A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome
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 Pla...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2021
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| _version_ | 1826262579226345472 |
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| author | Hassan, AS Hare, J Gounder, K Borrow, P Rowland-Jones, S Esbjörnsson, J Sanders, E Et al. |
| author_facet | Hassan, AS Hare, J Gounder, K Borrow, P Rowland-Jones, S Esbjörnsson, J Sanders, E Et al. |
| author_sort | Hassan, AS |
| collection | OXFORD |
| description | 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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| first_indexed | 2024-03-06T19:38:26Z |
| format | Journal article |
| id | oxford-uuid:1fd506fb-75cb-4e6f-98c9-776776cf9515 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:38:26Z |
| publishDate | 2021 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:1fd506fb-75cb-4e6f-98c9-776776cf95152022-03-26T11:24:18ZA stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndromeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1fd506fb-75cb-4e6f-98c9-776776cf9515EnglishSymplectic ElementsOxford University Press2021Hassan, ASHare, JGounder, KBorrow, PRowland-Jones, SEsbjörnsson, JSanders, EEt al.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. |
| spellingShingle | Hassan, AS Hare, J Gounder, K Borrow, P Rowland-Jones, S Esbjörnsson, J Sanders, E Et al. A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome |
| title | A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome |
| title_full | A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome |
| title_fullStr | A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome |
| title_full_unstemmed | A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome |
| title_short | A stronger innate immune response during hyperacute HIV-1 infection is associated with acute retroviral syndrome |
| title_sort | stronger innate immune response during hyperacute hiv 1 infection is associated with acute retroviral syndrome |
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