Two-Dose Intrapartum/Newborn Nevirapine and Standard Antiretroviral Therapy to Reduce Perinatal HIV Transmission
A Randomized Trial
- Alejandro Dorenbaum, MD;
- Coleen K. Cunningham, MD;
- Richard D. Gelber, PhD;
- Mary Culnane, MS, CRNP;
- Lynne Mofenson, MD;
- Paula Britto, MS;
- Claire Rekacewicz, MD;
- Marie-Louise Newell, PhD;
- Jean Francois Delfraissy, MD;
- Bethann Cunningham-Schrader, MS;
- Mark Mirochnick, MD;
- John L. Sullivan, MD;
- for the International PACTG 316 Team
- Author Affiliations: Department of Pediatrics, University of California, San Francisco (Dr Dorenbaum); Department of Pediatrics, State University
of New York Upstate Medical University, Syracuse (Dr Cunningham); Statistical and Data Analysis Center, Harvard School of
Public Health, Boston, Mass (Dr Gelber and Ms Britto); National Institute of Allergy and Infectious Diseases, Rockville, Md
(Ms Culnane); National Institute of Child Health and Human Development, Bethesda, Md (Dr Mofenson); Agence Nationale de Recherches
sur le SIDA, Villejuif, France (Drs Rekacewicz and Delfraissy); INSERM SC10, Villejuif, France (Dr Rekacewicz); Centre for
Paediatric Epidemiology and Biostatistics, Institute of Child Health, London, England (Dr Newell); Enquete Perinatale Francaise,
CHU BICETRE, Paris, France (Dr Delfraissy); Frontier Science, Buffalo, NY (Ms Cunningham-Schrader); Department of Pediatrics,
Boston University School of Medicine, Boston, Mass (Dr Mirochnick); and Department of Pediatrics and Molecular Medicine, University
of Massachusetts Medical School, Worcester (Dr Sullivan). Dr Dorenbaum is now at Chiron Corp, Emeryville, Calif.
Dr Newell represents the European Collaborative Study.
Abstract
Context A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatal antiretroviral therapy (ART). However, it is unknown whether the addition of the 2-dose nevirapine regimen to standard ART would further reduce perinatal HIV transmission.
Objective To determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving standard ART.
Design and Setting International, blinded, placebo-controlled, phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States, Europe, Brazil, and the Bahamas.
Participants A total of 1270 women received nevirapine (n = 642) or placebo (n = 628). Infants were followed up for 6 months to determine HIV-infection status, which was available for 1248 deliveries.
Intervention A 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth.
Main Outcome Measures Detection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns.
Results After review by the data and safety monitoring board, the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design. Antenatal ART included zidovudine alone in 23%; combinations without protease inhibitors in 36%; and combinations with protease inhibitors in 41%. Thirty-four percent of women had elective cesarean delivery. No significant safety concerns were identified for women or infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidence interval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%; 95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the difference in transmission rate (−0.2) between the 2 study arms ranged from −1.5% in favor of nevirapine to 1.2% in favor of placebo (P = .82, Fisher exact test). The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels, but there was no significant difference between treatment arms in any subgroup.
Conclusion Risk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART, and elective cesarean section was made available.
