title: Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants.
abstract: BACKGROUND
  The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis.
  
  
  METHODS
  HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables.
  
  
  RESULTS
  NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003).
  
  
  CONCLUSIONS
  Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Fogel
authors.forename: Anthony
authors.initials: A
authors.lastname: Mwatha
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Brown
authors.forename: Tsungai
authors.initials: T
authors.lastname: Chipato
authors.forename: Michel
authors.initials: M
authors.lastname: Alexandre
authors.forename: Dhayendre
authors.initials: D
authors.lastname: Moodley
authors.forename: Ali
authors.initials: A
authors.lastname: Elbireer
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
authors.forename: Kathleen
authors.initials: K
authors.lastname: George
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Sheryl
authors.initials: S
authors.lastname: Zwerski
authors.forename: Hoosen M
authors.initials: HM
authors.lastname: Coovadia
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001942:Breast Feeding; D018890:Chemoprevention / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage* / Q000494:pharmacology; D010919:Placebos; D012367:RNA, Viral / Q000235:genetics; D013636:Tanzania; D016896:Treatment Outcome; D014454:Uganda; D015030:Zimbabwe
chemical_list: D044966:Anti-Retroviral Agents; D010919:Placebos; D012367:RNA, Viral; D019829:Nevirapine