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

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 We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs.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.

Evolution of transmitted HIV‐1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

“…Different patterns of TDR in non‐Italian‐born individuals reflect the situation of global resistance emergence in the different geographical areas. We observed a higher prevalence of NNRTI resistance in those originating from sub‐Saharan Africa, while NRTI resistance was more frequent in those originating from Latin America, reflecting the prevalence of pre‐ART resistance reported in local studies . Unlike other reports of higher TDR among men who have sex with men (MSM) , in our cohort the prevalence of any TDR was slightly although not significantly higher among injecting drug users, which could be explained by HIV transmission from contacts treated during earlier years of the epidemics with less effective drugs .…”

Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root

“…However, long-term widespread use of HAART can lead to drugresistant viruses and treatment failure [7]. At least 50% of patients have drug-resistant viruses.…”

Discovery of potent HIV‐1 non‐nucleoside reverse transcriptase inhibitors by exploring the structure–activity relationship of solvent‐exposed regions I

“…Currently, there are five FDAapproved NNRTIs administered as a combination therapy in HAART, including the first generation NNRTIs nevirapine (NVP), efavirenz (EFV), delavirdine (DLV) and the secondgeneration NNRTIs etravirine (ETV, 1) and rilpivirine (RPV, 2; Chen, Zhan, Li, De Clercq, & Liu, 2011;De Clercq & Li, 2016; Figure 1). Although HAART has greatly reduced the morbidity and mortality of AIDS, the increasing incidence of drug resistant continues being a major cause of treatment failure (Gupta et al, 2017). Among all the mutant strains, K103N and Y181C are the two most prevalent mutations selected by NVP and EFV (Johnson et al, 2005), E138K are the mutant strains most frequently selected by RPV (Bec et al, 2013).…”