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

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00074412
First received: December 11, 2003
Last updated: July 5, 2013
Last verified: July 2013
  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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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: 6 weeks through 18 months ] [ Designated as safety issue: Yes ]
    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:
  • 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: Week 8 and Month 3 ] [ Designated as safety issue: No ]
    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


Enrollment: 2026
Study Start Date: January 2007
Study Completion Date: November 2011
Primary Completion Date: September 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
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074412

Locations
South Africa
CAPRISA Umlazi CRS
Umlazi, KwaZulu-Natal, South Africa
Tanzania
Muhimbili University of Health and Allied Sciences (MUHAS) CRS
Dar es Salaam, Tanzania
Uganda
Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS
Kampala, Mpigi, Uganda
Zimbabwe
Seke North CRS
Chitungwiza, Zimbabwe
St Mary's CRS
Chitungwiza, Zimbabwe
Sponsors and Collaborators
Investigators
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
Results First Received: May 30, 2013
Last Updated: July 5, 2013
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
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 19, 2014