Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: Nevirapine Drug: Nevirapine placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver) Primary Purpose: Prevention |
| 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 |
- HIV infection in infants determined to be HIV uninfected at 6 weeks enrolled in each arm of the study [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
- Frequency and severity of adverse reactions among participating infants [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Proportion of infants who are alive and HIV-uninfected in the two arms [ Time Frame: At Months 6 and 18 ] [ Designated as safety issue: No ]
- Relative rates of HIV infection in the two arms [ Time Frame: At Month 18 ] [ Designated as safety issue: No ]
- Infant survival rates (mortality regardless of HIV infection) in the two arms [ Time Frame: At Month 18 ] [ Designated as safety issue: Yes ]
- Frequency and duration of maternal plasma and breast milk NVP-resistant HIV strains and the relationship with HIV transmission [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Relationship between maternal plasma and breast milk RNA levels and the risk of MTCT [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Frequency and duration of NVP-resistant HIV strains in plasma of HIV-infected infants [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Rates of disease progression as defined by CD4 counts, HIV-1 RNA PCR, and mortality in infected infants in the two arms [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- NVP concentrations in infants determined to be HIV-infected and in a sample of HIV-uninfected infants [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 1670 |
| Study Start Date: | January 2007 |
| Study Completion Date: | February 2011 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 2A
For infants: extended treatment with NVP
|
Drug: Nevirapine
10 mg/ml oral suspension taken once daily up to 6 months of age. Dosage will increase throughout study.
Other Name: NVP
|
|
Placebo Comparator: 2B
For infants: extended treatment with NVP placebo
|
Drug: Nevirapine placebo
Oral suspension taken once daily up to 6 months of age
Other Name: NVP placebo
|
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| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| South Africa | |
| Prince Mshiyeni Hospital | |
| Durban, South Africa | |
| CAPRISA Umlazi CRS | |
| Durban, South Africa | |
| Tanzania | |
| Muhimbili Hospital | |
| Dar es Salaam, Tanzania | |
| Uganda | |
| Mulago Hospital | |
| Kampala, Uganda | |
| Zimbabwe | |
| Chitungwiza Clinics | |
| Harare, Zimbabwe | |
| Seke North | |
| Harare, Zimbabwe | |
| Study Chair: | Hoosen M. Coovadia, MD, MBBS | Centre for HIV Networking (HIVAN), Nelson Mandela School of Medicine, University of Natal |
| Study Chair: | Laura Guay, MD | Johns Hopkins University |
| Study Chair: | Wafaie Fawzi, MD, PhD | Department of Nutrition, Harvard School of Public Health |
| Study Chair: | Yvonne Maldonado, MD | Stanford University |
| Study Chair: | Daya Moodley, MSc, PhD | Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of Natal |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00074412 History of Changes |
| Other Study ID Numbers: | HPTN 046, 10142 |
| Study First Received: | December 11, 2003 |
| Last Updated: | October 4, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
HIV Seronegativity Treatment Experienced Treatment Naive |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases |
Nevirapine Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on March 14, 2013
