sHIV-1 drug resistance in people on dolutegravir-based ART: Collaborative analysis of cohort studies.

Autor: Loosli T; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Hossmann S; Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland., Ingle SM; Population Health Sciences, Bristol Medical School, University of Bristol, UK., Okhai H; Institute for Global Health, University College London, UK., Kusejko K; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Mouton J; Department of Medicine, University of Cape Town, Cape Town, South Africa., Bellecave P; Virology laboratory, University Hospital Bordeaux, Bordeaux, France., van Sighem A; Stichting hiv monitoring, Amsterdam, the Netherlands., Stecher M; German Center for Infection Research (DZIF), Partner-Site Cologne-Bonn, Cologne, Germany.; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf., d'Arminio Monforte A; Italian Cohort Naive Antiretrovirals, (ICONA) L'Azienda Socio Sanitaria Territoriale (ASST) Santi Paolo e Carlo, Milano, Italy., Gill MJ; Southern Alberta Clinic, Calgary, AB, Canada.; Department of Medicine, University of Calgary, Calgary, AB, Canada., Sabin CA; Institute for Global Health, University College London, UK., Maartens G; Department of Medicine, University of Cape Town, Cape Town, South Africa., Günthard HF; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Sterne JAC; Population Health Sciences, Bristol Medical School, University of Bristol, UK., Lessells R; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.; Centre for Infectious Disease Epidemiology and Research, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Egger M; Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.; Population Health Sciences, Bristol Medical School, University of Bristol, UK.; Centre for Infectious Disease Epidemiology and Research, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Kouyos R; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2023 Apr 05. Date of Electronic Publication: 2023 Apr 05.
DOI: 10.1101/2023.04.05.23288183
Abstrakt: 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, 59·2%) and were treatment-experienced; 134 (17.9%) were on DTG dual and 19 (2.5%) on DTG monotherapy. INSTI DRMs were detected in 100 (13·3%) individuals; 21 (2·8%) had more than one mutation. Most (N=713, 95·1%) were susceptible to DTG, 8 (1·1%) had potential-low, 5 (0·7%) low, 18 (2·4%) intermediate and 6 (0·8%) high-level DTG resistance. The risk of DTG resistance was higher on DTG monotherapy (adjusted odds ratio (aOR) 37·25, 95% CI 11·17 to 124·2) and DTG lamivudine dual therapy (aOR 6·59, 95% CI 1·70 to 25·55) 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 7·01, 95% CI 2·52 to 19·48) nucleoside reverse transcriptase inhibitors (NRTI) resistance. Viral load on DTG showed a trend towards increased DTG resistance (aOR 1·42, 95% CI 0·92 to 2·19 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.
Competing Interests: SMI reports grant funding from NIH NIAAA for the work of ART-CC (payment to institution). AvS reports funding from the Dutch Ministry of Health, Welfare and Sport for the maintenance of the ATHENA database, and grant funding from the European Centre for Disease Prevention and Control (ECDC) (payment to institution). MJG reports honoraria as Ad Hoc member of HIV National Advisory Board from Merck, Gilead Sciences, and ViiV, and a leadership position as Medical Director S Alberta HIV clinic. CAS has received funding from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for membership of Data Safety and Monitoring Committees, Advisory Committees and for preparation of educational material. HFG has received personal fees from Merck, Gilead Sciences, ViiV, GSK, Janssen, Johnson and Johnson and Novartis, as an advisor/consultant or for DSMB membership and has received a travel grant from Gilead. JACS reports funding for research in this publication from NIH NIAAA (payment to institution), UK NIHR (payment to institution), and the University of Bern (payment to institution). RL reports support for research in this publication by the National Institute of Allergy & Infectious Diseases of the National Institutes of Health under award number R01AI152772, and support from the National Institute of Allergy & Infectious Diseases of the National Institutes of Health under award number R01AI167699 for a separate project pertaining to HIV treatment strategies. ME reports funding for research in this publication from the Swiss National Science Foundation (32FP30-18949) and the National Institutes of Health (Cooperative Agreement AI069924 and R01 AI152772-01). RK reports funding for research in this publication from the Swiss National Science Foundation and the National Institute of Allergy & Infectious Diseases of the National Institutes of Health, and reports grant funding from Gilead Sciences. All other authors declare no competing interest.
Databáze: MEDLINE
Externí odkaz: