Gregson, John, Tang, Michele, Ndembi, Nicaise, Hamers, Raph L., Rhee, Soo-Yon ORCID: 0000-0002-1231-6542, Marconi, Vincent C., Diero, Lameck, Brooks, Katherine, Theys, Kristof, de Wit, Tobias F. Rinke, Arruda, Monica, Garcia, Frederico, Monge, Susana, Gunthard, Huldrych F., Hoffmann, Christopher J., Kanki, Phyllis J., Kumarasamy, Nagalingeshwaran, Kerschberger, Bernard, Mor, Orna, Charpentier, Charlotte, Todesco, Eva, Rokx, Casper, Gras, Luuk, Halvas, Elias K., Sunpath, Henry, Di Carlo, Domenico ORCID: 0000-0002-8324-4873, Antinori, Antonio, Andreoni, Massimo, Latini, Alessandra ORCID: 0000-0002-9421-6560, Mussini, Cristina, Aghokeng, Avelin, Sonnerborg, Anders ORCID: 0000-0001-8928-3374, Neogi, Ujjwal ORCID: 0000-0002-0844-3338, Fessel, William J., Agolory, Simon, Yang, Chunfu, Blanco, Jose L., Juma, James M., Smit, Erasmus, Schmidt, Daniel, Watera, Christine, Asio, Juliet, Kirungi, Wilford, Tostevin, Anna, El-Hay, Tal, Clumeck, Nathan, Goedhals, Dominique, van Vuuren, Cloete ORCID: 0000-0002-9095-0039, Bester, Philip Armand, Sabin, Caroline ORCID: 0000-0001-5173-2760, Mukui, Irene ORCID: 0000-0002-3699-1841, Santoro, Maria M., Perno, Carlo F., Hunt, Gillian, Morris, Lynn ORCID: 0000-0003-3961-7828, Camacho, Ricardo, de Oliveira, Tulio, Pillay, Deenan, Schulter, Eugene, Murakami-Ogasawara, Akio, Reyes-Teran, Gustavo, Romero, Karla, Avila-Rios, Santiago, Sirivichayakul, Sunee, Ruxrungtham, Kiat, Mekprasan, Suwanna, Dunn, David ORCID: 0000-0003-1836-4446, Kaleebu, Pontiano, Raizes, Elliot, Kantor, Rami, Shafer, Robert W. and Gupta, Ravindra K. (2016). Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study. Lancet Infect. Dis., 16 (5). S. 565 - 576. OXFORD: ELSEVIER SCI LTD. ISSN 1474-4457

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Abstract

Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per mu L). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]). Interpretation We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial. Copyright (C) The TenoRes Study Group. Open Access article distributed under the terms of CC BY.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gregson, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, MicheleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ndembi, NicaiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamers, Raph L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rhee, Soo-YonUNSPECIFIEDorcid.org/0000-0002-1231-6542UNSPECIFIED
Marconi, Vincent C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diero, LameckUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks, KatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theys, KristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Wit, Tobias F. RinkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arruda, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia, FredericoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monge, SusanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gunthard, Huldrych F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, Christopher J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kanki, Phyllis J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kumarasamy, NagalingeshwaranUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerschberger, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mor, OrnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Charpentier, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Todesco, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rokx, CasperUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gras, LuukUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halvas, Elias K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sunpath, HenryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Carlo, DomenicoUNSPECIFIEDorcid.org/0000-0002-8324-4873UNSPECIFIED
Antinori, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andreoni, MassimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Latini, AlessandraUNSPECIFIEDorcid.org/0000-0002-9421-6560UNSPECIFIED
Mussini, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aghokeng, AvelinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sonnerborg, AndersUNSPECIFIEDorcid.org/0000-0001-8928-3374UNSPECIFIED
Neogi, UjjwalUNSPECIFIEDorcid.org/0000-0002-0844-3338UNSPECIFIED
Fessel, William J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agolory, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, ChunfuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanco, Jose L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juma, James M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smit, ErasmusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Watera, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Asio, JulietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirungi, WilfordUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tostevin, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Hay, TalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clumeck, NathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goedhals, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Vuuren, CloeteUNSPECIFIEDorcid.org/0000-0002-9095-0039UNSPECIFIED
Bester, Philip ArmandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabin, CarolineUNSPECIFIEDorcid.org/0000-0001-5173-2760UNSPECIFIED
Mukui, IreneUNSPECIFIEDorcid.org/0000-0002-3699-1841UNSPECIFIED
Santoro, Maria M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perno, Carlo F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunt, GillianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris, LynnUNSPECIFIEDorcid.org/0000-0003-3961-7828UNSPECIFIED
Camacho, RicardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Oliveira, TulioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pillay, DeenanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulter, EugeneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murakami-Ogasawara, AkioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reyes-Teran, GustavoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romero, KarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Avila-Rios, SantiagoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sirivichayakul, SuneeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruxrungtham, KiatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mekprasan, SuwannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunn, DavidUNSPECIFIEDorcid.org/0000-0003-1836-4446UNSPECIFIED
Kaleebu, PontianoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raizes, ElliotUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kantor, RamiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shafer, Robert W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gupta, Ravindra K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-277969
DOI: 10.1016/S1473-3099(15)00536-8
Journal or Publication Title: Lancet Infect. Dis.
Volume: 16
Number: 5
Page Range: S. 565 - 576
Date: 2016
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1474-4457
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TENOFOVIR DISOPROXIL FUMARATE; IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL THERAPY; VIROLOGICAL FAILURE; HIV-1-INFECTED PATIENTS; NAIVE PATIENTS; SUBTYPE C; EFAVIRENZ; EMTRICITABINE; LAMIVUDINEMultiple languages
Infectious DiseasesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27796

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