Dynamics of the blood plasma proteome during hyperacute HIV-1 infection

HIV-1 remains incurable and there is no effective vaccine towards the infection. A main challenge for this is the lack of a holistic understanding of the myriad of complex virus-host interactions during hyperacute HIV-1 infection (hAHI), and how these contribute to tissue damage and pathogenesis. Here, 1293 blood plasma proteins were quantified from 157 linked plasma samples collected before, during, and after hAHI of 54 volunteers from four sub-Saharan African countries. Six distinct longitudinal expression profiles were identified, of which four demonstrated a consistent decrease in protein levels following HIV-1 infection. Differentially expressed proteins were involved in inflammation, innate immunity, cell motility, and actin cytoskeleton reorganisation. Specifically, decreased levels of Zyxin, Secretoglobin family 1A member 1, and Pro-platelet basic protein were associated with acute retroviral syndrome; Rho GTPase activating protein 18, Annexin A1, and Lipopolysaccharide binding protein with viral load; and Hepsin, Protein kinase C beta, and Integrin subunit beta 3 with disease progression. This is the first holistic characterisation of within-patient blood plasma proteome dynamics during the first weeks of HIV-1 infection and presents multiple potential blood biomarkers and targets for prophylactic and therapeutic HIV-1 interventions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the generous support of the American people through the United States Agency for International Development (USAID). The contents are the responsibility of the study authors and do not necessarily reflect the views of USAID, the National Institutes of Health (NIH), or the US government. This work was also supported by funding from the Swedish Research Council (grant numbers 2016-01417 and 2020-06262 to J.E) and the Swedish Society for Medical Research (grant number SA-2016 to J.E). The authors are also grateful for the support of the Sub-Saharan African Network for TB/HIV-1 Research Excellence (SANTHE), a DELTAS Africa Initiative (grant number DEL-15-006 to A.S.H). with support by the Wellcome Trust (grant number 107752/Z/15/Z), the UK Foreign, Commonwealth & Development Office, through the Developing Excellence in Leadership, Training and Science in Africa (DELTAS Africa) programme. J.N. was funded by the Swedish Research Council (grant numbers 2016-01417 and 2020-06262) and the Medical Faculty at Lund University. A. S. H. was supported by a training fellowship from the Wellcome Trust (209294/Z/17/Z). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the University of KwaZulu-Natal and the institutional review board of Massachusetts General Hospital, Kenya Medical Research Institute Ethical Review Committee, the Kenyatta National Hospital Ethical Review Committee of the University of Nairobi, the Rwanda National Ethics Committee, the Uganda Virus Research Institute Science and Ethics Committee, the Uganda National Council of Science and Technology, the University of Cape Town Health Science Research and Ethics Committee, the University of Zambia Research Ethics Committee, the Bio-Medical Research Ethics Committee at the University of KwaZulu Natal, and the Emory University Institutional Review Board gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript