Breastfeeding, Antiretroviral, and Nutrition Study

NCT00164736 | Completed Phase 3 DMC

• 3 other identifiers: CDC-NCCDPHP-3946U48CCU409660PA 04003 SIP 26-04
• Study Type: interventional
• Target: 2,369
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Conditions

HIV Infections

Keywords

HIV; Clinical trial; breastfeeding; mother-to-child-transmission; nutrition; HIV Seronegativity

Outcome Measures

Primary Outcomes (3)

• Postpartum weight loss between delivery and 28 weeks

  between delivery and 28 weeks

• Infant HIV status at 28 weeks. (Infants found to have HIV at birth or 2 weeks after delivery will have been disenrolled.)

  birth to 28 weeks

• Exclusive breastfeeding and breastfeeding cessation by 28 weeks

  birth to 28 weeks

Secondary Outcomes (3)

• Duration of exclusive breastfeeding

  birth to 28 weeks

• Infant HIV status through 48 weeks

  birth to 48 weeks

• Maternal adherence to ARV, maternal CD4 count, and clinical assessment of opportunistic infection status through 48 weeks

  delivery to 48 weeks

Study Arms (6)

Maternal ARVs & Nutrition Supplement

ACTIVE COMPARATOR

Extended maternal ARVs for prophylaxis (for the infant) \& daily nutritional supplement given to the mother

Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir; Dietary Supplement: Maternal protein and calorie supplement

Infant NVP & Nutrition Supplement

ACTIVE COMPARATOR

Extended infant nevirapine for prophylaxis \& daily nutritional supplment given to the mother

Drug: Infant nevirapine; Dietary Supplement: Maternal protein and calorie supplement

Maternal ARVs & No Nutrition Supplement

ACTIVE COMPARATOR

Extended maternal ARVs for prophylaxis (for the infant) \& no nutritional supplement given to the mother

Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir

Infant NVP & No Nutrition Supplement

ACTIVE COMPARATOR

Extended infant nevirapine for prophylaxis \& no nutritional supplment given to the mother

Drug: Infant nevirapine

No Drugs & Nutrition Supplement

ACTIVE COMPARATOR

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

No Drugs & No Nutrition Supplement

NO INTERVENTION

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.

Interventions

Maternal zidovudine/lamivudine/lopinavir-ritonavir DRUG

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.

Also known as: Combivir tabs (zidovudine 300mg and lamivudine 150mg), Aluvia tabs (lopinavir 200mg /ritonavir 50mg)

Maternal ARVs & No Nutrition Supplement; Maternal ARVs & Nutrition Supplement

Infant nevirapine DRUG

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

Also known as: Viramune (Nevirapine) suspension 50mg/5ml

Infant NVP & No Nutrition Supplement; Infant NVP & Nutrition Supplement

Maternal protein and calorie supplement DIETARY_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.

Also known as: Produced by Nutriset. Daily dose: 2 sachets.

Infant NVP & Nutrition Supplement; Maternal ARVs & Nutrition Supplement; No Drugs & Nutrition Supplement

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• University of North Carolina, Chapel Hill: collaborator
• Kamuzu Central Hospital: collaborator

Study Sites (1)

Kamuzu Central Hospital, Bottom Hospital

Lilongwe, Malawi

Location

Related Publications (9)

• Flax VL, Adair LS, Allen LH, Shahab-Ferdows S, Hampel D, Chasela CS, Tegha G, Daza EJ, Corbett A, Davis NL, Kamwendo D, Kourtis AP, van der Horst CM, Jamieson DJ, Bentley ME; BAN Study Team. Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women. J Nutr. 2015 Aug;145(8):1950-7. doi: 10.3945/jn.115.212290. Epub 2015 Jul 8.

  PMID: 26156797 DERIVED

• Widen EM, Bentley ME, Chasela CS, Kayira D, Flax VL, Kourtis AP, Ellington SR, Kacheche Z, Tegha G, Jamieson DJ, van der Horst CM, Allen LH, Shahab-Ferdows S, Adair LS; BAN Study Team. Antiretroviral Treatment Is Associated With Iron Deficiency in HIV-Infected Malawian Women That Is Mitigated With Supplementation, but Is Not Associated With Infant Iron Deficiency During 24 Weeks of Exclusive Breastfeeding. J Acquir Immune Defic Syndr. 2015 Jul 1;69(3):319-28. doi: 10.1097/QAI.0000000000000588.

