HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission

Abstract

Background: The effects of short-course antiretrovirals given to reduce mother-to-child transmission (MTCT) on temporal patterns of cell-associated HIV-1 RNA and DNA in breast milk are not well defined. Methods: Women in Kenya received short-course zidovudine (ZDV), single-dose nevirapine (sdNVP), combination ZDV/sdNVP or short-course highly active antiretroviral therapy (HAART). Breast milk samples were collected two to three times weekly for 4–6weeks.HIV-1 DNA was quantified b yreal-time PCR.Cell-free and cell associated RNA levels were quantified by the Gen-Probe HIV-1 viral load assay. Results: Cell-free HIV-1 RNA levels in breast milk were significantly suppressed by sdNVP, ZDV/sdNVP or HAART therapy compared with ZDV between day 3 and week 4 postpartum (P0.03). Breast milk HIV-1 DNA levels (infected cell levels) were not significantly different between treatment arms at any timepoint during the 4–6-week follow-up. At 3 weeks postpartum, when the difference in cell-free RNA levels was the greatest comparing HAARTdirectly with ZDV(P¼0.0001),medianlog10 HIV-1 DNA copies per 1106 cells were 2.78, 2.54, 2.69, and 2.31 in the ZDV, sdNVP, ZDV/sdNVP and HAART arms, respectively (P¼0.23). Cell-associated HIV-1 RNA levels were modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P¼0.04), as well as over time according to a linear mixed-effects model. Conclusion: Cell-free and,to a lesser extent,cell-associated HIV-1 RNA levels in breast milk were suppressed by antiretroviral regimens used to prevent MTCT.However,even with HAART, there was no significant reduction in the reservoir of infected cells,which could contribute to breast milk HIV-1 transmission.