1. Among pregnant women with HIV, antepartum, intrapartum and neonatal zidovudine therapy reduced maternal-fetal transmission of HIV by two-thirds.
Original Date of Publication: November 1994
Study Rundown: The primary means of human immunodeficiency virus (HIV) infection in young children is maternal-infant transmission. In the 1990s, a staggering 15-45% of infants delivered to women with HIV were expected to be infected, mostly during the process of labor and delivery. Despite medicine’s best treatments, pediatric HIV infection remained a fatal disease, underscoring the importance of preventing transmission. Prior research demonstrated that zidovudine (AZT) reduced maternal transmission of HIV in animal models and promising Phase I studies in pregnant women suggested that zidovudine was safe for use. In the present work, researchers hypothesized that zidovudine administered in the antepartum, intrapartum and neonatal periods would reduce maternal-infant transmission of HIV. After the first interim analysis demonstrated clear benefit to zidovudine therapy for reduction of maternal-infant HIV transmission, the Data Safety Monitoring Board altered study protocol to offer zidovudine to all women. Findings of the present work summarize results of the trial through this first interim analysis.
This landmark study demonstrated that treatment of HIV-positive pregnant women with mild disease (CD4 counts >200) with zidovudine (AZT) achieved a two-thirds reduction in the maternal-fetal transmission of HIV. Findings from the landmark, AIDS Clinical Trials Group 076 (ACTG 076) trial affected a meaningful risk reduction in maternal-infant HIV transmission. Subsequently, in resource-rich settings, the risk of maternal-infant HIV transmission dropped from 20-45% (no treatment) to <1% (antepartum, intrapartum and neonatal antiretroviral therapy and abstinence from breastfeeding and cesarean delivery at 37 weeks for maternal HIV viral load >1000). Strengths included multicenter, international trial with parsimonious randomized, controlled and double-blinded design and outcome ascertainment at multiple times. Limitations include lack of confirmation of HIV diagnosis with polymerase chain reaction and enrollment of women only after the first trimester of pregnancy due to teratogenicity concerns. Further, results do not apply to women with advanced or drug-resistant disease.
Dr. Alan Peaceman, MD, talks to 2 Minute Medicine: Northwestern University School of Medicine; Chief, Division of Obstetrics and Gynecology-Maternal Fetal Medicine.
“This study demonstrated that a regimen of zidovudine incorporating antepartum, intrapartum and neonatal administration reduces rates of maternal-fetal HIV transmission by more than two-thirds. Findings support the universal administration of antiretroviral therapy in the antepartum period, zidovudine intravenously in labor and zidovudine syrup for neonates of pregnant women with HIV.”
In-Depth [randomized controlled trial]: A total of 363 HIV-positive pregnant women with CD4 counts >200 not previously on antiretroviral therapy were randomized to receive zidovudine (n=180) or placebo (n=183) in this multicenter, international (U.S. and France) clinical trial by the AIDS Clinical Trials Group (ACTG 076). Women randomized to zidovudine received antepartum zidovudine orally 5 times daily, intrapartum intravenous zidovudine and zidovudine for the newborn for the first 6 weeks of life. Primary outcome was the incidence of HIV infection among newborns at 18 months of age as detected by enzyme immunoassay, Western blot and serial HIV cultures.
Pregnant, HIV-positive women randomized to receive zidovudine in the antepartum, intrapartum and neonatal periods experienced a 67.5% risk reduction in maternal-fetal HIV transmission (95% CI: 0.41-0.82, P=0.00006). The proportion of HIV-infected infants among women in the ziodovudine treatment group was 8% compared to 26% among women in the placebo group.
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