HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

• Authors: Ravindra K. Gupta, University College London; John Gregson, London School of Hygiene & Tropical Medicine; Neil Parkin, Data First Consulting; Hiwot Haile-Selassie, World Health Organization; Amilcar Tanuri, Federal University of Rio de Janeiro; Liliana Andrade Forero, Ministry of Health Columbia; Pontiano Kaleebu, Uganda Virus Research Institute; Christine Watera, Uganda Virus Research Institute; Avelin Aghokeng, Institute for Medical Research and Studies of Medicinal Plants; Nicholus Mutenda, Ministry of Health Namibia; Janet Dzangare, Ministry of Health Zimbabwe; San Hone, Ministry of Health Myanmar; Zaw Zaw Hang, Ministry of Health Myanmar; Judith Garcia, Department of Epidemiology Guatemala; Zully Garcia, Ministry of Health Guatemala; Paola Marchorro, HIV Reference Laboratory; Enrique Beteta, Ministry of Health Nicaragua; Amalila Giron, Universidad del Valle de Guatemala Centro de Estudios en Salud; Raph Hamers, University of Amsterdam; Seth Inzaule, University of Amsterdam; Lisa M. Frenkel, University of Washington; Michael Chung, Emory University; Tulio de Oliveira, University of KwaZulu-Natal; Deenan Pillay, University College London; Kogie Naidoo, Centre for the AIDS Programme of Research in South Africa; Ayesha Kharsany, Centre for the AIDS Programme of Research in South Africa; Ruthiran Kugathasan, University College London; Teresa Cutino, University College London; Gillian Hunt, National Institute for Communicable Diseases; Santiago Avila Rios, National Institute of Respiratory Diseases; Meg Doherty, World Health Organization; Michael R. Jordan, Tufts University; Silvia Bertagnolio, World Health Organization
• Journal Title: LANCET INFECTIOUS DISEASES
• Volume: Volume 18, Number 3
• Publisher: ELSEVIER SCI LTD | 2018-03-01, Pages 346-355
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/S1473-3099(17)30702-8
• Subjects: Biology, Virology; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Infectious Diseases; SUB-SAHARAN AFRICA; VIROLOGICAL FAILURE; VIRAL FAILURE; MUTATIONS; ACCUMULATION; METAANALYSIS; INDIVIDUALS; IMPACT; COHORT; ADULTS

Abstract

Background: Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs. Methods: This study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions. Findings: We identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5–15·9) in southern Africa, 10·1% (5·1–19·4) in eastern Africa, 7·2% (2·9–16·5) in western and central Africa, and 9·4% (6·6–13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly increases in the odds of pretreatment drug resistance were 23% (95% CI 16–29) in southern Africa, 17% (5–30) in eastern Africa, 17% (6–29) in western and central Africa, 11% (5–18) in Latin America and the Caribbean, and 11% (2–20) in Asia. Estimated increases in the absolute prevalence of pretreatment drug resistance between 2015 and 2016 ranged from 0·3% in Asia to 1·8% in southern Africa. Interpretation: Pretreatment drug resistance is increasing at substantial rate in LMICs, especially in sub-Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near WHO's 10% threshold for changing first-line ART in southern and eastern Africa and Latin America, underscoring the need for routine national HIV drug-resistance surveillance and review of national policies for first-line ART regimen composition.