Humans; Integrases - genetics; Mutation; Original Research; Oxazines - therapeutic use; Pyridones - therapeutic use
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkad195

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.