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
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 N...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.878743/full |
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| author | Matthew Pace Ane Ogbe Jacob Hurst Nicola Robinson Jodi Meyerowitz Natalia Olejniczak John P. Thornhill John P. Thornhill Mathew Jones Anele Waters Julianne Lwanga Kristen Kuldanek Rebecca Hall Panagiota Zacharopoulou Genevieve E. Martin Genevieve E. Martin Helen Brown Nneka Nwokolo Dimitra Peppa Julie Fox Sarah Fidler Sarah Fidler Sarah Fidler John Frater John Frater |
| author_facet | Matthew Pace Ane Ogbe Jacob Hurst Nicola Robinson Jodi Meyerowitz Natalia Olejniczak John P. Thornhill John P. Thornhill Mathew Jones Anele Waters Julianne Lwanga Kristen Kuldanek Rebecca Hall Panagiota Zacharopoulou Genevieve E. Martin Genevieve E. Martin Helen Brown Nneka Nwokolo Dimitra Peppa Julie Fox Sarah Fidler Sarah Fidler Sarah Fidler John Frater John Frater |
| author_sort | Matthew Pace |
| collection | DOAJ |
| description | 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 CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright 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 CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg 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. |
| first_indexed | 2024-12-10T18:01:40Z |
| format | Article |
| id | doaj.art-c26713386e8c4f139f8aa0249aaa10a7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T18:01:40Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c26713386e8c4f139f8aa0249aaa10a72022-12-22T01:38:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.878743878743Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruptionMatthew Pace0Ane Ogbe1Jacob Hurst2Nicola Robinson3Jodi Meyerowitz4Natalia Olejniczak5John P. Thornhill6John P. Thornhill7Mathew Jones8Anele Waters9Julianne Lwanga10Kristen Kuldanek11Rebecca Hall12Panagiota Zacharopoulou13Genevieve E. Martin14Genevieve E. Martin15Helen Brown16Nneka Nwokolo17Dimitra Peppa18Julie Fox19Sarah Fidler20Sarah Fidler21Sarah Fidler22John Frater23John Frater24Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomEtcembly Ltd, Harwell Campus, Didcot, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Infection, Guys and St Thomas’ National Health Service (NHS) Trust, London, United KingdomDepartment of Infection, Guys and St Thomas’ National Health Service (NHS) Trust, London, United KingdomDepartment of HIV Medicine, St Mary’s Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomDepartment of HIV Medicine, St Mary’s Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of Infectious Diseases, Monash University, Melbourne, VIC, AustraliaNuffield Department of Medicine, University of Oxford, Oxford, United KingdomDepartment of HIV/GUM, Chelsea and Westminster Hospital, London, United KingdomDivision of Infection and Immunity, University College, London, United KingdomDepartment of Infection, Guys and St Thomas’ National Health Service (NHS) Trust, London, United KingdomDepartment of HIV Medicine, St Mary’s Hospital, Imperial College Healthcare National Health Service (NHS) Trust, London, United KingdomDepartment of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom0National Institute for Health and Care Research (NIHR) Imperial College Biomedical Research Centre, London, United KingdomNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom1National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, Oxford, United KingdomNatural 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 CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright 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 CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.878743/fullHIV-human immunodeficiency virusNK cellviral reboundantiretroviral (ARV)treatment interruption (TI) |
| spellingShingle | Matthew Pace Ane Ogbe Jacob Hurst Nicola Robinson Jodi Meyerowitz Natalia Olejniczak John P. Thornhill John P. Thornhill Mathew Jones Anele Waters Julianne Lwanga Kristen Kuldanek Rebecca Hall Panagiota Zacharopoulou Genevieve E. Martin Genevieve E. Martin Helen Brown Nneka Nwokolo Dimitra Peppa Julie Fox Sarah Fidler Sarah Fidler Sarah Fidler John Frater John Frater 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 Frontiers in Immunology HIV-human immunodeficiency virus NK cell viral rebound antiretroviral (ARV) treatment interruption (TI) |
| 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 interruption |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | HIV-human immunodeficiency virus NK cell viral rebound antiretroviral (ARV) treatment interruption (TI) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.878743/full |
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