title: Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Perinatal 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.
  
  
  CONCLUSIONS
  Infants 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.
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Hitti
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Elias K
authors.initials: EK
authors.lastname: Halvas
authors.affiliation: Harvard School of Public Health, Boston, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Panousis
authors.affiliation: Joint Clinical Res Center, Kampala, Uganda.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kabanda
authors.affiliation: Queen Elizabeth Ctrl Hospital, Blantyre, Malawi.
authors.forename: Frank
authors.initials: F
authors.lastname: Taulo
authors.affiliation: YRGCARE Medical Centre, Chennai, India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: Weill Cornell Medical College, New York, NY and Les Centres GHESKIO, Port-au-Prince, Haiti, Newyork, USA.
authors.forename: Jean William
authors.initials: JW
authors.lastname: Pape
authors.affiliation: Durban Adult HIV CRS, Durban, South Africa.
authors.forename: Umesh
authors.initials: U
authors.lastname: Lalloo
authors.affiliation: Frontier Sci Tech and Research Foundation, Amherst, NY, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Sprenger
authors.affiliation: TRP, DAIDS, NIH, Bethesda, MD, USA.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.affiliation: Harvard School of Public Health, Boston, MA, USA.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Chan
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: McMahon
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
keywords: Antiretroviral resistance; Clinical trials registration: clinicaltrials.gov (NCT00099632); HIV-1 Perinatal transmission; Infant; Inhibitors; Nevirapine; Nucleoside reverse transcriptase