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Breastfeeding, Antiretroviral, and Nutrition Study

This study has been completed.
Sponsor:
Collaborators:
University of North Carolina, Chapel Hill
Kamuzu Central Hospital, Lilongwe, Malawi
Information provided by:
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00164736
First received: September 13, 2005
Last updated: April 22, 2010
Last verified: April 2010
History of Changes
  Purpose

This is a comparative clinical trial among HIV-infected women and their infants to determine:

  1. the benefit of nutritional supplementation given to women during breastfeeding
  2. the benefit and safety of antiretroviral (ARV) medications given either to infants or to their mothers to prevent HIV transmission during breastfeeding
  3. the feasibility of exclusive breastfeeding followed by early, rapid breastfeeding cessation

Condition Intervention Phase
HIV Infections
 Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir
Drug: Infant nevirapine
Dietary Supplement: Maternal protein and calorie supplement
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: HIV Infection and Breastfeeding: Interventions for Maternal and Infant Health

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Postpartum weight loss between delivery and 28 weeks [ Time Frame: between delivery and 28 weeks ] [ Designated as safety issue: Yes ]
  • Infant HIV status at 28 weeks. (Infants found to have HIV at birth or 2 weeks after delivery will have been disenrolled.) [ Time Frame: birth to 28 weeks ] [ Designated as safety issue: No ]
  • Exclusive breastfeeding and breastfeeding cessation by 28 weeks [ Time Frame: birth to 28 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of exclusive breastfeeding [ Time Frame: birth to 28 weeks ] [ Designated as safety issue: No ]
  • Infant HIV status through 48 weeks [ Time Frame: birth to 48 weeks ] [ Designated as safety issue: No ]
  • Maternal adherence to ARV, maternal CD4 count, and clinical assessment of opportunistic infection status through 48 weeks [ Time Frame: delivery to 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 2369
Study Start Date: March 2004
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Maternal ARVs & Nutrition Supplement
Extended maternal ARVs for prophylaxis (for the infant) & daily nutritional supplement given to the mother
 Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir
Total daily dose: zidovudine 600mg, lamivudine 300mg, (taken as Combivir 1 tab twice a day with food). Lopinavir/ritonavir 400/100mg (taken as 2 tabs twice a day). Commencing after delivery and through to 28 weeks.
Other Names:
  • Combivir tabs (zidovudine 300mg and lamivudine 150mg)
  • Aluvia tabs (lopinavir 200mg /ritonavir 50mg)
Dietary Supplement: Maternal protein and calorie supplement
High energy, nutrient-dense, micronutrient fortified nutritional supplement. Daily: Energy 700kcal, Protein 20g, 100% of recommended dietary allowance for all micronutrients during the 6 months of lactation. Vitamin A is excluded.
Other Name: Produced by Nutriset. Daily dose: 2 sachets.
Active Comparator: Infant NVP & Nutrition Supplement
Extended infant nevirapine for prophylaxis & daily nutritional supplment given to the mother
 Drug: Infant nevirapine

Nevirapine suspension once daily dose. 0-14days: 10mg; 3-18weeks: 20mg; 19-28weeks: 30mg.

To 28 weeks while breastfeeding.

Other Name: Viramune (Nevirapine) suspension 50mg/5ml
Dietary Supplement: Maternal protein and calorie supplement
High energy, nutrient-dense, micronutrient fortified nutritional supplement. Daily: Energy 700kcal, Protein 20g, 100% of recommended dietary allowance for all micronutrients during the 6 months of lactation. Vitamin A is excluded.
Other Name: Produced by Nutriset. Daily dose: 2 sachets.
Active Comparator: Maternal ARVs & No Nutrition Supplement
Extended maternal ARVs for prophylaxis (for the infant) & no nutritional supplement given to the mother
 Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir
Total daily dose: zidovudine 600mg, lamivudine 300mg, (taken as Combivir 1 tab twice a day with food). Lopinavir/ritonavir 400/100mg (taken as 2 tabs twice a day). Commencing after delivery and through to 28 weeks.
Other Names:
  • Combivir tabs (zidovudine 300mg and lamivudine 150mg)
  • Aluvia tabs (lopinavir 200mg /ritonavir 50mg)
Active Comparator: Infant NVP & No Nutrition Supplement
Extended infant nevirapine for prophylaxis & no nutritional supplment given to the mother
 Drug: Infant nevirapine

Nevirapine suspension once daily dose. 0-14days: 10mg; 3-18weeks: 20mg; 19-28weeks: 30mg.

To 28 weeks while breastfeeding.

Other Name: Viramune (Nevirapine) suspension 50mg/5ml
Active Comparator: No Drugs & Nutrition Supplement

No extended maternal ARV prophylaxis nor infant nevirapine prophylaxis & daily nutritional supplement given to the mother.

