HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST).

Autor:	Egger M; Institute of Social & Preventive Medicine, University of Bern, Bern, Switzerland matthias.egger@ispm.unibe.ch.; Centre for Infectious Disease Epidemiology and Research, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa., Sauermann M; Institute of Social & Preventive Medicine, University of Bern, Bern, Switzerland., 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 & Preventive Medicine, University of Bern, Bern, Switzerland., Riedo S; Institute of Social & Preventive Medicine, University of Bern, Bern, Switzerland., Beerenwinkel N; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland., Jaquet A; National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Bordeaux, France., Minga A; Centre Médical de Suivi des Donneurs de Sang, Abidjan, Côte d'Ivoire., Ross J; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand., Giandhari J; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), University of KwaZulu-Natal, Durban, South Africa., Kouyos RD; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.; Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Lessells R; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), University of KwaZulu-Natal, Durban, South Africa.; Centre for the Aids Programme of Research in South Africa (CAPRISA), Durban, South Africa.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2024 Aug 21; Vol. 14 (8), pp. e085819. Date of Electronic Publication: 2024 Aug 21.
DOI:	10.1136/bmjopen-2024-085819
Abstrakt:	Introduction: HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the WHO in 2019 for first-line, second-line and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance. Methods and Analysis: Nested within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST is a multicentre study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virological failure on dolutegravir-based ART. At the time of virological failure, whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (1) individuals who experienced virological failure on dolutegravir and (2) those who started or switched to such a regimen and were at risk of virological failure. For population (1), the outcome will be any InSTI drug resistance mutations, and for population (2) virological failure is defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virological failure and limited power for analysing factors associated with individual InSTI drug resistance mutations. Ethics and Dissemination: The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in International epidemiology Databases to Evaluate AIDS and have obtained ethics approval from their local ethics committee to collect additional data. Trial Registration Number: NCT06285110. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
Databáze:	MEDLINE
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