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.
Kioko et al. (Thu,) studied this question.