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
Adam Abdullahi, Ibrahim Musa Kida, Umar Abdullahi Maina, Amina Husaini Ibrahim, James Mshelia, Haruna Wisso, Abdullahi Adamu, James Onyemata, Martin Edun, Haruna Yusuph, Sani Aliyu, Manhattan Charurat, Alash’le Abimiku, Lucie Abeler‐Dörner, Christophe Fraser, David Bonsall, Lucie Abeler‐Dörner, Helen Ayles, David Bonsall, Rory Bowden, Vincent Cálvez, Max Essex, Sarah Fidler, Christophe Fraser, Kate Grabowski, Tanya Golubchik, Ravindra K. Gupta, Richard Hayes, Joshua T. Herbeck, Joseph Kagaayi, Pontiano Kaleebu, Jairam R. Lingappa, Sikhulile Moyo, Vladimir Novitsky, Thumbi Ndung’u, Deenan Pillay, Thomas C. Quinn, Andrew Rambaut, Oliver Ratmann, Janet Seeley, Deogratius Ssemwanga, Frank Tanser, Maria J. Wawer, Myron S. Cohen, Tulio D’Oliveira, Ann M. Dennis, Max Essex, Sarah Fidler, Dan Frampton, Christophe Fraser, Tanya Golubchik, Richard Hayes, Josh Herbeck, Anne Hoppé, Pontiano Kaleebu, Paul Kellam, Cissy Kityo, Andrew Brown, Jairam R. Lingappa, Vladimir Novitsky, Nick Paton, Deenan Pillay, Tom Quinn, Oliver Ratmann, Deogratius Ssemwanga, Frank Tanser, Maria J. Wawer, Steven A. Kemp, Ravindra K. Gupta
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.