Mucosal Extracellular Vesicles From Semen, Vaginal Fluid, and Breast Milk As an Integrated Antiviral Defense Against Hiv: A Systematic Review Publisher

Summary: Could tiny vesicles help block HIV? Preclinical studies found bodily-fluid vesicles blocked HIV entry or replication; human trials are needed. #HIV #ExtracellularVesicles

Hamdi M ; Ghafourian A ; Dehghan P ; Rahimkhani M ; Gharehdaghi R ; Davoudi M ; Zavvar M ; Bagherieh M ; Afrisham R
Source: Regenerative Engineering and Translational Medicine Published:2026

Abstract

Background and Aims: Extracellular vesicles (EVs) from human reproductive secretions (semen, vaginal fluid, and breast milk) and vesicles from vaginal probiotics have shown promise as antiviral agents. This systematic review examined the anti-HIV effects of these vesicles in in vitro, ex vivo, and in vivo models. Methodology: A search of PubMed, Scopus, and ISI Web of Science was conducted until November 24, 2025, following PRISMA 2020. Only peer-reviewed studies on EVs and their therapeutic effects on HIV infection, replication, and reverse transcription were included. Study quality was assessed using QUIN for cell-based studies and SYRCLE Risk of Bias for animal studies. Results: Fifteen studies met the criteria. Semen-derived EVs inhibited HIV replication by 50–80%, targeting early post-entry stages. Vaginal fluid-derived EVs blocked viral entry and supported epithelial barrier function. Breast milk-derived EVs, enriched with Mucin 1, reduced HIV-1 BaL infection in dendritic cells and prevented viral transmission to CD4 + T cells, which is consistent with low rates of postnatal HIV transmission observed in antiretroviral-treated breastfed infants. Vesicles from vaginal gram-positive microbiota suppressed HIV replication, viral entry, Gag transcription, and p24 production. EVs from epithelial and immune cells delivered interferon-stimulated genes and microRNAs. Genetically engineered EVs loaded with miR-143 or CRISPR-based repressors showed enhanced anti-HIV activity. Conclusion: While these findings demonstrate substantial antiviral activity in preclinical models, all evidence to date remains preclinical. Successful translation would require standardized GMP-compliant EV production, rigorous safety evaluation, and carefully designed clinical trials. Topical microbicide formulations may represent one potential future application worth exploring in high-risk populations, though this remains speculative pending further preclinical validation, safety data, and regulatory guidance. Lay Summary: Extracellular vesicles from human bodily fluids show strong potential in fighting HIV. Research found that vesicles from semen, vaginal fluid, and breast milk can block the virus from entering cells, reduce its replication, and strengthen protective barriers. Engineered versions of these particles are even more powerful. © The Author(s), under exclusive licence to The Regenerative Engineering Society 2026.