Variation in antiviral immunity and inflammation pathways precedes HIV-1 infection in a high-risk African cohort
Mwikali Kioko, Shaban Mwangi, Lynn Fwambah, Amin S. Hassan, Jason T. Blackard, Philip Bejon, Eduard Sanders, Thumbi Ndung’u, Eunice W. Nduati, Abdirahman I. Abdi
Mwikali Kioko, Shaban Mwangi, Lynn Fwambah, Amin S. Hassan, Jason T. Blackard, Philip Bejon, Eduard Sanders, Thumbi Ndung’u, Eunice W. Nduati, Abdirahman I. Abdi
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Clinical Research and Public Health AIDS/HIV Immunology Infectious disease

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

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).

Authors

Mwikali Kioko, Shaban Mwangi, Lynn Fwambah, Amin S. Hassan, Jason T. Blackard, Philip Bejon, Eduard Sanders, Thumbi Ndung’u, Eunice W. Nduati, Abdirahman I. Abdi

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Figure 1

Schematic representation of our study design.

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Schematic representation of our study design. Three and 6 months prior t...
Three and 6 months prior to HIV infection, samples were selected from a historic high-risk cohort study conducted on the Kenyan coast between 2006 and 2011. Cases were defined as those who tested positive for HIV during follow-up using RT-PCR, p24 antigen, and HIV-1–specific antibody assays. Controls were defined as individuals who remained HIV negative during follow-up; they were matched to the cases based on sex, age, risk group, follow-up duration, and availability of samples.