ARVs to Prevent Breastmilk HIV:Viral and Immune Responses

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.

Timeline

Start

2003-11-03

Primary completion

2005-03

Completion

2006-04

Publications

• Background Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, Njiri F, John-Stewart GC. Independent effects of nevirapine prophylaxis and HIV-1 RNA suppression in breast milk on early perinatal HIV-1 transmission. J Acquir Immune Defic Syndr. 2007 Dec 1;46(4):472-8. doi: 10.1097/qai.0b013e3181594c1c.
• Results Lehman DA, Chung MH, John-Stewart GC, Richardson BA, Kiarie J, Kinuthia J, Overbaugh J. HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. AIDS. 2008 Jul 31;22(12):1475-85. doi: 10.1097/QAD.0b013e328302cc11.
• Results Chung MH, Kiarie JN, Richardson BA, Lehman DA, Overbaugh J, Kinuthia J, Njiri F, John-Stewart GC. Highly active antiretroviral therapy versus zidovudine/nevirapine effects on early breast milk HIV type-1 Rna: a phase II randomized clinical trial. Antivir Ther. 2008;13(6):799-807.
• Results Lehman DA, Chung MH, Mabuka JM, John-Stewart GC, Kiarie J, Kinuthia J, Overbaugh J. Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):522-9. doi: 10.1097/QAI.0b013e3181aa8a22.
• Slyker JA, Richardson B, Chung MH, Atkinson C, Asbjornsdottir KH, Lehman DA, Boeckh M, Emery V, Kiarie J, John-Stewart G. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels. AIDS Res Hum Retroviruses. 2017 Apr;33(4):332-338. doi: 10.1089/AID.2016.0121. Epub 2016 Dec 6.

Drugs

Indications