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

A Phase III Placebo-Controlled Trial to Determine the Efficacy of Oral AZT and the Efficacy of Oral Nevirapine for the Prevention of Vertical Transmission of HIV-1 Infection in Pregnant Ugandan Women and Their Neonates

The purpose of this study is to see if nevirapine (NVP) or zidovudine (AZT), given to mothers during labor and delivery and to their babies during the first week of life, can reduce the rate of mothers passing HIV to their babies.

About 25 percent of HIV-infected mothers pass HIV infection to their babies during labor and delivery. There is an urgent need to find a simpler way to prevent mother-to-infant transmission during labor and delivery. The proposed NVP schedule is simpler and possibly could be used in Uganda.

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.