SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity
Abstract Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advant...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54783-0 |
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| author | Michele B. Daly Chuong Dinh Angela Holder Donna Rudolph Susan Ruone Alison Swaims-Kohlmeier George Khalil Sunita Sharma James Mitchell Jillian Condrey Daniel Kim Yi Pan Kelly Curtis Peter Williams William Spreen Walid Heneine J. Gerardo García-Lerma |
| author_facet | Michele B. Daly Chuong Dinh Angela Holder Donna Rudolph Susan Ruone Alison Swaims-Kohlmeier George Khalil Sunita Sharma James Mitchell Jillian Condrey Daniel Kim Yi Pan Kelly Curtis Peter Williams William Spreen Walid Heneine J. Gerardo García-Lerma |
| author_sort | Michele B. Daly |
| collection | DOAJ |
| description | Abstract Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia. We document full suppression in all animals during treatment (4-12 months) and no virus rebound after treatment discontinuation (1.5-2 years of follow up) despite CD8 + T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation. |
| format | Article |
| id | doaj-art-4f90d82ee7bb4dc8b7f56f9adf3b9032 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4f90d82ee7bb4dc8b7f56f9adf3b90322025-08-20T02:30:56ZengNature PortfolioNature Communications2041-17232024-12-0115111210.1038/s41467-024-54783-0SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activityMichele B. Daly0Chuong Dinh1Angela Holder2Donna Rudolph3Susan Ruone4Alison Swaims-Kohlmeier5George Khalil6Sunita Sharma7James Mitchell8Jillian Condrey9Daniel Kim10Yi Pan11Kelly Curtis12Peter Williams13William Spreen14Walid Heneine15J. Gerardo García-Lerma16Laboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionQuantitative Sciences and Data Management Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionComparative Medicine Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionQuantitative Sciences and Data Management Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionJanssen Research & DevelopmentViiV HealthcareLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionLaboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and PreventionAbstract Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia. We document full suppression in all animals during treatment (4-12 months) and no virus rebound after treatment discontinuation (1.5-2 years of follow up) despite CD8 + T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation.https://doi.org/10.1038/s41467-024-54783-0 |
| spellingShingle | Michele B. Daly Chuong Dinh Angela Holder Donna Rudolph Susan Ruone Alison Swaims-Kohlmeier George Khalil Sunita Sharma James Mitchell Jillian Condrey Daniel Kim Yi Pan Kelly Curtis Peter Williams William Spreen Walid Heneine J. Gerardo García-Lerma SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity Nature Communications |
| title | SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity |
| title_full | SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity |
| title_fullStr | SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity |
| title_full_unstemmed | SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity |
| title_short | SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity |
| title_sort | shiv remission in macaques with early treatment initiation and ultra long lasting antiviral activity |
| url | https://doi.org/10.1038/s41467-024-54783-0 |
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