Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	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)
ClinicalTrials.gov Identifier:	NCT00074412

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 III

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Breast Feeding HIV/AIDS

Drug Information available for: Nevirapine

U.S. FDA Resources

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: Throughout study ] [ Designated as safety issue: Yes ]

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: 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

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

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

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

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)

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:

Click here for more information about nevirapine This link exits the ClinicalTrials.gov site

Click here for more information about HIV and pregnancy This link exits the ClinicalTrials.gov site

Click here for more information on after birth care for HIV positive women and their babies This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Jackson JB, Musoke P, Fleming T, Guay LA, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Owor M, Ducar C, Deseyve M, Mwatha A, Emel L, Duefield C, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Gigliotti M, Bray D, Mmiro F. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-68.

Mitchla Z, Sharland M. Current treatment options to prevent perinatal transmission of HIV. Expert Opin Pharmacother. 2000 Jan;1(2):239-48. Review.

Mofenson LM. Advances in the prevention of vertical transmission of human immunodeficiency virus. Semin Pediatr Infect Dis. 2003 Oct;14(4):295-308. Review.

Piwoz EG, Ross J, Humphrey J. Human immunodeficiency virus transmission during breastfeeding: knowledge, gaps, and challenges for the future. Adv Exp Med Biol. 2004;554:195-210. Review.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Coovadia HM, Brown ER, Fowler MG, Chipato T, Moodley D, Manji K, Musoke P, Stranix-Chibanda L, Chetty V, Fawzi W, Nakabiito C, Msweli L, Kisenge R, Guay L, Mwatha A, Lynn DJ, Eshleman SH, Richardson P, George K, Andrew P, Mofenson LM, Zwerski S, Maldonado Y; HPTN 046 protocol team. Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Jan 21;379(9812):221-8. Epub 2011 Dec 22.

Aizire J, Fowler MG, Wang J, Shetty AK, Stranix-Chibanda L, Kamateeka M, Brown ER, Bolton SG, Musoke PM, Coovadia H. Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated. AIDS. 2012 Jan 28;26(3):325-33.

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 February 13, 2012