RESUMEN
Zidovudine monotherapy is used to reduce perinatal HIV transmission in women with low viral loads. There are few data on the risk of drug resistance in this select cohort of women. We determined the prevalence of newly acquired mutations conferring reduced sensitivity to zidovudine after exposure during pregnancy, and found that the development of mutations was uncommon and was restricted to women treated before 1998 who had higher baseline viral loads than those currently recommended monotherapy.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/transmisión , VIH-1/genética , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Zidovudina/uso terapéutico , Estudios de Cohortes , Farmacorresistencia Viral , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Transcriptasa Inversa del VIH/genética , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Mutación/genética , Embarazo , Carga ViralRESUMEN
High levels of HIV-1 replication occur following perinatal infection and antiretroviral drugs may not fully suppress viral load during the early years of childhood. Adherence to treatment may also be difficult among children. These two factors will contribute to development of drug resistance but limited paediatric data are available. This study has, therefore, evaluated the prevalence of drug resistance among children and assessed the contribution of adherence to failing therapy. Samples from 26 children who had experienced virological failure to antiretroviral therapy were tested for drug resistance using the Visible Genetics TRUGENE trade mark HIV-1 genotyping assay. HIV-1 subtype was determined using a peptide-based EIA and drug adherence determined by physician assessment. Twenty-four children were black African, 23 of whom were infected with a non-B subtype. HIV RNA sequence data was obtained for 21 of the 26 children; at treatment failure resistance mutations were detected in the protease gene of 7 (33%) and the reverse transcriptase gene of 19 (90%). A lower proportion of children had evidence of drug resistance at nadir and no resistance mutations were detected prior to treatment. Genotypic resistance was common in those treated with lamivudine (10/11, 91%), nevirapine (6/8, 75%), and zidovudine (7/11, 64%). The prevalence of mutations was lower among those receiving other nucleoside reverse transcriptase inhibitors and protease inhibitors. In 50% of children, drug adherence was >90%. Antiretroviral drug resistance was common among this group of children failing therapy, the majority of whom were infected with non-B subtypes of HIV-1. As adherence to treatment was low in 50%, this was likely to be an important contributory factor.