Pharmaco-virological Outcomes and Genotypic Resistance Profiles Among Children and Adolescents Receiving a Dolutegravir (DTG)-Based Regimen in Togo

Abstract

Abstract Background Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (-DTG) as human immunodeficiencyvirus (HIV) treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents. Methods A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-generation sequencing of protease, reverse transcriptase (RT), and integrase was performed on all samples with viral loads >200 copies/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm. Results 264 participants were enrolled (median age, 17 years); 226 received a DTG-based regimen for a median of 20.5 months. Among them, there was virological suppression at the 200-copies/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (ie, >640 ng/mL), suboptimal, and below the limit of quantification in 74.1%, 6.7%, and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of nucleoside RT inhibitors, non-NRTIs, and protease inhibitors were found in 52%, 66%, and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n = 3/32; R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 copies/mL. Conclusions These first findings in a large series of adolescents in a low-income country showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.