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

Authors

• Mwikali Kioko, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kenya
• Shaban Mwangi, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kenya
• Lynn Fwambah, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kenya
• Amin Hassan, Aga Khan UniversityFollow
• Jason Blackard, University of Cincinnati College of Medicine, USA
• Philip Bejon, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kenya
• Eduard Sanders, University of Oxford, UK
• Thumbi Ndung’u, Africa Health Research Institute, South Africa.
• Eunice Nduati, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kenya
• Abdirahman Abdi, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kenya

Document Type

Article

Department

Institute for Human Development

Abstract

BACKGROUND. Susceptibility to 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 that from matched uninfected individuals acting as 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 and type II IFN and Th2 immune responses. In contrast, processes associated with antiviral defence and tissue repair, such as neutrophil and NK cell responses, type I IFN 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.

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 Developing Excellence in Leadership, Training and Science in Africa (DELTAS Africa) programme (Del-22-007), which is supported by the Science for Africa Foundation; Wellcome Trust; the UK Foreign, Commonwealth & Development Office; the European Union; and the Ragon Institute of Mass General, MIT, and Harvard. The Bill & Melinda Gates Foundation, Gilead Sciences Inc., and Aidsfonds provided additional support. The US President’s Emergency Plan for AIDS Relief (PEPFAR) supported the cohort study through the US Agency for International Development (USAID).

Publication (Name of Journal)

The Journal of clinical investigation

DOI

https://doi.org/10.1172/JCI195172

Recommended Citation

Kioko, M., Mwangi, S., Fwambah, L., Hassan, A., Blackard, J., Bejon, P., Sanders, E., Ndung’u, T., Nduati, E., Abdi, A. (2026). Variation in antiviral immunity and inflammation pathways precedes HIV-1 infection in a high-risk African cohort. The Journal of clinical investigation, 136(7), 1-12.
Available at: https://ecommons.aku.edu/eastafrica_ihd/260

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.