Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis.

Abstract

In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented. Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%. The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.