A Stronger Innate Immune Response During Hyperacute Human Immunodeficiency Virus Type 1 (HIV-1) Infection Is Associated With Acute Retroviral Syndrome
Year: 2021
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n = 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciab139
Authors: Amin S Hassan, Jonathan Hare, Kamini Gounder, Jamirah Nazziwa, Sara Karlson, Linnéa Olsson, Claire Streatfield, Anatoli Kamali, Etienne Karita, William Kilembe, Matt A Price, Persephone Borrow, Per Björkman, Pontiano Kaleebu, Susan Allen, Eric Hunter, Thumbi Ndung’u, Jill Gilmour, Sarah Rowland-Jones, Joakim Esbjörnsson, Eduard J Sanders
Institutions: Lund University, Kenya Medical Research Institute, KEMRI-Wellcome Trust Research Programme, International AIDS Vaccine Initiative, Imperial College London, Africa Health Research Institute, University of KwaZulu-Natal, Helsingborgs lasarett, Rwanda Zambia HIV Research Group, University of California, San Francisco, University of Oxford, London School of Hygiene & Tropical Medicine, MRC/UVRI & LSHTM Uganda Research Unit, Medical Research Council, Uganda Virus Research Institute, Emory University, Ragon Institute of MGH, MIT and Harvard, Max Planck Institute for Infection Biology, University College London
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,052
Funders: United States Agency for International Development, International AIDS Vaccine Initiative, Wellcome Trust, National Research Foundation, Svenska Sällskapet för Medicinsk Forskning, Karolinska Institutet, Vetenskapsrådet, New Partnership for Africa's Development, Skånes universitetssjukhus, African Academy of Sciences, National Institutes of Health, Medical Research Council, Alliance for Accelerating Excellence in Science in Africa, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: VCT with Primary and Concurrent Partners to Prevent HIV Transmission , G1097787405, Family Planning Promotion in HIV Infected Zambians, The discriminatory ability of pre-treatment HIV-1 low frequency drug resistance variants to predict antiretroviral treatment outcomes, Characterization of hyperacute HIV infection in adults and infants to increase the understanding of HIV pathogenesis and opportunities for prevention, G2415674080, Design of HIV vaccines that stimulate T cell and NK cell immunity, G3000957577, G339059223, G4137015471, G4156438909, Pathogen Genomics, Phenotype and Immunity (PGPI) & Basic Sciences Programme, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE), G5901762629, G6199357630, CTL and HIV Polymorphisms in Heterosexual Transmission, G6277005470, G6590892262, The discriminatory ability of pre-treatment HIV-1 low frequency drug resistance variants to predict antiretroviral treatment outcomes, G6714156533, G6868616705, G704771751, Couples HIV Counseling & Testing in two African capitals, G7238354678, Virologic Correlates of Heterosexual Transmission, G8119020889, G8183321107, G8445079486, G8488937646, G8547154903, Emory National Primate Research Center, Deciphering the impact of sex in early subtype C HIV infection and during HART, Sub-Saharan African Network for TB/HIV research Excellence (SANTHE)
OpenAlex ID: W3127696471