A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine

Clin Infect Dis. 2012 Jan 15;54(2):285-93. doi: 10.1093/cid/cir798. Epub 2011 Dec 5.

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.

Clinical trials registration: The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Drug Administration Schedule
  • Drug Resistance, Viral / genetics
  • Female
  • HIV / drug effects
  • HIV / genetics*
  • HIV Infections / drug therapy*
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • Humans
  • Infectious Disease Transmission, Vertical / prevention & control
  • Middle Aged
  • Mutation*
  • Nevirapine / administration & dosage*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy Complications, Infectious / virology
  • Treatment Outcome
  • Viral Load
  • Zidovudine / administration & dosage

Substances

  • Anti-HIV Agents
  • Zidovudine
  • Nevirapine

Associated data

  • ClinicalTrials.gov/NCT00109590
  • ClinicalTrials.gov/NCT00398684