Highly Active Antiretroviral Therapy (HAART) versus Zidovudine/Nevirapine Effects on Early Breast Milk HIV-1 RNA: A Phase II Randomized Clinical Trial

Abstract

Background

Defining the effect of antiretroviral regimens on breast milk HIV-1 levels is useful to inform the rational design of strategies to decrease perinatal HIV-1 transmission. Methods

Pregnant HIV-1 seropositive women (CD4 >250 and <500 cells/mm3) electing to breastfeed in Nairobi, Kenya were randomized to HAART (zidovudine, lamivudine, and nevirapine) during pregnancy and 6 months postpartum or to short-course zidovudine plus single-dose nevirapine (ZDV/NVP). Breast milk samples were collected 2-3 times per week in the first month postpartum. Findings

Between November 2003 and April 2006, 444 breast milk samples were collected from 58 randomized women during the first month after delivery. Between 3 and 14 days postpartum, women in the HAART and ZDV/NVP arms had a similar prevalence of undetectable breast milk HIV-1 RNA. From 15 to 28 days postpartum, women in the HAART arm had significantly lower levels of breast milk HIV-1 RNA than women randomized to ZDV/NVP (1.7 log10 copies/ml (limit of detection) vs. > 2.10 log10 copies/ml, P < 0.001). In contrast to breast milk HIV-1 RNA, suppression of plasma HIV-1 RNA during the neonatal period was consistently several log10 greater in the HAART arm compared to the ZDV/NVP arm. Conclusions

HAART resulted in lower breast milk HIV-1 RNA than ZDV/NVP, however, ZDV/NVP yielded comparable breast milk HIV-1 RNA levels in the first 2 weeks postpartum. Breast milk HIV-1 RNA remained suppressed in the ZDV/NVP arm despite increased plasma HIV-1 levels, which may reflect local drug-effects or compartmentalization.