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Lancet Infect Dis. 2018 Mar;18(3):346-355. doi: 10.1016/S1473-3099(17)30702-8. Epub 2017 Dec 5.

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.

Author information

1
Department of Infection, University College London, London, UK; Africa Health Research Institute, Durban, South Africa. Electronic address: ravindra.gupta@ucl.ac.uk.
2
Department of Statistics, London School of Hygiene & Tropical Medicine, London, UK.
3
Data First Consulting, Belmont, CA, USA.
4
HIV Department, World Health Organization, Geneva, Switzerland.
5
Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
6
Ministry of Health, Bogotá, Columbia.
7
Uganda Virus Research, Entebbe, Uganda; Medical Research Council and Uganda Virus Research Institute, Uganda Research Unit, Entebbe, Uganda.
8
CREMER, Virology laboratory IMPM-IRD, IMPM, Yaoundé, Cameroon; IRD UMI 233, INSERM U1175, Université de Montpellier, Montpellier, France.
9
Ministry of Health, Windhoek, Namibia.
10
Ministry of Health and Child Care, Harare, Zimbabwe.
11
Department of Public Health, Ministry of Health and Sports, Yangoon, Myanmar.
12
Department of Epidemiology, Guatemala City, Guatemala.
13
HIV Program, Ministry of Health, Guatemala City, Guatemala.
14
HIV Reference Laboratory, Guatemala City, Guatemala.
15
Ministry of Health, Managua, Nicaragua.
16
Universidad del Valle de Guatemala Centro de Estudios en Salud, Guatemala City, Guatemala.
17
Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands; Department of Global Health, Academic Medical Centre of the University of Amsterdam, Amsterdam, Netherlands.
18
Laboratory Medicine, Global Health and Medicine, University of Washington, Seattle, WA, USA; Seattle Children's Research Institute, Seattle, WA, USA.
19
Departments of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, WA, USA.
20
KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
21
Department of Infection, University College London, London, UK; Africa Health Research Institute, Durban, South Africa.
22
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
23
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
24
Department of Infection, University College London Hospital, London, UK.
25
National Institute for Communicable Diseases, Sandringham, South Africa.
26
Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
27
Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; Division of Geographic Medicine and Infectious Disease, Tufts Medical Center, Boston, MA, USA.

Erratum in

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.

FUNDING:

Bill & Melinda Gates Foundation and World Health Organization.

Comment in

PMID:
29198909
PMCID:
PMC5835664
DOI:
10.1016/S1473-3099(17)30702-8
[Indexed for MEDLINE]
Free PMC Article

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