Tracking HIV Rebound following Latency Reversal Using Barcoded HIV
Matthew D. Marsden, Tianhao Zhang, Yushen Du, Melanie Dimapasoc, Mohamed S. Soliman, Xiaomeng Wu, Jocelyn T. Kim, Akira Shimizu, Adam J. Schrier, Paul A. Wender, Ren Sun, Jerome A. Zack
Abstract
HIV latency prevents cure of infection with antiretroviral therapy (ART) alone. One strategy for eliminating latently infected cells involves the induction of viral protein expression via latency-reversing agents (LRAs), allowing killing of host cells by viral cytopathic effects or immune effector mechanisms. Here, we combine a barcoded HIV approach and a humanized mouse model to study the effects of a designed, synthetic protein kinase C modulating LRA on HIV rebound. We show that administration of this compound during ART results in a delay in rebound once ART is stopped. Furthermore, the rebounding virus appears composed of a smaller number of unique barcoded viruses than occurs in control-treated animals, suggesting that some reservoir cells that would have contributed virus to the rebound process are eliminated by LRA administration. These data support the use of barcoded virus to study rebound and suggest that LRAs may be useful in HIV cure efforts.