The global burden of HIV-1 drug resistance in the past 20 years.

Genotypic drug resistance testing has been an integral part of the clinical management of HIV patients for almost 20 years, not only assisting treatment choices but also informing drug development. Accurate estimations on the worldwide circulation of drug resistance are difficult to obtain, particularly in low/middle-income countries. In this work, we queried two of the largest public HIV sequence repositories in the world-Los Alamos and Stanford HIVdb-to derive global prevalence, time trends and geodemographic predictors of HIV drug resistance. Different genotypic interpretation systems were used to ascertain resistance to reverse transcriptase and protease inhibitors. Continental, subtype-specific (including circulating recombinant forms) stratification as well as analysis on drug-naïve isolates were performed. Geographic information system analysis correlated country-specific drug resistance to sociodemographic and health indicators obtained from the World Bank. By looking at over 33,000 sequences worldwide between 1996 and 2016, increasing drug resistance trends with non-B subtypes and recombinants were found; transmitted drug resistance appeared to remain stable in the last decade. While an increase in drug resistance is expected with antiretroviral therapy rollout in resource-constrained areas, the plateau effect in areas covered by the most modern drug regimens warns against the downgrading of the resistance issue.