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

Lehman, Dara Aa,c; Chung, Michael Hd; John-Stewart, Grace Cd,e; Richardson, Barbra Ab,f; Kiarie, Jamesg; Kinuthia, Johng; Overbaugh, Juliea,b

doi: 10.1097/QAD.0b013e328302cc11
Clinical Science

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 4–6 weeks. HIV-1 DNA was quantified by real-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 HAART directly with ZDV (P = 0.0001), median log10 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 (P = 0.23). Cell-associated HIV-1 RNA levels were modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P = 0.04), 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.

aDivision of Human Biology, USA

bDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, USA

cDepartment of Molecular and Cellular Biology, USA

dDepartment of Medicine, USA

eDepartment of Epidemiology, USA

fDepartment of Biostatistics, University of Washington, Seattle, Washington, USA

gDepartment of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya.

Received 15 January, 2008

Revised 17 March, 2008

Accepted 19 March, 2008

Correspondence to Julie Overbaugh, Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Mailstop C3-168, Seattle, WA 98109-1024, USA. E-mail:

© 2008 Lippincott Williams & Wilkins, Inc.