Effectiveness of AZT and Nevirapine in Preventing HIV Transmission From Ugandan Mothers to Their Newborns

There is an urgent need to find a safe, effective means of preventing mother-to-infant HIV transmission that would also be applicable and affordable in developing-country settings. The frequency of vertical HIV-1 transmission is estimated to be 25 percent. The proposed trial specifically will test the hypothesis that chemoprophylaxis of the fetus/neonate during labor and delivery and the first week of life may significantly reduce the risk of perinatal HIV-1 transmission.

Pregnant women infected with HIV-1 are randomized to 1 of 4 study arms and receive either NVP or its placebo, or AZT or its placebo. Mothers in the NVP group receive a single dose of NVP or placebo at the onset of labor and are followed to 6 to 8 weeks after delivery. Infants born to these mothers receive at 48 to 72 hours post-delivery or discharge, whichever comes first, a regimen of the same treatment (NVP or placebo) given to the mother. Infants are followed for 18 months post-delivery by clinical and laboratory evaluation to determine toxicity, evidence of HIV-1 infection, and clinical disease progression.

Mothers in the AZT group receive either a bolus of AZT or its placebo at onset of labor, then doses every 3 hours until delivery, with follow-up to 6 to 8 weeks. Infants begin receiving either a lower dose of AZT or placebo as soon as they can tolerate liquids by mouth, twice daily for 7 days, and are followed for 18 months as in the NVP group.

Inclusion criteria

Mothers may be eligible for this study if they:

• Have been pregnant for more than 32 weeks and are at least 18 years of age.
• Are HIV-positive.
• Reside within 15 km of Mulago Hospital, the study site.
• Infants may be eligible for this study if they:
• Are born to mothers enrolled in the study.
• Have consent of the mother/guardian and, if available, the father.

Exclusion criteria

Mothers will not be eligible for this study if they:

• Have a serious infection or illness other than HIV.
• Currently take any anti-HIV drugs.
• Participate during this pregnancy in another treatment vaccine perinatal trial.
• Received NVP or AZT within the last 6 months.
• Are allergic to any benzodiazepine.
• Abuse alcohol or other drugs.
• Have high blood pressure that is not controlled.
• Have received any anticoagulants, benzodiazepines other than the study drug, or magnesium sulfate within 2 weeks before being assigned to a study group or delivery.
• Infants will not be eligible for this study if:
• Their mother is excluded prior to being assigned to a study group.