title: Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand.
abstract: OBJECTIVE
  Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis.
  
  
  METHODS
  PHPT-5 was a randomized, partially double-blind placebo-controlled, noninferiority trial in Thailand (NCT00409591). Study participants were women with CD4 of at least 250 cells/μl and their infants.
  
  
  METHODS
  All women received ZDV from 28 weeks' gestation and their newborn infants for one week. Women were also randomized to receive NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day 'tail' of ZDV along with lamivudine, and infant NVP (one dose immediately, another 48 h later); infant-only NVP: maternal placebos for sdNVP and the 'tail', with infant NVP; LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV-diagnosis was determined by DNA-PCR.
  
  
  RESULTS
  Four-hundred and thirty-five women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% confidence interval: 1.2-8.6) in NVP-NVP, 1.6% (0.2-5.6) in infant-only NVP, and 1.4% (0.4-5.1) in LPV/r arms. As-treated rates were 2.2% (0.5-6.4), 3.2% (0.9-7.9), and 1.5% (0.2-5.2), respectively. Factors independently associated with transmission were prophylaxis duration less than 8 weeks (adjusted odds ratio 15.5; 3.6-66.1) and viral load at baseline at least 4 log10copies/ml (adjusted odds ratio 10.9; 1.3-91.5). Regimens appeared well tolerated.
  
  
  CONCLUSIONS
  Transmission rates in all arms were low but noninferiority was not proven. Antiretroviral prophylaxis for at least 8 weeks before delivery is necessary to minimize transmission risk.
authors.affiliation: aUnité Mixte Internationale 174, Institut de Recherche pour le Développement (IRD)-PHPT, Chiang Mai, Thailand bDepartment of Immunology and Infectious, Diseases, Harvard School of Public Health, Boston, Massachusetts, USA cDepartment of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand dUnité Mixte de Recherche 196, Centre Français de la Population et du Développement, (INED-IRD-Paris V University), Paris, France eDepartment of Statistics, Faculty of Science, Chiang Mai University, Chiang Mai fSanpatong Hospital, Ministry of Public Health, Sanpatong gSamutprakarn Hospital, Ministry of Public Health, Samutprakarn hBanglamung Hospital, Ministry of Public Health, Chonburi, Thailand iChildren's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA jFamily Health Research Center, Mahidol University, Bangkok, Thailand.
authors.forename: Marc
authors.initials: M
authors.lastname: Lallemant
authors.forename: Sophie
authors.initials: S
authors.lastname: Le Coeur
authors.forename: Wasna
authors.initials: W
authors.lastname: Sirirungsi
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Nicole
authors.initials: N
authors.lastname: Ngo-Giang-Huong
authors.forename: Patrinee
authors.initials: P
authors.lastname: Traisathit
authors.forename: Virat
authors.initials: V
authors.lastname: Klinbuayaem
authors.forename: Prapan
authors.initials: P
authors.lastname: Sabsanong
authors.forename: Prateep
authors.initials: P
authors.lastname: Kanjanavikai
authors.forename: Gonzague
authors.initials: G
authors.lastname: Jourdain
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mcintosh
authors.forename: Suporn
authors.initials: S
authors.lastname: Koetsawang
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000008:administration & dosage*; D010919:Placebos / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D013785:Thailand; D016896:Treatment Outcome; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D010919:Placebos; D015215:Zidovudine; D019829:Nevirapine