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.

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 We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs.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

The missed HIV-positive children of Ethiopia.

OBJECTIVE: As elsewhere, due to scarcity of data and limited awareness of HIV infection, especially in older children, the HIV epidemic among Ethiopian children appears neglected in national programs (children ART coverage is of only 12% in 2013). This paper estimates the country burden of HIV in older children and investigates the prevalence of HIV in orphans and vulnerable children (OVC) households. DESIGN/METHODS: We analyzed national HIV data for Ethiopia, using Spectrum/ Estimation and Projection Package (EPP) and primary data on children living in households with at least one HIV-positive adult in the Amhara and Tigrai regions. Descriptive analysis of the age and sex distribution of HIV-positive OVC in Ethiopia was performed. RESULTS: Our Spectrum/EPP analysis estimated the population of HIV-positive children under 15 years old to be 160,000 in 2013. The majority of children (81•6%) were aged five to 14 years. The estimated number of orphans due to AIDS was 800,000. The empirical data from almost 10,000 OVC under 18 years showed 11•9% were HIV-positive, the majority of whom were between five and 10 years old with no significant difference between males and females. CONCLUSIONS: There is a large population of children living with HIV in Ethiopia, the magnitude of which not previously recognized. The majority were vertically infected and never identified nor linked into treatment. OVC represent a reachable group which could account for a substantial proportion of the HIV infected older children. We recommend that HIV programs urgently synergize with social protection sectors and address these children with HIV testing and related services.