Author(s): ElKhatib Z, Delong AK, Katzenstein D, Ekstrom AM, Ledwaba J,
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Abstract BACKGROUND: Emergence of HIV-1 drug resistance is at times an inevitable and anticipated consequence of antiretroviral therapy (ART) failure. We examined drug resistance patterns and virus re-suppression among subtype C-infected South African patients receiving first-line ART. METHODS: Treatment records of 431 patients on NNRTI-containing regimens for a median of 45 months were analyzed. Patients with viral load (VL) >400 copies/mL were followed and drug resistance mutations (DRM) were re-assessed. Associations between clinical/demographic measures and drug resistance/virologic outcomes were examined using Fisher exact and ordinal and logistic regression. RESULTS: Ten percent of patients (43/431) were viremic at enrollment (98\% previously suppressed); sequences were obtained from 38/43. Of those, 82\% had 1-7 DRM. In bivariate analysis remote exposure to single-dose nevirapine or prior ART; higher CD4 counts; lower VL; and >6 months of virologic failure were significantly associated with number of DRM. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48\%) re-suppressed, six with K103N and three with M184V. Thirteen (52\%) had continued virologic failure which was significantly associated with detectable VL>6 months prior to enrollment and number of DRM. CONCLUSION: Among these HIV-1 subtype C-infected patients, DRM numbers and patterns were associated with prior exposure to sub-optimal ART, adherence and duration of virologic failure. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. In resource-limited settings, where genotyping and alternative drug options are unavailable, continuing first-line treatment, reinforcing adherence and regular virologic monitoring may be effective even after virologic failure.
This article was published in J AIDS Clin Res
and referenced in Journal of Clinical & Cellular Immunology