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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00074412
Recruitment Status : Completed
First Posted : December 15, 2003
Results First Posted : September 16, 2013
Last Update Posted : September 16, 2013
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Nevirapine Drug: Nevirapine placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2026 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
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
Study Start Date : January 2007
Actual Primary Completion Date : September 2011
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Nevirapine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study [ Time Frame: At Month 6 ]
  2. Frequency and Severity of Adverse Reactions Among Participating Infants [ Time Frame: 6 weeks through 18 months ]
    For those infants who were randomized at 6 weeks and who initiated study drug we looked at the frequency and severity of adverse reactions through 18 months of study. The severity of all AEs was graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. The term severity is described as the intensity grade or level for specific event (i.e. mild, moderate, severe, or life-threatening). Severity is not the same as seriousness.

Secondary Outcome Measures :
  1. Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms [ Time Frame: At Months 6 and 18 ]
  2. Relative Rates of HIV Infection in the Two Arms [ Time Frame: At Month 18 ]
  3. Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms [ Time Frame: At Month 18 ]
  4. Frequency and Duration of Maternal Plasma and Breast Milk NVP-resistant HIV Strains and the Relationship With HIV Transmission [ Time Frame: Throughout study ]
  5. Relationship Between Maternal Plasma and Breast Milk RNA Levels and the Risk of MTCT [ Time Frame: Throughout study ]
  6. Frequency and Duration of NVP-resistant HIV Strains in Plasma of HIV-infected Infants [ Time Frame: Throughout study ]
  7. 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 ]
  8. NVP Concentrations in Infants Determined to be HIV-infected and in a Sample of HIV-uninfected Infants [ Time Frame: Week 8 and Month 3 ]
    Samples for NVP concentration were selected from the Version 3.0 infants who were randomized to NVP at 6 weeks and whose mothers were not on 3 or more antiretrovirals at the time of randomization. All infants HIV-infected by 6 months who met this criteria were selected and matched to HIV-uninfected infants who also met this criteria in a 1:3 ratio. NVP concentrations were measured by high liquid chromatographic/mass spectroscopy from the aforementioned infants plasma samples collected at week 8 and month 3. Median NVP concentrations were compared

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00074412

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South Africa
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
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
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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
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00074412    
Other Study ID Numbers: HPTN 046
10142 ( Registry Identifier: DAIDS ES )
First Posted: December 15, 2003    Key Record Dates
Results First Posted: September 16, 2013
Last Update Posted: September 16, 2013
Last Verified: July 2013
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
Treatment Experienced
Treatment Naive
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers