Abstract
BackgroundIntrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy.MethodsThis analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list.ResultsPerinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy.ConclusionsInfants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.
Highlights
Considerable advances have been made in providing potent antiretroviral therapy to all pregnant and breastfeeding women living with HIV, a substantial gap in available antiretroviral coverage still exists
In resource-constrained settings where fully suppressive antiretroviral therapy may not be available for all pregnant women, the World Health Organization currently recommends intrapartum single-dose nevirapine accompanied by maternal zidovudine and short-course postnatal maternal antiretroviral coverage for women with CD4 cell counts >350 (Option A) [1]
We report on the occurrence of HIV-1 MTCT and the frequency of NVP and nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations among infants born to women in ACTG A5207
Summary
Considerable advances have been made in providing potent antiretroviral therapy to all pregnant and breastfeeding women living with HIV, a substantial gap in available antiretroviral coverage still exists. In resource-constrained settings where fully suppressive antiretroviral therapy may not be available for all pregnant women, the World Health Organization currently recommends intrapartum single-dose nevirapine (sdNVP) accompanied by maternal zidovudine and short-course postnatal maternal antiretroviral coverage for women with CD4 cell counts >350 (Option A) [1]. Prolonged exposure to NVP selects for NVP resistance mutations in exposed mothers and HIV-1- infected infants [3,4], limiting future treatment options for these individuals [5]. Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy
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