Abstract
SummaryBackgroundPretreatment 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.MethodsThis 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 We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs.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.FindingsWe 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.InterpretationPretreatment 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.FundingBill & Melinda Gates Foundation and World Health Organization.
Highlights
Implications of all the available evidence Our results show that some low-income and middle-income countries (LMICs) might be reaching WHO’s 10% threshold for changing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) to integrase inhibitor-based ART
We detected an association between men who have sex with men and overall HIV drug resistance in Asia (p=0·047), but not for NNRTI or nucleoside reverse transcriptase inhibitors (NRTIs) resistance or in other geographical regions
WHO 2016 antiretroviral guidelines recommend the use of NNRTI as a component of first-line ART regimens,[4] which is widely implemented in LMICs, irrespective of previous exposure to antiretroviral drugs
Summary
We aimed to assess the scale of this problem and whether it is associated with the intiation November 30, 2017 or re-initiation of ART in people who have had previous exposure to antiretroviral drugs
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