title: A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.
abstract: BACKGROUND
  Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal transmission of human immunodeficiency virus (HIV) infection but selects for NVP-resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail" of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We hypothesized that increasing the duration or potency of the tail would further reduce this risk to <10%, using a sensitive assay to measure resistance.
  
  
  METHODS
  HIV-infected pregnant Thai women with a CD4 cell count >250 cells/μL, most receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3 intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric-coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP resistance mutations at day 10 or week 6 post partum in each arm was compared with that of a historical comparison group who received prenatal zidovudine and SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive oligonucleotide ligation assay (OLA).
  
  
  RESULTS
  At entry, the 169 participants had a median CD4 cell count of 456 cells/μL and an HIV load of 3.49 log(10) copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively, compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P < .001 for each study arm vs comparison group). Grade 4 anemia developed in 1 woman.
  
  
  CONCLUSIONS
  A 7-day tail of highly active combination therapy or 1 month of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity.
  
  
  BACKGROUND
  The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684.
authors.affiliation: Department of Pediatrics, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. vandyke@tulane.edu
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: Nicole
authors.initials: N
authors.lastname: Ngo-Giang-Huong
authors.forename: David E
authors.initials: DE
authors.lastname: Shapiro
authors.forename: Lisa
authors.initials: L
authors.lastname: Frenkel
authors.forename: Paula
authors.initials: P
authors.lastname: Britto
authors.forename: Anuvat
authors.initials: A
authors.lastname: Roongpisuthipong
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Beck
authors.forename: Praparb
authors.initials: P
authors.lastname: Yuthavisuthi
authors.forename: Sinart
authors.initials: S
authors.lastname: Prommas
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.forename: Jullapong
authors.initials: J
authors.lastname: Achalapong
authors.forename: Nantasak
authors.initials: N
authors.lastname: Chotivanich
authors.forename: Wirawan
authors.initials: W
authors.lastname: Rasri
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Robert
authors.initials: R
authors.lastname: Maupin
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
authors.forename: Gonzague
authors.initials: G
authors.lastname: Jourdain
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine; D019829:Nevirapine