ARVs to Prevent Breastmilk HIV:Viral and Immune Responses
Status:
Completed
Trial end date:
2006-04-01
Target enrollment:
Participant gender:
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.