Variation in antiviral immunity and inflammation pathways precedes HIV-1 infection in a high-risk African cohort

Journal article

Background

Susceptibility to human immunodeficiency virus type 1 (HIV-1) infection varies between individuals, but the biological determinants of acquisition risk remain poorly defined.

Methods

We conducted a case-control study nested within a high-risk cohort in Kenya. We compared the plasma extracellular RNA collected before HIV-1 acquisition with matched uninfected controls to identify immunological processes linked to infection risk.

Results

Individuals who later acquired HIV-1 exhibited upregulation of immune processes that facilitate viral infection, including T cell suppression, type II interferon and Th2 immune responses. In contrast, processes associated with antiviral defence and tissue repair, such as neutrophil and natural killer cell responses, type I interferon responses, wound healing, and angiogenesis, were downregulated.

Conclusion

These findings highlight dampened antiviral immunity prior to exposure as a correlate of increased risk for subsequent HIV-1 acquisition.

Trial numbers

Not applicable.

Funding

This work was supported by a Wellcome Trust Award (209289/Z/17/Z) and the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) through the DELTAS Africa programme [Del-22-007], supported by the Science for Africa Foundation, Wellcome Trust, the UK Foreign, Commonwealth & Development Office, and the European Union. Additional support was provided by the Bill & Melinda Gates Foundation, Gilead Sciences Inc., Aidsfonds, and the Ragon Institute of Mass General, MIT, and Harvard. The cohort study was supported by PEPFAR through USAID. The views expressed are those of the authors.

Authors: Kioko, M; Mwangi, S; Fwambah, L; Hassan, AS; Blackard, JT

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Society for Clinical Investigation
• Journal: The Journal of Clinical Investigation
• Pages: e195172
• Publication date: 2026-02-12
• DOI: 10.1172/jci195172
• EISSN: 1558-8238
• ISSN: 0021-9738
• Language: English
• Keywords: Immunity; Cohort; Cohort study; Excellence; Commonwealth; Inflammation; Work (physics)