HIV-1 drug resistance in adults and adolescents on protease inhibitor-based antiretroviral treatment in KwaZulu-Natal Province, South Africa.
Chimukangara B., Lessells RJ., Sartorius B., Gounder L., Manyana S., Pillay M., Singh L., Giandhari J., Govender K., Samuel R., Msomi N., Naidoo K., de Oliveira T., Moodley P., Parboosing R.
BackgroundIn 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).ObjectivesWe 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.MethodsThis 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.ResultsOf 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.ConclusionsOne 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.