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 Esbjörnsson; Eduard J Sanders

doi:10.1093/cid/ciab139

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 journal › Article › peer-review

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 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 language	English
Pages (from-to)	832-841
Journal	Clinical Infectious Diseases
Volume	73
Issue number	5
Early online date	2021 Feb 15
DOIs	https://doi.org/10.1093/cid/ciab139
Publication status	Published - 2021

Subject classification (UKÄ)

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

Access to Document

10.1093/cid/ciab139Licence: CC BY-NC-ND

1 Doctoral Thesis (compilation)

Dynamics of HIV-1 infection within and between hosts
Nazziwa, J., 2022, Lund: Lund University, Faculty of Medicine. 104 p.
Research output: Thesis › Doctoral Thesis (compilation)

Open Access
File

Cite this

Hassan, A. S., Hare, J., Gounder, K., Nazziwa, J., Karlson, S., Olsson, L., Streatfield, C., Kamali, A., Karita, E., Kilembe, W., Price, M. A., Borrow, P., Björkman, P., Kaleebu, P., Allen, S., Hunter, E., Ndung'u, T., Gilmour, J., Rowland-Jones, S., ... Sanders, E. J. (2021). A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome. Clinical Infectious Diseases, 73(5), 832-841. https://doi.org/10.1093/cid/ciab139

@article{65de6c48e37e4d7f8cd773515ad0759a,

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

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 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.",

author = "Hassan, {Amin S} and Jonathan Hare and Kamini Gounder and Jamirah Nazziwa and Sara Karlson and Linn{\'e}a Olsson and Claire Streatfield and Anatoli Kamali and Etienne Karita and William Kilembe and Price, {Matt A} and Persephone Borrow and Per Bj{\"o}rkman and Pontiano Kaleebu and Susan Allen and Eric Hunter and Thumbi Ndung'u and Jill Gilmour and Sarah Rowland-Jones and Joakim Esbj{\"o}rnsson and Sanders, {Eduard J}",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.",

year = "2021",

doi = "10.1093/cid/ciab139",

language = "English",

volume = "73",

pages = "832--841",

journal = "Clinical Infectious Diseases",

issn = "1537-6591",

publisher = "Oxford University Press",

number = "5",

}

Hassan, AS, Hare, J, Gounder, K, Nazziwa, J , Karlson, S, Olsson, L, Streatfield, C, Kamali, A, Karita, E, Kilembe, W, Price, MA, Borrow, P, Björkman, P, Kaleebu, P, Allen, S, Hunter, E, Ndung'u, T, Gilmour, J, Rowland-Jones, S, Esbjörnsson, J & Sanders, EJ 2021, 'A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome', Clinical Infectious Diseases, vol. 73, no. 5, pp. 832-841. https://doi.org/10.1093/cid/ciab139

TY - JOUR

T1 - A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome

AU - Hassan, Amin S

AU - Hare, Jonathan

AU - Gounder, Kamini

AU - Nazziwa, Jamirah

AU - Karlson, Sara

AU - Olsson, Linnéa

AU - Streatfield, Claire

AU - Kamali, Anatoli

AU - Karita, Etienne

AU - Kilembe, William

AU - Price, Matt A

AU - Borrow, Persephone

AU - Björkman, Per

AU - Kaleebu, Pontiano

AU - Allen, Susan

AU - Hunter, Eric

AU - Ndung'u, Thumbi

AU - Gilmour, Jill

AU - Rowland-Jones, Sarah

AU - Esbjörnsson, Joakim

AU - Sanders, Eduard J

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1093/cid/ciab139

DO - 10.1093/cid/ciab139

M3 - Article

C2 - 33588436

VL - 73

SP - 832

EP - 841

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1537-6591

IS - 5

ER -

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

Abstract

Subject classification (UKÄ)

Access to Document

Fingerprint

Research output

Dynamics of HIV-1 infection within and between hosts

Cite this