Note: As of March 2008, the third arm of the antiretroviral intervention, in which neither mother nor infant received drugs beyond enhanced standard of care, was stopped based on recommendations of a Data and Safety Monitoring Board review of interim efficacy results and safety data after 77% participants had received treatment assignment.

 Dietary Supplement: Maternal protein and calorie supplement
High energy, nutrient-dense, micronutrient fortified nutritional supplement. Daily: Energy 700kcal, Protein 20g, 100% of recommended dietary allowance for all micronutrients during the 6 months of lactation. Vitamin A is excluded.
Other Name: Produced by Nutriset. Daily dose: 2 sachets.
No Intervention: No Drugs & No Nutrition Supplement

No extended maternal ARV prophylaxis nor infant nevirapine prophylaxis & no nutritional supplement given to the mother.

Note: As of March 2008, the third arm of the antiretroviral intervention, in which neither mother nor infant received drugs beyond enhanced standard of care, was stopped based on recommendations of a Data and Safety Monitoring Board review of interim efficacy results and safety data after 77% participants had received treatment assignment.

Detailed Description:

This study addresses the complex issues of HIV related maternal morbidity, mortality, and postnatal HIV transmission during breastfeeding and weaning in resource-poor countries. Objectives include assessment of mortality and morbidity among HIV-infected women; evaluation of interventions to reduce HIV transmission to infants exposed by breast milk; and assessment of early weaning as a risk-reduction strategy for infants of HIV-infected mothers.

The study will evaluate the following:

  1. The efficacy of a high-density caloric/micronutrient nutritional supplement given to HIV-infected women who breastfeed in preventing maternal depletion (weight loss and micronutrient status).
  2. The safety and efficacy of maternal or infant antiretroviral regimens, taken for up to 6 months during breastfeeding, in reducing infant HIV infection rates at 48 weeks.
  3. The feasibility of exclusive breastfeeding for 6 months followed by rapid weaning.

Additional study objectives are to evaluate the feasibility of delivering these interventions in resource poor settings and to identify maternal, infant, and virologic factors associated with HIV transmission during breastfeeding.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Recruitment and primary eligibility criteria:

  • Age > 14 years.
  • Ability to give informed assent or consent.
  • Evidence of HIV infection, as documented by 2 positive ELISA antibody tests; or 1 positive ELISA, and 1 Western Blot; or 2 separate concurrent rapid tests.
  • Currently pregnant (with a single or multiple fetuses).
  • Gestation < 30 weeks at referral from 'Call to Action' Program
  • No serious current complications of pregnancy.
  • Intention to breastfeed.
  • Intention to deliver at the institution at which the study is based.
  • Not previously enrolled in this study for an earlier pregnancy.
  • Other than HIV, no active serious infection, such as tuberculosis or other potentially serious illnesses.
  • No previous use of antiretrovirals including the HIVNET 012 regimen.
  • Mother's CD4 count > 250 cells/uL determined in the antenatal clinic.
  • Mother's ALT < 2.5 x ULN (upper limit of normal) determined in the antenatal clinic

Secondary eligibility criteria and treatment assignment:

  • Mother who delivers outside of the institution at which the study is based must present with her infant to the study site within 36 hours of delivery.
  • Mother accepts nevirapine and zidovudine+lamivudine 7-day regimen for herself and her infant.
  • Infant birth weight > 2000 g.
  • No severe congenital malformations or other condition(s) not compatible with life.
  • Based on clinical assessment, no maternal condition which would preclude the start of the study intervention.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00164736

Locations
Malawi
Kamuzu Central Hospital, Bottom Hospital
Lilongwe, Malawi
Sponsors and Collaborators
Centers for Disease Control and Prevention
University of North Carolina, Chapel Hill
Kamuzu Central Hospital, Lilongwe, Malawi
Investigators
Study Chair: Charles van der Horst, MD University of North Carolina, Chapel Hill
Principal Investigator: Denise J Jamieson, MD, MPH CDC, Atlanta, GA
Principal Investigator: Peter Kazembe, MB ChB Kamuzu Central Hospital, Lilongwe, Malawi
  More Information

No publications provided by Centers for Disease Control and Prevention

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

Responsible Party: Dr. Denise Jamieson, CDC
ClinicalTrials.gov Identifier: NCT00164736     History of Changes
Other Study ID Numbers: CDC-NCCDPHP-3946, U48CCU409660, PA 04003 SIP 26-04
Study First Received: September 13, 2005
Last Updated: April 22, 2010
Health Authority: United States: Federal Government
United States: Institutional Review Board
Malawi: National Health Sciences Research Committee

Keywords provided by Centers for Disease Control and Prevention:
HIV
Clinical trial
breastfeeding
 mother-to-child-transmission
nutrition
HIV Seronegativity

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
Zidovudine
Nevirapine
Lamivudine
Lamivudine, zidovudine drug combination
 Ritonavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on March 14, 2013