HIV-1 drug resistance genotypic profiles in children with undetectable plasma viremia during antiretroviral therapy

Abstract

Treatment of HIV-1 infection with highly active antiretroviral therapy has led to sustained viral suppression in the plasma in a large number of children. However, studies have suggested that the integrated provirus in resting CD4+ T lymphocytes could be a source of reactivatable virus and maintain drug-resistant virus. We evaluated the resistance-related mutations in children receiving antiretroviral therapy with prolonged viral suppression. Thirty-two peripheral blood mononuclear cell samples from 16 children with viral loads that had been below detection limits for at least 12 months were obtained at two different time points and the DNAs sequenced. The median CD4 cell count was 1,016 cells/ mm 3 (347-2,588) and 938 cells/mm 3 (440-3,038) at the fi rst and second time points, respectively. The median follow-up time was 15 months (9-27). Six (37.5%) and seven (43.75%) of the 16 patients showed at least one NRTI-associated mutation in the fi rst and second samples, respectively. Two out of 16 (12.5%) had an NNRTI-associated mutation at the fi rst time point and three out of 16 (18.75%) at the second. In addition, 14 out of 16 (87.5%) had at least one PI-associated mutation at both time points. Despite plasma HIV-1 RNA suppression for at least 12 months, resistance-related mutations from previous antiretroviral failures could still be detected in archival virus. Furthermore, viral evolution occurred at the reverse transcriptase region in spite of viral suppression to levels below 400 copies/ mL. Persistence of archival resistant virus may be relevant when considering future treatment options.

HIV‐1 subtypes and drug resistance in children during antiretroviral therapy in Brazil

“…The prevalence of drug resistance mutations in children undergoing ART has been estimated to be 0 %–2.84% of drug resistance mutations 1–3 . However, Ferreira et al 4 reported a high frequency of TRDM (9.8%), and Angelis et al 5 detected high levels of antiretroviral resistance in children undergoing treatment. The only study in the North region, which was conducted in Amazonas, revealed a high rate of TDR in ART‐naïve children (16.2%), with higher levels of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) with the highest prevalence of subtype B (80%), followed by subtypes C (6%) and F (3.4%) 6 .…”