SMAC Mimetic Plus Triple-Combination Bispecific HIVxCD3 Retargeting Molecules in SHIV.C.CH505-Infected, Antiretroviral Therapy-Suppressed Rhesus Macaques
Amir Dashti, Chevaughn Waller, Maud Mavigner, Nils Schoof, Katharine J. Bar, George M. Shaw, Thomas H. Vanderford, Shan Liang, Jeffrey D. Lifson, Richard M. Dunham, Guido Ferrari, Marina Tuyishime, Chia‐Ying K. Lam, Jeffrey L. Nordstrom, David M. Margolis, Guido Silvestri, Ann Chahroudi
Abstract
The most significant barrier to an HIV-1 cure is the existence of the latently infected viral reservoir that gives rise to rebound viremia upon cessation of ART. Here, we tested a novel combination approach of latency reversal with AZD5582 and clearance with bispecific HIVxCD3 DART molecules in SHIV.C.CH505-infected, ART-suppressed rhesus macaques. We demonstrate that the DART molecules were not capable of clearing infected cells in vivo , attributed to the lack of quantifiable latency reversal in this model with low levels of persistent SHIV DNA prior to intervention as well as DART molecule immunogenicity.