Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruption Article Swipe
Matthew Pace
,
Ane Ogbe
,
Jacob Hurst
,
Nicola Robinson
,
Jodi Meyerowitz
,
Natalia Olejniczak
,
John Thornhill
,
Mathew Jones
,
Anele Waters
,
Julianne Lwanga
,
Kristen Kuldanek
,
Rebecca Hall
,
Panagiota Zacharopoulou
,
Geneviève Martin
,
Helen Brown
,
Nneka Nwokolo
,
Dimitra Peppa
,
Julie Fox
,
Sarah Fidler
,
John Frater
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.878743
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.878743
Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56 dim NK cells, Tim-3 expression in CD56 bright NK cells, IFN-γ expressed by CD56 dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56 dim and CD56 bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56 dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56 neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound.
Related Topics
Concepts
Antiretroviral therapy
Virology
Human immunodeficiency virus (HIV)
Medicine
Viral load
Immunology
Lentivirus
Antiretroviral treatment
Biology
Viral disease
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2022.878743
- OA Status
- gold
- Cited By
- 7
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4293694672
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4293694672Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2022.878743Digital Object Identifier
- Title
-
Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruptionWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-08-30Full publication date if available
- Authors
-
Matthew Pace, Ane Ogbe, Jacob Hurst, Nicola Robinson, Jodi Meyerowitz, Natalia Olejniczak, John Thornhill, Mathew Jones, Anele Waters, Julianne Lwanga, Kristen Kuldanek, Rebecca Hall, Panagiota Zacharopoulou, Geneviève Martin, Helen Brown, Nneka Nwokolo, Dimitra Peppa, Julie Fox, Sarah Fidler, John FraterList of authors in order
- Landing page
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https://doi.org/10.3389/fimmu.2022.878743Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.3389/fimmu.2022.878743Direct OA link when available
- Concepts
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Antiretroviral therapy, Virology, Human immunodeficiency virus (HIV), Medicine, Viral load, Immunology, Lentivirus, Antiretroviral treatment, Biology, Viral diseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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7Total citation count in OpenAlex
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2025: 2, 2024: 4, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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48Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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