Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

Study Overview
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Brief Summary
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The purpose of this study was to assess the efficacy of a single dose of the drug nevirapine (NVP) given to pregnant women at onset of labor and to their infant 48-72 hours after birth in addition to standard oral zidovudine (ZDV or AZT) prophylaxis for the prevention of mother-to-child transmission of HIV-1.

Detailed Description
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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%.

Conditions
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HIV Infections, Pregnancy

Intervention / Treatment
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* Drug: Single dose nevirapine to the mother and to the child
* Drug: Single dose nevirapine to the mother and placebo to the child
* Drug: Single dose placebo to the mother and to the child


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth (NVP-NVP) | Drug: Single dose nevirapine to the mother and to the child<br>* One maternal 200 mg NVP dose at the onset of labor, and one dose of infant NVP (0.6 ml/6mg) between 48-72 hours after birth. [Infants less than 2,500g received only 0.2mL/kg]<br>|
| Experimental: 2<br>One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth. (NVP-Placebo) | Drug: Single dose nevirapine to the mother and placebo to the child<br>* One maternal 200 mg NVP dose at the onset of labor, and one dose of infant placebo (0.6 ml) between 48-72 hours after birth. [Infants less than 2,500g received only 0.2mL/kg]<br>|
| Placebo Comparator: 3<br>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. (Placebo-Placebo) | Drug: Single dose placebo to the mother and to the child<br>* One maternal placebo dose at the onset of labor, and one dose of infant placebo (0.6 ml) between 48-72 hours after birth. [Infants less than 2,500g received only 0.2mL/kg]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of nevirapine, in particular rashes. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thailand, Developing countries, prophylaxis, mother to child transmission, HIV-1, HIV-1 infection, HIV Seronegativity