  PMID: 25723140 DERIVED

• Flax VL, Bentley ME, Combs GF Jr, Chasela CS, Kayira D, Tegha G, Kamwendo D, Daza EJ, Fokar A, Kourtis AP, Jamieson DJ, van der Horst CM, Adair LS. Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study. Am J Clin Nutr. 2014 Apr;99(4):950-6. doi: 10.3945/ajcn.113.073833. Epub 2014 Feb 5.

  PMID: 24500152 DERIVED

• Widen EM, Bentley ME, Kayira D, Chasela CS, Daza EJ, Kacheche ZK, Tegha G, Jamieson DJ, Kourtis AP, van der Horst CM, Allen LH, Shahab-Ferdows S, Adair LS; BAN Study Team. Changes in soluble transferrin receptor and hemoglobin concentrations in Malawian mothers are associated with those values in their exclusively breastfed, HIV-exposed infants. J Nutr. 2014 Mar;144(3):367-74. doi: 10.3945/jn.113.177915. Epub 2013 Dec 31.

  PMID: 24381222 DERIVED

• Widen EM, Bentley ME, Kayira D, Chasela CS, Jamieson DJ, Tembo M, Soko A, Kourtis AP, Flax VL, Ellington SR, van der Horst CM, Adair LS; BAN Study team. Maternal weight loss during exclusive breastfeeding is associated with reduced weight and length gain in daughters of HIV-infected Malawian women. J Nutr. 2013 Jul;143(7):1168-75. doi: 10.3945/jn.112.171751. Epub 2013 May 22.

  PMID: 23700341 DERIVED

• Flax VL, Bentley ME, Chasela CS, Kayira D, Hudgens MG, Kacheche KZ, Chavula C, Kourtis AP, Jamieson DJ, van der Horst CM, Adair LS. Lipid-based nutrient supplements are feasible as a breastmilk replacement for HIV-exposed infants from 24 to 48 weeks of age. J Nutr. 2013 May;143(5):701-7. doi: 10.3945/jn.112.168245. Epub 2013 Mar 6.

  PMID: 23468553 DERIVED

• Flax VL, Bentley ME, Chasela CS, Kayira D, Hudgens MG, Knight RJ, Soko A, Jamieson DJ, van der Horst CM, Adair LS. Use of lipid-based nutrient supplements by HIV-infected Malawian women during lactation has no effect on infant growth from 0 to 24 weeks. J Nutr. 2012 Jul;142(7):1350-6. doi: 10.3945/jn.111.155598. Epub 2012 May 30.

  PMID: 22649265 DERIVED

• Jamieson DJ, Chasela CS, Hudgens MG, King CC, Kourtis AP, Kayira D, Hosseinipour MC, Kamwendo DD, Ellington SR, Wiener JB, Fiscus SA, Tegha G, Mofolo IA, Sichali DS, Adair LS, Knight RJ, Martinson F, Kacheche Z, Soko A, Hoffman I, van der Horst C; BAN study team. Maternal and infant antiretroviral regimens to prevent postnatal HIV-1 transmission: 48-week follow-up of the BAN randomised controlled trial. Lancet. 2012 Jun 30;379(9835):2449-2458. doi: 10.1016/S0140-6736(12)60321-3. Epub 2012 Apr 26.

  PMID: 22541418 DERIVED

• Chasela CS, Hudgens MG, Jamieson DJ, Kayira D, Hosseinipour MC, Kourtis AP, Martinson F, Tegha G, Knight RJ, Ahmed YI, Kamwendo DD, Hoffman IF, Ellington SR, Kacheche Z, Soko A, Wiener JB, Fiscus SA, Kazembe P, Mofolo IA, Chigwenembe M, Sichali DS, van der Horst CM; BAN Study Group. Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med. 2010 Jun 17;362(24):2271-81. doi: 10.1056/NEJMoa0911486.

  PMID: 20554982 DERIVED

MeSH Terms

Conditions

HIV Infections; Breast Feeding

Interventions

Zidovudine; Lamivudine; Lopinavir; Ritonavir; Nevirapine; Suspensions

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidinones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Pyridines; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Charles van der Horst, MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• Denise J Jamieson, MD, MPH

  CDC, Atlanta, GA

  PRINCIPAL INVESTIGATOR

• Peter Kazembe, MB ChB

  Kamuzu Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: FED

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 14, 2005
• Study Start: March 1, 2004
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: April 23, 2010

Record last verified: 2010-04

Locations

MA (1)