Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding

NCT ID: NCT00074412

Last Updated: 2023-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2026 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2011-11-30

Brief Summary

The many benefits of breastfeeding are well documented. However, because of the risk of mother-to-child transmission (MTCT) of HIV from an HIV infected mother to her infant, there is considerable concern over the practice, especially in developing countries. The purpose of this study is to determine the safety and effectiveness of the anti-HIV drug nevirapine (NVP) in preventing MTCT of HIV in breastfeeding infants born to HIV infected women in South Africa, Tanzania, Uganda, and Zimbabwe.

Detailed Description

Breastfeeding provides general health, growth, and development benefits to an infant and significantly decreases the risk of certain acute and chronic diseases. Breastfeeding also decreases financial burden on the mother by decreasing the need for infant formula and health care for the infant. However, clinical evidence has shown that HIV can be readily transmitted through breast milk, although the risk of HIV MTCT over time while breastfeeding has been difficult to determine. Given the many advantages of breastfeeding and the significant obstacles to substituting formula for breast milk in developing countries, there is an urgent need to make breastfeeding by HIV infected women safe. This study will evaluate the safety and efficacy of an extended NVP regimen for prevention of MTCT of HIV through breastfeeding.

This study will last approximately 3.5 years. Mother/infant pairs will be enrolled over a period of 18 to 24 months. During the third trimester of pregnancy, HIV infected participants will receive HIV counseling and the intrapartum/neonatal two-dose NVP prophylaxis regimen to prevent MTCT. Mothers will also be given infant feeding options counseling and information on administering the study drug to the infant. Infants who were randomly assigned to receive a placebo and older than 6 weeks of age as of 08/10/07 OR to receive NVP will continue their treatment assignment. Infants who were randomly assigned to receive a placebo and are 6 weeks of age or less as of 08/10/07 will receive open-label NVP through Day 42 of life. For all other participants, all randomized infants will receive extended NVP through 6 weeks (Day 42) of life. All eligible infants will be randomly assigned to one of two groups at Week 6 following birth. The first group will receive extended NVP treatment; the second group will receive nevirapine placebo. Randomized infants will receive the extended NVP or NVP placebo through the first 6 months of life or until cessation of breastfeeding, whichever occurs earlier. Mothers will be instructed to begin giving their infants their assigned intervention starting at Day 3 to Day 7 postpartum. All mothers and infants outside of the study will be offered the local standard of care antiretroviral (ARV) regimen for the prevention of MTCT, but these ARVs will not be provided by the study.

Follow-up evaluations will be conducted at Weeks 2 and 6 and Months 3, 6, 12, and 18 for mothers, and at Weeks 2, 5, 6, and 8 and Months 3, 4, 5, 6, 9, 12, and 18 for infants. Study visits will include physical examinations, blood tests (including HIV tests), and medical histories. Study participants will be followed for up to 3.5 years.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

2A

For infants: extended treatment with NVP

Group Type: EXPERIMENTAL

Nevirapine

Intervention Type: DRUG

10 mg/ml oral suspension taken once daily up to 6 months of age. Dosage will increase throughout study.

2B

For infants: extended treatment with NVP placebo

Group Type: PLACEBO_COMPARATOR

Nevirapine placebo

Intervention Type: DRUG

Oral suspension taken once daily up to 6 months of age

Interventions

Nevirapine

10 mg/ml oral suspension taken once daily up to 6 months of age. Dosage will increase throughout study.

Intervention Type: DRUG

Nevirapine placebo

Oral suspension taken once daily up to 6 months of age

Intervention Type: DRUG

Other Intervention Names

NVP; NVP placebo

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older
• HIV infected
• In third trimester of pregnancy, or at most 3 days post-delivery
• If baby is not yet born, planning to deliver at a facility where the study is being conducted
• Plan to breastfeed

• Born to an HIV infected mother who is eligible for the study
• Weighed at least 2000 grams (4.4 lbs) at birth
• Blood sample obtained from the infant for HIV-1 DNA PCR, CBC with differential, and ALT
• Infants in a multiple birth are eligible only if both/all infants are eligible for the study and assigned to the same study group
• Able to breastfeed (e.g., mother and infant alive with no condition apparent that would prevent breastfeeding)

Exclusion Criteria

• Complications with this pregnancy
• Serious medical condition that would interfere with the study (e.g., that would prevent breastfeeding or adherence to the follow-up schedule), as judged by the on-site clinician

• HIV DNA PCR positive at birth
• ALT of Grade 2 or higher at birth
• Hemoglobin, absolute neutrophil count, or platelet count of Grade 3 or higher at birth
• Skin rash of Grade 2B (urticaria), Grade 3, or above
• Confirmed or suspected clinical hepatitis
• Serious illness or condition that would interfere with compliance with study procedures

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hoosen M. Coovadia, MD, MBBS

Role: STUDY_CHAIR

Centre for HIV Networking (HIVAN), Nelson Mandela School of Medicine, University of Natal

Laura Guay, MD

Role: STUDY_CHAIR

Johns Hopkins University

Wafaie Fawzi, MD, PhD

Role: STUDY_CHAIR

Department of Nutrition, Harvard School of Public Health

Yvonne Maldonado, MD

Role: STUDY_CHAIR

Stanford University

Daya Moodley, MSc, PhD

Role: STUDY_CHAIR

Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of Natal

Locations

CAPRISA Umlazi CRS

Umlazi, KwaZulu-Natal, South Africa

Muhimbili University of Health and Allied Sciences (MUHAS) CRS

Dar es Salaam, , Tanzania

Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS

Kampala, Mpigi, Uganda

Seke North CRS

Chitungwiza, , Zimbabwe

St Mary's CRS

Chitungwiza, , Zimbabwe

Countries

South Africa; Tanzania; Uganda; Zimbabwe

References

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Other Identifiers

10142

Identifier Type: REGISTRY

Identifier Source: secondary_id

HPTN 046

Identifier Type: -

Identifier Source: org_study_id