Nevirapine Study for the Prevention of Maternal-Infant HIV Transmission in Uganda

Condition(s) targeted: HIV Infections

Intervention: Nevirapine (Drug); HIV immune globulin solution (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Brooks Jackson, MD, Principal Investigator, Affiliation: Johns Hopkins School of Medicine

The increase in pediatric HIV infection has a substantial impact on childhood mortality in the developing world. A number of recent studies suggest that as many as half or more of mother-to-child HIV transmissions in developing countries occur in late pregnancy or during labor and delivery. Interventions targeted during the perinatal period have shown to be effective and to have a significant impact in reducing transmission. The purpose of this study is to investigate the effectiveness of nevirapine (NVP) plus immunoprophylaxis or extended NVP dosing regimens in HIV-infected pregnant women and their infants during the perinatal period.

Official title: A Phase III Randomized Clinical Trial of the Standard Two Dose Nevirapine (NVP) Regimen With the Addition of HIV Immune Globulin(HIVIGLOB) or Extended Infant NVP Dosing Compared With the Standard NVP Regimen Alone for the Prevention of Maternal-Infant HIV Transmission in Uganda

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver), Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Rate of HIV infection in infants born to study participants in each arm of the study

Safety and tolerance of HIVIGLOB given to pregnant women at 36-37 weeks gestation and neonates at birth in combination with NVP and of NVP alone

Secondary outcome:

Rate of immunologic progression in HIV-infected infants in each arm

Infant mortality

Maternal plasma HIV RNA levels at delivery

Immunologic, virologic, and pharmacologic factors

Detailed description: There is an urgent need to find safe, effective means of preventing mother-to-child-transmission (MTCT) of HIV that can be used in developing countries. One of the greatest obstacles to prevention in these areas remains HIV transmission through breast milk. The primary purpose of this trial is to determine if nevirapine (NVP) plus immunoprophylaxis (by intravenous HIV immune globulin [HIVIGLOB]) or extended NVP dosing of the neonate during the perinatal period can safely and effectively reduce the risk of peripartum or early breastfeeding-related HIV MTCT.

This study will last 11-18 weeks for each mother and 18 months for each infant. HIV-infected pregnant women will be randomly assigned to one of three arms. Participants in Arm 1 will receive a single dose of 200 mg NVP orally at the onset of labor. Infants in Arm 1 will receive a single dose of 2 mg/kg NVP orally within the first week after delivery. Arm 2 participants will receive a single dose of 200 mg NVP orally at the onset of labor. Infants in Arm 2 will receive 2 mg/kg NVP orally within the first week after delivery and 5 mg NVP taken orally daily from Day 8 through Week 6. Arm 3 participants will receive a 12 gm intravenous dose of HIVIGLOB at 36-37 weeks gestation and 200 mg NVP orally at the onset of labor. Infants in Arm 3 will receive a single 1. 2 gm intravenous dose HIVIGLOB within 18 hours of birth and 2 mg/kg NVP orally within the first week after delivery.

There will be five or six study visits for pregnant participants. A targeted medical history, physical examination, and blood collection will occur at all visits. After birth, there will be 11 study visits for infants in Arms 1 and 2 and 12 study visits for infants in Arm 3. Medical history and a targeted physical exam will occur at all visits. Blood collection will occur at some visits.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Pregnant between 32-36 weeks estimated gestation

- HIV Infected

- Intent to breastfeed infant

- Certain laboratory criteria. More information on this criterion can be found in the

protocol.

Exclusion Criteria:

- Sensitivity to immune globulin preparations or any benzodiazepine

- Clinically significant disease, as determined by the investigator, that would

compromise the ability of the participant to complete the study requirements

- Currently receiving antiretroviral therapy (other than the intrapartum NVP or other

peripartum regimens)

- Participation in any HIV vaccine trials

- History of cytotoxic chemotherapy within one month of study entry

- Uncontrolled hypertension

- Chronic alcohol or illicit drug use

- History of non-compliance with visits or medication

- Women who become pregnant again during study follow-up will not be eligible for

re-enrollment in the trial

Related publications:

Colvin M, Chopra M, Doherty T, Jackson D, Levin J, Willumsen J, Goga A, Moodley P; Good Start Study Group. Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV. Bull World Health Organ. 2007 Jun;85(6):466-73.

Flys TS, Mwatha A, Guay LA, Nakabiito C, Donnell D, Musoke P, Mmiro F, Jackson JB, Eshleman SH. Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. AIDS. 2007 Oct 1;21(15):2077-82.

Jackson JB, Musoke P, Fleming T, Guay LA, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Owor M, Ducar C, Deseyve M, Mwatha A, Emel L, Duefield C, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Gigliotti M, Bray D, Mmiro F. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-68.

Starting date: July 2004
Ending date: July 2007
Last updated: April 1, 2008