HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral treatment in KwaZulu-Natal Province, South Africa.

BACKGROUND In low- and middle-income countries, increasing levels of HIV drug resistance (HIVDR) on second-line protease inhibitor (PI)-based regimens are a cause for concern, given limited drug options for third-line antiretroviral therapy (ART). OBJECTIVES We conducted a retrospective analysis of routine HIV-1 genotyping laboratory data from KwaZulu-Natal, in South Africa, to describe the frequency and patterns of HIVDR mutations and their consequent impact on standardized third-line regimens. METHODS This was a cross-sectional analysis of all HIV-1 genotypic resistance tests conducted by the National Health Laboratory Service in KwaZulu-Natal, South Africa (Jan 2015 - Dec 2016), for adults and adolescents (age ≥10 years) on second-line PI-based ART with virological failure. We assigned a third-line regimen to each record, based on a national treatment algorithm and calculated the genotypic susceptibility score (GSS) for that regimen. RESULTS Of 348 samples analyzed, 287 (83%) had at least one drug resistance mutation (DRM) and 114 (33%) had at least one major PI DRM. Major PI resistance was associated with longer duration on second-line ART (aOR per 6-months, 1.11, 95% CI 1.04-1.19) and older age (aOR 1.03, 95% CI 1.01-1.05). Of 112 patients requiring third-line ART, 12 (11%) had a GSS of <2 for the algorithm-assigned third-line regimen. CONCLUSIONS One in three people failing second-line ART had significant PI DRMs. A subgroup of these individuals had extensive HIVDR, where the predicted activity of third-line ART was suboptimal, highlighting the need for continuous evaluation of outcomes on third-line regimens and close monitoring for emergent HIV-1 integrase-inhibitor resistance.