A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome

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 EsbjörnssonEduard J Sanders

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Acute retroviral syndrome (ARS) is associated with 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 analysed. 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 eleven 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% CI: 1.7-28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven 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.

Original languageEnglish
Pages (from-to)832-841
JournalClinical Infectious Diseases
Issue number5
Early online date2021 Feb 15
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Microbiology in the medical area
  • Immunology in the medical area
  • Infectious Medicine


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