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

Hassan, Amin S LU ; Hare, Jonathan ; Gounder, Kamini ; Nazziwa, Jamirah LU orcid ; Karlson, Sara LU orcid ; Olsson, Linnéa ; Streatfield, Claire ; Kamali, Anatoli ; Karita, Etienne and Kilembe, William , et al. (2021) In Clinical Infectious Diseases 73(5). p.832-841
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Infectious Diseases
volume
73
issue
5
pages
832 - 841
publisher
Oxford University Press
external identifiers
  • pmid:33588436
  • scopus:85115907359
ISSN
1537-6591
DOI
10.1093/cid/ciab139
language
English
LU publication?
yes
id
65de6c48-e37e-4d7f-8cd7-73515ad0759a
date added to LUP
2021-02-23 15:28:07
date last changed
2024-04-18 03:09:07
@article{65de6c48-e37e-4d7f-8cd7-73515ad0759a,
  abstract     = {{<p>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.</p><p>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.</p><p>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 &gt;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).</p><p>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.</p>}},
  author       = {{Hassan, Amin S and Hare, Jonathan and Gounder, Kamini and Nazziwa, Jamirah and Karlson, Sara and Olsson, Linnéa and Streatfield, Claire and Kamali, Anatoli and Karita, Etienne and Kilembe, William and Price, Matt A and Borrow, Persephone and Björkman, Per and Kaleebu, Pontiano and Allen, Susan and Hunter, Eric and Ndung'u, Thumbi and Gilmour, Jill and Rowland-Jones, Sarah and Esbjörnsson, Joakim and Sanders, Eduard J}},
  issn         = {{1537-6591}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{5}},
  pages        = {{832--841}},
  publisher    = {{Oxford University Press}},
  series       = {{Clinical Infectious Diseases}},
  title        = {{A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome}},
  url          = {{http://dx.doi.org/10.1093/cid/ciab139}},
  doi          = {{10.1093/cid/ciab139}},
  volume       = {{73}},
  year         = {{2021}},
}