SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity
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.
Authors
- Angela Holder (ORCID: https://orcid.org/0000-0002-4179-1297)
- Jose Gerardo Garcia-Lerma (ORCID: https://orcid.org/0000-0001-6437-7745)
- Susan Ruone (ORCID: https://orcid.org/0000-0002-0648-7038)
- George Khalil (ORCID: https://orcid.org/0000-0002-0996-0310)
- Walid Heneine (ORCID: https://orcid.org/0000-0003-3119-3565)
- William Spreen (ORCID: https://orcid.org/0000-0002-8180-1517)
- James H. Mitchell
- Yi Pan (ORCID: https://orcid.org/0000-0003-1978-475X)
- Jillian A. Condrey
- Michele B. Daly
- Kelly A. Curtis (ORCID: https://orcid.org/0000-0002-1785-6548)
- D.H. Kim (ORCID: https://orcid.org/0009-0001-7279-882X)
- Peter Williams (ORCID: https://orcid.org/0000-0001-8118-0602)
- Sunita Sharma
- Alison Swaims-Kohlmeier (ORCID: https://orcid.org/0000-0001-6508-0038)
- Donna L. Rudolph
- Chuong Dinh
Institutions
- Centers for Disease Control and Prevention (US)
- Janssen (Belgium) (BE)
- Emory University (US)
- Triangle (US)
- Centers for Disease Control and Prevention (UG)
- National Center for HIV/AIDS Viral Hepatitis STD and TB Prevention (US)
- National Center for Emerging and Zoonotic Infectious Diseases (US)
- The Centers (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-04
- DOI
- https://doi.org/10.1038/s41467-024-54783-0
- Citations
- 2
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.59
Funders
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute of Allergy and Infectious Diseases