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 receivednevirapine (n = 642) orplacebo (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.
RCT Entities:
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.
Authors: Susan B Brogly; Mark J Abzug; D Heather Watts; Coleen K Cunningham; Paige L Williams; James Oleske; Daniel Conway; Rhoda S Sperling; Hans Spiegel; Russell B Van Dyke Journal: Pediatr Infect Dis J Date: 2010-08 Impact factor: 2.129
Authors: Cristina M Marazzi; Paola Germano; Giuseppe Liotta; Giovanni Guidotti; Sandra Loureiro; Aurelio da Cruz Gomes; Maria C Valls Blazquez; Pasquale Narciso; Carlo F Perno; Sandro Mancinelli; Annamaria Doro Altan; Karin Nielsen-Saines; Leonardo Palombi Journal: Eur J Pediatr Date: 2007-01-18 Impact factor: 3.183
Authors: June M McKoy; Charles L Bennett; Marc H Scheetz; Virginia Differding; Kevin L Chandler; Kimberly K Scarsi; Paul R Yarnold; Sarah Sutton; Frank Palella; Stuart Johnson; Eniola Obadina; Dennis W Raisch; Jorge P Parada Journal: Drug Saf Date: 2009 Impact factor: 5.606
Authors: Andrea L Ciaranello; George R Seage; Kenneth A Freedberg; Milton C Weinstein; Shahin Lockman; Rochelle P Walensky Journal: AIDS Date: 2008-11-12 Impact factor: 4.177