ARVs to Prevent Breastmilk HIV:Viral and Immune Responses

• Status: Completed
• Trial end date: 2006-04-01
• Target enrollment: 0
• Participant gender: Female

Summary

Identifying new approaches for preventing breastmilk transmission of HIV-1 is an important research priority. To this end, clinical trials are underway to evaluate the efficacy of HAART (zidovudine, lamivudine, nevirapine) during late pregnancy/lactation versus zidovudine/nevirapine peripartum for prevention of breastmilk HIV-1 transmission. It is important to understand the mechanism of effect of these antiretroviral (ARV) strategies on prevention of breastmilk HIV-1 transmission.

This phase II trial will compare HAART vs peripartum zidovudine/nevirapine for effect on breastmilk HIV-1, breastmilk HIV-1 specific immune responses, and infant HIV-1 specific immune responses.

100 pregnant HIV-1 seropositive women in Nairobi with CD4 counts between 200 to 500 who have chosen to breastfeed will receive either ARV regimen. Mother-infant pairs will be followed for 1 year after delivery. Home visits will be conducted in the first month (~10 visits) to collect 2-5 mls of breastmilk per visit. Mother-infant pairs will be seen in the study clinic with maternal blood and breastmilk and infant blood collected at months 1, 3, and 6 for HIV-1 and HIV-1 Elispot assays. Breastmilk HIV-1 RNA and DNA levels will be quantified in Dr. Overbaugh's laboratory in Seattle and Elispot assays conducted in Nairobi with validation of a subset in Dr. Rowland-Jones laboratory in Oxford. Viral loads, decay curves, half-life, and re-population following ARV cessation will be estimated for each regimen and regimens compared. These studies will provide insight into the viral and immune responses to ARV regimens proposed for prevention of breastfeeding HIV-1 transmission and will be important for rational design of future interventions. After taking into account, estimated loss to follow-up, the targeted sample size with outcome data was 80 women, 40 in each trial arm, estimating undetectable breast milk HIV-1 RNA levels in the HAART arm and median breast milk HIV-1 RNA levels of 3.0 log10 in women receiving ZDV/NVP.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborator: Elizabeth Glaser Pediatric AIDS Foundation
• Treatments: Nevirapine; Zidovudine

Criteria

Inclusion Criteria:

• The subject population is recruited from Mathare North Clinic in Nairobi, Kenya where voluntary HIV-1 counseling and testing is offered to pregnant women

• Pregnant women who test positive for HIV-1 antibody are eligible for the study if they are over 18 years of age

• At less than 32 weeks' gestation

• Have never previously been exposed to antiretroviral medications

• Agree to serial maternal blood

• Breast milk

• Infant blood draws

• Plan to live in Nairobi for at least a year after delivery.

Exclusion Criteria:

• CD4 >500 or <200

• Not planning to live in Nairobi after delivery

• Not planning to breastfeed.