RESUMO
OBJECTIVES: Single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of HIV-1 results in the selection of genotypic drug resistance mutations. To assess the levels of phenotypic resistance conferred by these mutations, we examined the ability of sample-derived HIV-1 reverse transcriptase to function in the presence of nevirapine (NVP). METHODS: Plasma samples from HIV-1 pregnant women before and after exposure to sdNVP were used to extract viral reverse transcriptase for the Cavidi ExaVir Drug susceptibility assay. The fold increases in phenotypic resistance for each sample were compared with the genotypic profiles determined by population-based sequencing. RESULTS: None of the women sampled before sdNVP exposure had phenotypic resistance (median fold increase 0.7). Seven weeks after sdNVP, there was a 16-fold increase in phenotypic resistance among women who had NVP resistance mutations compared with only a 1.9-fold increase among NVP-exposed women with wild-type virus. Phenotypic resistance decayed with time coincident with the fading of genotypic mutations, and by 18 months, all samples were phenotypically susceptible. CONCLUSIONS: Exposure of pregnant women to sdNVP was associated with the transient appearance of viral populations that displayed phenotypic resistance to NVP. Overall, there was good concordance between phenotypic resistance to NVP, as measured with this enzymatic assay, and the presence of NVP genotypic mutations.
Assuntos
Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/administração & dosagem , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Esquema de Medicação , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/transmissão , Infecções por HIV/virologia , Transcriptase Reversa do HIV/metabolismo , HIV-1/classificação , HIV-1/genética , Humanos , Lactente , Nevirapina/farmacologia , Nevirapina/uso terapêutico , Fenótipo , GravidezRESUMO
Nevirapine used in single doses to prevent mother-to-child transmission has been shown to be associated with the development of transient resistant mutations. Here we describe the presence of V106M in seven out of 141 South African women (5%) 6 weeks after receiving nevirapine. V106M is a novel resistance mutation found in subtype C viruses exposed to efavirenz. This mutation is thus also induced at a low frequency in subtype C viruses exposed to single dose nevirapine.
