Dynamics and drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors in nine African countries

Background. The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) is a major problem in countries of southern Africa. Understanding the dynamics and drivers of NNRTI resistance at the country level is of critical importance for planning future antiretroviral therapy (ART) programs. Methods. We collected survey data on pretreatment drug resistance (PDR) to NNRTIs in nine countries of southern Africa from 2000 to 2018. We fitted a dynamic transmission model to key indicators of the local HIV-1 epidemics (HIV-1 prevalence, ART coverage and mortality) and to survey data about NNRTI PDR using a Bayesian hierarchical framework. We estimated two country-level indicators: the proportion of NNRTI PDR that cannot be attributed to ART programmes and the vulnerability to NNRTI PDR within ART programmes. We explored associations between vulnerability to NNRTI PDR and country-level covariates.Findings. The model reliably described the dynamics of HIV-1 and the dynamics of NNRTI PDR in each country. Predicted levels of NNRTI PDR in 2018 ranged between 3.3% (95% credible interval 1.9% to 7.1%) in Mozambique and 25.3% (17.9% to 33.8%) in Eswatini. The main determinant of high NNRTI PDR were the conjunction of high ART coverage and high vulnerability to NNRTI PDR within ART programmes. Heterogeneity in the vulnerability to NNRTI resistance was associated with features of the healthcare financing system at the national level.Interpretation. Between-country comparison shows that NNRTI PDR can be controlled despite high levels of ART coverage, as in Botswana, Lesotho, Mozambique and Zambia, likely because of better adherence, patient management procedures and quality in HIV care service delivery.