SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity

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 and J. Gerardo García-Lerma ()
Additional contact information
Michele B. Daly: Centers for Disease Control and Prevention
Chuong Dinh: Centers for Disease Control and Prevention
Angela Holder: Centers for Disease Control and Prevention
Donna Rudolph: Centers for Disease Control and Prevention
Susan Ruone: Centers for Disease Control and Prevention
Alison Swaims-Kohlmeier: Centers for Disease Control and Prevention
George Khalil: Centers for Disease Control and Prevention
Sunita Sharma: Centers for Disease Control and Prevention
James Mitchell: Centers for Disease Control and Prevention
Jillian Condrey: Centers for Disease Control and Prevention
Daniel Kim: Centers for Disease Control and Prevention
Yi Pan: Centers for Disease Control and Prevention
Kelly Curtis: Centers for Disease Control and Prevention
Peter Williams: Janssen Research & Development
William Spreen: ViiV Healthcare
Walid Heneine: Centers for Disease Control and Prevention
J. Gerardo García-Lerma: Centers for Disease Control and Prevention

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54783-0

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