Human Immunodeficiency Virus and Breastfeeding: Clinical Considerations and Mechanisms of Transmission in the Modern Era of Combined Antiretroviral Therapy

Abstract

Combined antiretroviral therapy has significantly reduced perinatal human immunodeficiency virus (HIV) transmission risk through breastfeeding, prompting shifts in clinical guidance to support breastfeeding for women with HIV who have sustained viral suppression. This review examines the current evidence on HIV transmission via breast milk, including risk factors, mechanisms, and risk reduction strategies to inform patient-centered and evidence-driven clinical care.

Keywords: Antiretroviral therapy (ART); Breastfeeding; HIV; Risk reduction.

Figure 1.

Risk factors for infant HIV transmission through breastfeeding. (A) Elevated maternal plasma viral load (PVL) and diminished CD4 T-cell counts increase risk of BMT. (B) Breast milk viral load (BMVL) including cell-free and cell-associated HIV are associated with increased risk of BMT.^- (C) Longitudinal analyses have demonstrated higher BMVLs in the first few weeks of breast feeding, possibly related to the increased cellularity of colostrum and early lactation.^, However, cumulative exposure is also an important risk factor^,,. (D) Mixed breastfeeding (MBF) has been consistently shown to increase transmission risk in the pre-cART era.^- Figure Created with BioRender.com

Figure 2.

Maternal and infant immune factors that impact postnatal HIV transmission through breast milk. (A) The mammary epithelium prevents HIV entry, maintaining at least a 100-fold lower HIV RNA level compared to plasma. (B) Breast milk contains inhibitory factors, including innate components (lactoferrins, homeostatic cytokines, and mucins) that may protect against cell free HIV replication.^- Pro-inflammatory cytokine profiles (TNF, IL-6, IL-8 and RANTES) are associated with increased risk for BMT.^, HIV-specific cytotoxic T lymphocytes (CTL), IgA and IgG antibodies affect BMT. (C) Disruption of the infant gut interface enables HIV to traverse the epithelial layer, leading to microbiota disturbance and allowing the virus to establish infection in CD4+CCR5+ T cells. Figure Created with BioRender.com