Innate Factors in Human Breast Milk Inhibit Cell-Free HIV-1 but Not Cell-Associated HIV-1 Infection of CD4+ Cells

Background: Transmission of HIV from mother to child through breast-feeding remains a global health challenge, particularly in developing countries. Breast milk from an HIV infected women may contain both cell-free HIV-1 and cell-associated virus; however, the impact of human breast milk on HIV infection and replication in CD4(+) cells remain poorly understood. Objectives: In the present study, we evaluated the effects of breast milk in vitro on infection of CD4(+) cells with cell-free HIV-1, including effects on HIV-1 receptor expression, reverse transcription, integration, and viral transcription. Additionally, we evaluated the ability of breast milk to inhibit cell-associated transmission of HIV-1 from infected CD4(+) T lymphocytes. Results: Our results demonstrate that breast milk potently inhibits infection with cell-free HTV-1 in vitro independently of viral tropism and significantly decreases HIV-1 reverse transcription and integration in CD4(+) cells. However, the inhibitory effect of breast milk on HIV-1 infection of CD4(+) cells was lost during extended culture, and direct coculture of HIV infected CD4(+) T lymphocytes with susceptible target cells revealed that breast milk was ineffective at blocking cell-associated HIV-1 infection. Conclusions: Our findings suggest that breast milk may provide a protective function against cell-free HIV-1 but may be less effective at blocking infection by cell-associated virus.