Title: HIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies
Authors: Loosli T, Hossmann S, Ingle SM, Okhai H, Kusejko K, Mouton J, Bellecave P, van Sighem A, Stecher M, Monforte AD, Gill MJ, Sabin CA, Maartens G, GÃÂ¼nthard HF, Sterne JAC, Lessells R, Egger M, Kouyos R.
Journal: medRxiv,5:2023.04.05.23288183. doi: 10.1101/2023.04.05.23288183: (2023)
Background: The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) in first- and second-line antiretroviral therapy (ART) may facilitate emerging resistance. We combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for DTG resistance.
Methods: Eight cohorts from Canada, Europe, and South Africa contributed data on individuals with genotypic resistance testing on DTG-based ART. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models.
Results: We included 750 people with genotypic resistance testing on DTG-based ART between 2013 and 2022. Most had HIV subtype B (N=444, 59Â·2%) and were treatment-experienced; 134 (17.9%) were on DTG dual and 19 (2.5%) on DTG monotherapy. INSTI DRMs were detected in 100 (13Â·3%) individuals; 21 (2Â·8%) had more than one mutation. Most (N=713, 95Â·1%) were susceptible to DTG, 8 (1Â·1%) had potential-low, 5 (0Â·7%) low, 18 (2Â·4%) intermediate and 6 (0Â·8%) high-level DTG resistance. The risk of DTG resistance was higher on DTG monotherapy (adjusted odds ratio (aOR) 37Â·25, 95% CI 11Â·17 to 124Â·2) and DTG lamivudine dual therapy (aOR 6Â·59, 95% CI 1Â·70 to 25Â·55) compared to combination ART, and higher in the presence of potential-low/low (aOR 4.62, 95% CI 1.24 to 17.2) or intermediate/high-level (aOR 7Â·01, 95% CI 2Â·52 to 19Â·48) nucleoside reverse transcriptase inhibitors (NRTI) resistance. Viral load on DTG showed a trend towards increased DTG resistance (aOR 1Â·42, 95% CI 0Â·92 to 2Â·19 per standard deviation of log 10 area under the viral load curve).
Interpretation: Among people experiencing virological failure on DTG-based ART, INSTI DRMs were uncommon, and DTG resistance was rare. DTG monotherapy and NRTI resistance substantially increased the risk for DTG resistance, which is of concern, notably in resource-limited settings.
Download: Full text paper
Citation: Loosli T, Hossmann S, Ingle SM, Okhai H, Kusejko K, Mouton J, Bellecave P, van Sighem A, Stecher M, Monforte AD, Gill MJ, Sabin CA, Maartens G, GÃ¼nthard HF, Sterne JAC, Lessells R, Egger M, Kouyos R. HIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies medRxiv,5:2023.04.05.23288183. doi: 10.1101/2023.04.05.23288183: (2023).