Author(s): Orrell C, Walensky RP, Losina E, Pitt J, Freedberg KA, , Orrell C, Walensky RP, Losina E, Pitt J, Freedberg KA,
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Abstract BACKGROUND: This study aimed to evaluate HIV type-1 (HIV-1) drug resistance pretreatment and in those failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in South Africa. METHODS: This was an observational cohort. Genotypic resistance testing was performed on treatment-naive individuals and those failing first-line ART (confirmed HIV-1 RNA>1,000 copies/ml) from public sector clinics in Cape Town (2002-2007). Resistance profiles and mutations relative to timing of known virological failure were examined. RESULTS: In total, 230 patients (120 treatment-naive and 110 with virological failure) were included: 98\% had clade C virus. Among treatment-naive patients, prevalence of primary resistance was 2.5\% (95\% confidence interval 0.0-5.3). Three patients had one significant reverse transcriptase mutation: K65R, Y181C and G190A. Among treatment-experienced patients, 95 (86\%) individuals had therapy-limiting NNRTI mutations, including K103N (55\%), V106M (31\%) and Y181C (9\%). The M184V mutation was the most common mutation, found in 86 (78\%) patients. In total, 10 (9\%) patients had the K65R mutation. More individuals tended to develop thymidine analogue mutations when sampling occurred after 6 months of detected therapy failure (10/31 [32\%] individuals) compared with those who had genotyping before 6 months (15/79 [19\%] patients; P=0.246). CONCLUSIONS: Prevalence of primary resistance in a sample of ART-naive clade C HIV-1-infected individuals in South Africa was low during the study period. Patients failing first-line ART most often developed resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, the two drug classes used in first-line therapy. Viral load monitoring in this setting is crucial and individual genotypes in those failing first-line therapy should be considered.
This article was published in Antivir Ther
and referenced in Journal of AIDS & Clinical Research