Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption
Journal of Virology
ADCC; Analytical treatment interruption; HIV-1 cure; Latency; Latencyreversing agent; Panobinostat; SMART trial
© 2017 American Society for Microbiology. There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells.
Lee, W., Kristensen, A., Rasmussen, T., Tolstrup, M., Østergaard, L., Søgaard, O., Wines, B., Mark Hogarth, P., Reynaldi, A., Davenport, M., Emery, S., Amin, J., Cooper, D., Kan, V., Fox, J., Gruell, H., Parsons, M., & Kent, S. (2017). Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption. Journal of Virology, 91 (15). http://dx.doi.org/10.1128/JVI.00603-17