Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

Multicenter, randomized, three arms, double-blind, controlled study. Study population was HIV-infected pregnant women who were on ZDV prophylaxis for more than two weeks and gave informed consent. If eligible, women completed a baseline check-up. Women meeting selection criteria were randomly assigned to receive one of three study regimens, in addition to ZDV prophylaxis:

• One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth
• One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth
• One dose maternal placebo at onset of labor, and one dose of infant placebo 48-72 hours after birth. This was the reference study arm.

Follow-up of women and infants was carried out on an outpatient basis except for delivery and the first three days after delivery.

AMENDMENT

After the first interim analysis, enrollment in Placebo-Placebo arm was terminated on May 2, 2002, according to the recommendation of the Data and Safety Monitoring Board. The target sample size was increased to 660, instead of 510, in each of the two remaining arms (N-N and N-P) to ensure enough power to test for non-inferiority between these arms with a limit of 2.5%.

Pre-Entry Criteria

Women were eligible for the study if they:

• have evidence of HIV infection (documented by two HIV antibody tests on two different dates);
• were to be provided ZDV Prophylaxis (starting at 28 weeks or as soon as possible thereafter);
• intended to carry the pregnancy to term;
• intended to deliver at and bring their infant to a study site for at least 12 months after delivery; and
• could provide informed consent.

Inclusion criteria

Women are eligible for the study if they:

• met all pre-entry criteria;
• agreed not to breastfeed;
• consented to participate and to be followed for the duration of the study;
• presented the following laboratory values within 14 days prior to randomization:
• hemoglobin > 8.0 mg/dl
• absolute neutrophil count > 1000 cells/mm3
• platelets > 100,000 cells/mm3
• serum creatinine < 1.5 mg/dl (women with a serum creatinine > 1.5 mg/dl must have a measured eight-hour urine creatinine clearance > 70 ml/min)
• SGPT less than 10 times the upper limit of normal NOTE: Women with a Grade 2 or Grade 3 SGPT value (between 2.6 and 10 times the upper limit of normal) were allowed on study; they were monitored monthly until delivery. If at any point their SGPT value rose to a Grade 4 (more than 10 times the upper limit of normal), they should not be dosed with the Study Drug.

Exclusion criteria

• evidence of pre-existing fetal anomalies incompatible with life;
• known hypersensitivity to any benzodiazepine or to NVP;
• receipt of antiretroviral agent other than ZDV;
• receipt of non-allowed concomitant treatment;
• uncontrolled hypertension;
• concurrent participation in another clinical trial;
• women with a CD4 count <200/µL or history of oral candidiasis if they were not receiving PCP prophylaxis.