Drug Resistance Among Newly Diagnosed HIV-Infected Children in the Era of More Efficacious Antiretroviral Prophylaxis

Louise Kuhn; Gillian Hunt; Karl-Günter Technau; Ashraf Coovadia; Johanna Ledwaba; Sam Pickerill; Martina Penazzato; Silvia Bertagnolio; Claude A. Mellins; Vivian Black; Lynn Morris; Elaine J. Abrams

Disclosures

AIDS. 2014;28(11):1673-1678. 

In This Article

Abstract and Introduction

Abstract

Background. 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.

Methods. 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.

Results. 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%.

Conclusion. 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.

Introduction

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are still recommended as part of prevention of mother-to-child transmission (PMTCT) regimens, including option B/B+, despite the well described selection of resistance mutations among a large proportion of PMTCT-exposed women and their infected infants.[1,2] However, these data come predominantly from clinical trials and research cohorts and the frequency of prophylaxis-selected drug resistance in routine programs is less well established.[3]

Although PMTCT dramatically reduces the risk of pediatric HIV infection, it does not entirely prevent transmission.[4] Infants with no PMTCT exposure are at higher risk of infection than PMTCT-exposed infants, but the proportion exposed is a function of population coverage of PMTCT. In many settings, ritonavir-boosted lopinavir (LPV/r)-based regimens are only recommended for infants with reported PMTCT exposure on the assumption that NNRTI-associated mutations rarely occur outside this group. However, the prevalence and patterns of drug resistance in HIV-infected infants with no reported history of PMTCT have not been described.

Our study was designed to describe drug resistance among newly diagnosed, treatment-naive, HIV-infected children under 2 years of age accessing routine services in Johannesburg, South Africa, a year after PMTCT guidelines were changed to support more effective interventions, including wider use of maternal combination antiretroviral therapy (cART).[5,6]

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