Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen
There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boo...
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| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/16/2/182 |
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| author | Arjen J. Stam Ninée V. E. J. Buchholtz Wouter F. W. Bierman Reinout van Crevel Andy I. M. Hoepelman Mark A. A. Claassen Heidi S. M. Ammerlaan Berend J. van Welzen Marjo E. E. van Kasteren Steven F. L. van Lelyveld Dorien de Jong Kiki Tesselaar Matthijs van Luin Monique Nijhuis Annemarie M. J. Wensing LOWERIT Study Team |
| author_facet | Arjen J. Stam Ninée V. E. J. Buchholtz Wouter F. W. Bierman Reinout van Crevel Andy I. M. Hoepelman Mark A. A. Claassen Heidi S. M. Ammerlaan Berend J. van Welzen Marjo E. E. van Kasteren Steven F. L. van Lelyveld Dorien de Jong Kiki Tesselaar Matthijs van Luin Monique Nijhuis Annemarie M. J. Wensing LOWERIT Study Team |
| author_sort | Arjen J. Stam |
| collection | DOAJ |
| description | There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV. |
| first_indexed | 2024-03-07T22:11:35Z |
| format | Article |
| id | doaj.art-f26c5e2ea53642dd922ae0760c7e8299 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-07T22:11:35Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f26c5e2ea53642dd922ae0760c7e82992024-02-23T15:37:25ZengMDPI AGViruses1999-49152024-01-0116218210.3390/v16020182Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based RegimenArjen J. Stam0Ninée V. E. J. Buchholtz1Wouter F. W. Bierman2Reinout van Crevel3Andy I. M. Hoepelman4Mark A. A. Claassen5Heidi S. M. Ammerlaan6Berend J. van Welzen7Marjo E. E. van Kasteren8Steven F. L. van Lelyveld9Dorien de Jong10Kiki Tesselaar11Matthijs van Luin12Monique Nijhuis13Annemarie M. J. Wensing14LOWERIT Study TeamTranslational Virology Research Group, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology Research Group, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Internal Medicine, Rijnstate Hospital, 6815 AD Arnhem, The NetherlandsDepartment of Internal Medicine, Catharina Hospital, 5623 EJ Eindhoven, The NetherlandsDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Internal Medicine, ETZ Hospital, 5022 GC Tilburg, The NetherlandsDepartment of Internal Medicine, Spaarne Gasthuis, 2000 TM Hoofddorp, The NetherlandsTranslational Virology Research Group, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Clinical Pharmacy, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology Research Group, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsTranslational Virology Research Group, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsThere is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV.https://www.mdpi.com/1999-4915/16/2/182HIV-1low-level viremiaimmune activationHIV pathogenesisreplicationproduction |
| spellingShingle | Arjen J. Stam Ninée V. E. J. Buchholtz Wouter F. W. Bierman Reinout van Crevel Andy I. M. Hoepelman Mark A. A. Claassen Heidi S. M. Ammerlaan Berend J. van Welzen Marjo E. E. van Kasteren Steven F. L. van Lelyveld Dorien de Jong Kiki Tesselaar Matthijs van Luin Monique Nijhuis Annemarie M. J. Wensing LOWERIT Study Team Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen Viruses HIV-1 low-level viremia immune activation HIV pathogenesis replication production |
| title | Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen |
| title_full | Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen |
| title_fullStr | Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen |
| title_full_unstemmed | Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen |
| title_short | Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen |
| title_sort | dynamics of low level viremia and immune activation after switching to a darunavir based regimen |
| topic | HIV-1 low-level viremia immune activation HIV pathogenesis replication production |
| url | https://www.mdpi.com/1999-4915/16/2/182 |
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