Daily Nevirapine to Prevent Mother to Infant Transmission of HIV

Study Overview
=================
Brief Summary
-----------------
Infants who are breast-fed by HIV infected mothers have an increased risk of becoming infected with HIV. Standard therapy for the prevention of HIV infections in infants included zidovudine (ZDV) prior to the onset of labor, a single dose of nevirapine (NVP) for women during labor, and a single dose of NVP for newborns given 72 hours after birth. This study will determine if giving low dose daily NVP to breastfed infants of HIV infected mothers, in addition to standard therapy, will be more effective than standard therapy alone at preventing HIV infections in these infants.

Detailed Description
-----------------
This study will evaluate the safety and effectiveness of adding daily infant NVP to standard prevention measures to decrease vertical transmission of HIV. According to current statistics from the study site, approximately 70% of the pregnant HIV infected women in this study will have begun antenatal ZDV prior to the initiation of NVP at labor. The remaining 30% of the HIV infected women enrolled in this trial will have been previously undiagnosed. These women will be diagnosed with HIV infection either at the time they present to the delivery room in stage 1 of labor or immediately postpartum if they present for delivery late in labor and cannot provide informed consent for HIV screening prior to delivery. All infants will receive the standard does of NVP at 72 hours postpartum. Infants will then be randomized to receive either daily NVP and a daily multivitamin (MVI) or a daily MVI alone. Infants will take NVP/MVI or MVI alone during Weeks 2 to 6 postpartum. The primary outcome measure is infant HIV infection rates at 6 months. Two additional related cohorts of women will be followed for comparison: 1) an equal number of HIV uninfected women and their children will be enrolled for comparison of postpartum morbidity and mortality; and 2) consenting HIV infected women and their children who choose not to enroll in the clinical trial or are ineligible because they are not breastfeeding will be enrolled in an ancillary cohort.

Official Title
-----------------
Prevention of Maternal to Infant HIV Transmission in India

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Nevirapine and mulitvitamins


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for Pregnant or Postpartum Mothers HIV infected Planning to breastfeed Able to tolerate oral drugs and available for 12 months of postpartum follow-up Exclusion Criteria Significant physical or emotional distress Infant with serious or life threatening disease or severe fetal abnormality Obstetrical complications affecting maternal health Prior antiretroviral drugs (except antenatal ZDV or intrapartum (NVP)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day) week 1 through week 6 post-partum | Drug: Nevirapine and mulitvitamins<br>* Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day) week 1 through week 6 post-partum Infants (Arm 2 Only): Liquid nevirapine (5 mg/day) by mouth, from week 1 through week 6 post-partum<br>* Other names: Viramune® (Boehringer Ingelheim);|
| Experimental: 2<br>Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day)by mouth, from week 1 through week 6 post-partum Infants: Liquid nevirapine (5 mg/day) by mouth, from week 1 through week 6 post-partum | Drug: Nevirapine and mulitvitamins<br>* Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day) week 1 through week 6 post-partum Infants (Arm 2 Only): Liquid nevirapine (5 mg/day) by mouth, from week 1 through week 6 post-partum<br>* Other names: Viramune® (Boehringer Ingelheim);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV infection rate of infants |  | 6 months of age | 
| Safety of the regimens for HIV-infected mothers and their breast-fed infants |  | Through 12 months post-partum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability and compliance of intervention regimens |  | Until 6 weeks of age | 
| Time to HIV infection by treatment regimen |  | over 12 months of age | 
| Time to infection by infant feeding practice and time to weaning |  | Until 12 months post-partum | 
| Maternal ZDV and NVP resistance |  | Baseline and post-partum | 
| Infant morbidity and mortality by treatment arm |  | Until 12 months post partum | 
| Infant NVP resistance by treatment arm |  | Up to 12 months post partum | 
| Maternal NVP pharmacokinetics |  | Up to 12 months post-partum | 
| Infant NVP pharmacokinetics |  | Up to 12 months post-partum | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nevirapine, Pregnancy, Maternal to Infant transmission, Infant, Breastfeeding, HIV Seronegativity