Varied Patterns of HIV-1 Drug Resistance on Failing First-Line Antiretroviral Therapy in South Africa

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Abstract

Background:

The South African national antiretroviral therapy roll-out program is entering its sixth year, with over 570,000 adults accessing treatment. HIV-1 drug resistance is a potential consequence of therapy. This study determined the pattern of HIV-1 drug resistance mutations after failure of first-line treatment regimens in South Africa.

Methods:

Two hundred and twenty-six patients virologically failing first-line regimens were studied to determine resistance patterns.

Results:

The most common reverse transcriptase mutation was M184V/I (72%; n = 163); 11% of patients (n = 25) had only nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations and 17% (n = 38) had no known resistance mutations. The K65R mutation was detected in 4%. The frequency of thymidine analog mutations was significantly higher with azidothymidine-containing (31 of 57) than stavudine-containing regimens (39 of 169; P < 0.001). The Y181C mutation was more frequent with failure of nevirapine (NVP)-containing (26%) than efavirenz (EFV)-containing therapy (3%; P < 0.001). The V106M mutation was more frequent with EFV (30%) than NVP (4%; P = 0.012).

Conclusions:

HIV-1 drug resistance patterns varied broadly after failure of first-line therapy, ranging from no known resistance mutations (17%) to multinucleoside reverse transcriptase inhibitor and NNRTI resistance (23%). NNRTI mutation profiles differed for patients on EFV- compared with NVP-containing regimens. Overall, these findings suggest that HIV-1 drug resistance testing would be useful in identifying most appropriate second-line regimens.

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