Virological and immunological correlates of HIV posttreatment control after temporal antiretroviral therapy during acute HIV infection
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc..
OBJECTIVE: People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary posttreatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC.
DESIGN/METHODS: Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay, and quantitative viral outgrowth assay. Viral replication kinetics were determined in autologous and donor PBMC. IgG levels directed against HIV envelope and neutralizing antibodies were measured. Immune phenotyping of T cells and HIV-specific T-cell responses were analyzed by flow cytometry.
RESULTS: The case presented with AHI and a plasma viral load of 2.7 million copies/ml. ART was initiated 2 weeks after diagnosis and interrupted after 26 months. Replicating virus was isolated shortly after start ART. At 18 years after treatment interruption, HIV-DNA in CD4 + T cells and low levels of HIV-RNA in plasma (<5 copies/ml) were detectable. Stable HIV envelope glycoprotein-directed IgG was present during follow-up, but lacked neutralizing activity. Strong antiviral CD8 + T-cell responses, in particular targeting HIV-gag, were detected during 25 years follow-up. Moreover, we found a P255A mutation in an HLA-B∗44 : 02 restricted gag-epitope, which was associated with decreased replication.
CONCLUSION: We describe an exceptional case of PTC, which is likely associated with sustained potent gag-specific CD8 + T-cell responses in combination with a replication attenuating escape mutation in gag. Understanding the initiation and preservation of the HIV-specific T-cell responses could guide the development of strategies to induce HIV control.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
AIDS (London, England) - 37(2023), 15 vom: 01. Dez., Seite 2297-2304 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van Paassen, Pien M [VerfasserIn] |
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| Links: |
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| Themen: |
9007-49-2 |
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| Anmerkungen: |
Date Completed 16.11.2023 Date Revised 07.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1097/QAD.0000000000003722 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361997493 |
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| 100 | 1 | |a van Paassen, Pien M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Virological and immunological correlates of HIV posttreatment control after temporal antiretroviral therapy during acute HIV infection |
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| 500 | |a Date Completed 16.11.2023 | ||
| 500 | |a Date Revised 07.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. | ||
| 520 | |a OBJECTIVE: People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary posttreatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC | ||
| 520 | |a DESIGN/METHODS: Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay, and quantitative viral outgrowth assay. Viral replication kinetics were determined in autologous and donor PBMC. IgG levels directed against HIV envelope and neutralizing antibodies were measured. Immune phenotyping of T cells and HIV-specific T-cell responses were analyzed by flow cytometry | ||
| 520 | |a RESULTS: The case presented with AHI and a plasma viral load of 2.7 million copies/ml. ART was initiated 2 weeks after diagnosis and interrupted after 26 months. Replicating virus was isolated shortly after start ART. At 18 years after treatment interruption, HIV-DNA in CD4 + T cells and low levels of HIV-RNA in plasma (<5 copies/ml) were detectable. Stable HIV envelope glycoprotein-directed IgG was present during follow-up, but lacked neutralizing activity. Strong antiviral CD8 + T-cell responses, in particular targeting HIV-gag, were detected during 25 years follow-up. Moreover, we found a P255A mutation in an HLA-B∗44 : 02 restricted gag-epitope, which was associated with decreased replication | ||
| 520 | |a CONCLUSION: We describe an exceptional case of PTC, which is likely associated with sustained potent gag-specific CD8 + T-cell responses in combination with a replication attenuating escape mutation in gag. Understanding the initiation and preservation of the HIV-specific T-cell responses could guide the development of strategies to induce HIV control | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a van Pul, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a van der Straten, Karlijn |e verfasserin |4 aut | |
| 700 | 1 | |a Buchholtz, Ninée V J E |e verfasserin |4 aut | |
| 700 | 1 | |a Grobben, Marloes |e verfasserin |4 aut | |
| 700 | 1 | |a van Nuenen, Ad C |e verfasserin |4 aut | |
| 700 | 1 | |a van Dort, Karel A |e verfasserin |4 aut | |
| 700 | 1 | |a Boeser-Nunnink, Brigitte D |e verfasserin |4 aut | |
| 700 | 1 | |a van den Essenburg, Mo D |e verfasserin |4 aut | |
| 700 | 1 | |a Burger, Judith A |e verfasserin |4 aut | |
| 700 | 1 | |a van Luin, Matthijs |e verfasserin |4 aut | |
| 700 | 1 | |a Jurriaans, Suzanne |e verfasserin |4 aut | |
| 700 | 1 | |a Sanders, Rogier W |e verfasserin |4 aut | |
| 700 | 1 | |a Swelsen, Wendy T |e verfasserin |4 aut | |
| 700 | 1 | |a Symons, Jori |e verfasserin |4 aut | |
| 700 | 1 | |a Klouwens, Michelle J |e verfasserin |4 aut | |
| 700 | 1 | |a Nijhuis, Monique |e verfasserin |4 aut | |
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| 700 | 1 | |a Prins, Jan M |e verfasserin |4 aut | |
| 700 | 1 | |a de Bree, Godelieve J |e verfasserin |4 aut | |
| 700 | 1 | |a Kootstra, Neeltje A |e verfasserin |4 aut | |
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