Clinical trial NCT00074412: Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding
Official title: A Phase III Trial to Determine the Efficacy and Safety of an Extended Regimen of Nevirapine in Infants Born to HIV-Infected Women to Prevent Vertical HIV Transmission During Breastfeeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV Seronegativity
Treatment Experienced
Treatment Naive
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute on Drug Abuse (NIDA)
name: National Institute of Mental Health (NIMH)
First posted: 2003-12-15
Enrollment: 2026
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Note: As of 08/10/07, the arm assignments for current and new participants have changed. Please see the above description for this trial for more information.

Inclusion Criteria for Mothers:

* 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

Exclusion Criteria for Mothers:

* 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

Inclusion Criteria for Infants:

* 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 for Infants:

* 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

Primary outcomes:
measure: HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study
timeFrame: At Month 6
measure: Frequency and Severity of Adverse Reactions Among Participating Infants
timeFrame: 6 weeks through 18 months
Secondary outcomes:
measure: Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms
timeFrame: At Months 6 and 18
measure: Relative Rates of HIV Infection in the Two Arms
timeFrame: At Month 18
measure: Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms
timeFrame: At Month 18
Other outcomes:
Locations:
city: Umlazi
country: South Africa
facility: CAPRISA Umlazi CRS
state: KwaZulu-Natal
city: Dar es Salaam
country: Tanzania
facility: Muhimbili University of Health and Allied Sciences (MUHAS) CRS
city: Kampala
country: Uganda
facility: Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS
state: Mpigi
city: Chitungwiza
country: Zimbabwe
facility: Seke North CRS
city: Chitungwiza
country: Zimbabwe
facility: St Mary's CRS
Study officials:
affiliation: Centre for HIV Networking (HIVAN), Nelson Mandela School of Medicine, University of Natal
name: Hoosen M. Coovadia, MD, MBBS
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Laura Guay, MD
role: STUDY_CHAIR
affiliation: Department of Nutrition, Harvard School of Public Health
name: Wafaie Fawzi, MD, PhD
role: STUDY_CHAIR
affiliation: Stanford University
name: Yvonne Maldonado, MD
role: STUDY_CHAIR
affiliation: Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of Natal
name: Daya Moodley, MSc, PhD
role: STUDY_CHAIR
References:
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