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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
JAMA. 2002;288:189-198.
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.
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.
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