title: Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may decrease resistance after a single dose of nevirapine for perinatal HIV prevention.
abstract: BACKGROUND
  World Health Organization guidelines recommend zidovudine + lamivudine for 7 days from labor onset in HIV-infected women receiving single-dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine concentrations. Although effective, this is complicated and does not eliminate resistance; alternative strategies could add benefit.
  
  
  METHODS
  Antiretroviral-naive HIV-infected pregnant women aged 18-40 years, with CD4 >200 cells per cubic millimeter, able to regularly attend the antenatal clinics in Moshi, Tanzania, were enrolled 1:1 by alternate allocation to receive 200 mg sdNVP alone or in combination with open-label 400-mg single-dose carbamazepine (sdNVP/CBZ) at delivery (ClinicalTrials.gov NCT00294892). The coprimary outcomes were nevirapine plasma concentrations 1 week and nevirapine resistance mutations 6 weeks postpartum. Analyses were based on those still eligible at delivery.
  
  
  RESULTS
  Ninety-seven women were assigned to sdNVP and 95 to sdNVP/CBZ during pregnancy, of whom 75 sdNVP and 83 sdNVP/CBZ were still eligible at delivery at study sites. The median (interquartile range) nevirapine plasma concentration was 1.55 (0.88-1.84) mg/L in sdNVP (n = 61) and 1.40 (0.93-1.97) mg/L in sdNVP/CBZ (n = 72) at delivery (P = 0.91), but 1 week later was significantly lower in sdNVP/CBZ [n = 63; 0.09 (0.05-0.20) mg/L] than in sdNVP [n = 52; 0.20 (0.09-0.31) mg/L; rank-sum: P = 0.004] (geometric mean ratio: 0.64, 95% confidence interval: 0.43 to 0.96; P = 0.03). Six weeks postpartum, nevirapine mutations were observed in 11 of 52 (21%) in sdNVP and 6 of 55 (11%) in sdNVP/CBZ (odds ratio = 0.46, 95% confidence interval: 0.16 to 1.34; P = 0.15).
  
  
  CONCLUSIONS
  Addition of single-dose carbamazepine to sdNVP at labor onset in HIV-infected, pregnant women did not affect nevirapine plasma concentration at delivery, but significantly reduced it 1 week postpartum, with a trend toward fewer nevirapine resistance mutations.
authors: Department of Pharmacology, Kilimanjaro Christian Medical College, Moshi, Tanzania.
authors: Eva P
authors: EP
authors: Muro
authors: Quirine
authors: Q
authors: Fillekes
authors: Elton R
authors: ER
authors: Kisanga
authors: Rafaëlla
authors: R
authors: L'homme
authors: Susan C
authors: SC
authors: Aitken
authors: Godfrey
authors: G
authors: Mariki
authors: Andre J A M
authors: AJ
authors: Van der Ven
authors: Wil
authors: W
authors: Dolmans
authors: Rob
authors: R
authors: Schuurman
authors: A Sarah
authors: AS
authors: Walker
authors: Diana M
authors: DM
authors: Gibb
authors: David M
authors: DM
authors: Burger
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002220:Carbamazepine / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009154:Mutation; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D002220:Carbamazepine; D019829:Nevirapine