Breastfeeding, Antiretroviral, and Nutrition Study

Study Overview
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Brief Summary
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This is a comparative clinical trial among HIV-infected women and their infants to determine: the benefit of nutritional supplementation given to women during breastfeeding the benefit and safety of antiretroviral (ARV) medications given either to infants or to their mothers to prevent HIV transmission during breastfeeding the feasibility of exclusive breastfeeding followed by early, rapid breastfeeding cessation

Detailed Description
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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: 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). 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. 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.

Official Title
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HIV Infection and Breastfeeding: Interventions for Maternal and Infant Health

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir
* Drug: Infant nevirapine
* Dietary Supplement: Maternal protein and calorie supplement


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Maternal ARVs & Nutrition Supplement<br>Extended maternal ARVs for prophylaxis (for the infant) & daily nutritional supplement given to the mother | Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir<br>* 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.<br>* Other names: Aluvia tabs (lopinavir 200mg /ritonavir 50mg);Dietary Supplement: Maternal protein and calorie supplement<br>* 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.<br>* Other names: Produced by Nutriset. Daily dose: 2 sachets.;|
| Active Comparator: Infant NVP & Nutrition Supplement<br>Extended infant nevirapine for prophylaxis & daily nutritional supplment given to the mother | Drug: Infant nevirapine<br>* Nevirapine suspension once daily dose. 0-14days: 10mg; 3-18weeks: 20mg; 19-28weeks: 30mg. To 28 weeks while breastfeeding.<br>* Other names: Viramune (Nevirapine) suspension 50mg/5ml;Dietary Supplement: Maternal protein and calorie supplement<br>* 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.<br>* Other names: Produced by Nutriset. Daily dose: 2 sachets.;|
| Active Comparator: Maternal ARVs & No Nutrition Supplement<br>Extended maternal ARVs for prophylaxis (for the infant) & no nutritional supplement given to the mother | Drug: Maternal zidovudine/lamivudine/lopinavir-ritonavir<br>* 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.<br>* Other names: Aluvia tabs (lopinavir 200mg /ritonavir 50mg);|
| Active Comparator: Infant NVP & No Nutrition Supplement<br>Extended infant nevirapine for prophylaxis & no nutritional supplment given to the mother | Drug: Infant nevirapine<br>* Nevirapine suspension once daily dose. 0-14days: 10mg; 3-18weeks: 20mg; 19-28weeks: 30mg. To 28 weeks while breastfeeding.<br>* Other names: Viramune (Nevirapine) suspension 50mg/5ml;|
| Active Comparator: No Drugs & Nutrition Supplement<br>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<br>* 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.<br>* Other names: Produced by Nutriset. Daily dose: 2 sachets.;|
| No Intervention: No Drugs & No Nutrition Supplement<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Clinical trial, breastfeeding, mother-to-child-transmission, nutrition, HIV Seronegativity