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Clinical Research and Public HealthIn-Press PreviewAIDS/HIVImmunologyInfectious disease Open Access | 10.1172/JCI195172

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

Mwikali Kioko,1 Shaban Mwangi,1 Lynn Fwambah,1 Amin S. Hassan,1 Jason T. Blackard,2 Philip Bejon,1 Eduard J. Sanders,3 Thumbi Ndung'u,4 Eunice W. Nduati,1 and Abdirahman I. Abdi1

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Kioko, M. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Mwangi, S. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Fwambah, L. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Hassan, A. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Blackard, J. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Bejon, P. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Sanders, E. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Ndung'u, T. in: PubMed | Google Scholar |

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Nduati, E. in: PubMed | Google Scholar

1Bioscience Department, Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya

2Division of Gastroenterology & Hepatology, University of Cincinnati College of Medicine, Cincinnati, United States of America

3The Aurum Institute, Johannesburg, South Africa

4Africa Health Research Institute, Durban, South Africa

Find articles by Abdi, A. in: PubMed | Google Scholar

Published February 12, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI195172.
Copyright © 2026, Kioko et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 12, 2026 - Version history
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Abstract

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.

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  • Version 1 (February 12, 2026): In-Press Preview
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