HIV Drug Resistance Patterns at the Epicentre of the HIV-1 Epidemic in Kwazulu-Natal, South Africa 2003-2013

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South Africa has the highest number of individuals with HIV-1 infection worldwide with the epicentre of the epidemic in the province of KwaZulu-Natal (KZN). Currently South Africa has the largest antiretroviral treatment (ART) programme with KZN and Gauteng provinces accounting for 56% of all patients on ART. In order to understand transmission dynamics and temporal trends in drug resistance, we performed a comprehensive literature review of primary and acquired drug resistance in adults and children in KZN over a ten year period, 2003-2013. Transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in adults is increasing to moderate levels (5-15%). Acquired drug resistance to first line drug regimens in adults was associated with at least one mutation to nucleoside reverse transcriptase inhibitors (NRTI) or NNRTIs or both, with M184V and K103N the most common mutations. Prevalence of thymidine analogues (TAMs) was low to moderate. There was no published data on acquired drug resistance to second line agents. Children failing first line drug regimens harboured drug resistance mutations to NRTI (M184V and TAMs), NNRTI (V106M and K103N) and protease inhibitors (PIs) (V82A). Concerns have been raised about the high levels of the K65R mutation associated with tenofovir regimens in adults and children. Continued vigilance is needed for ART failure in both adults and children, so as not to compromise second line treatment options. Drug resistance genotyping is now cost effective and should be considered for inclusion in regional surveillance studies and during routine care.