Projects per year
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.
|Number of pages||13|
|Journal||Journal of Virology|
|Publication status||Published - 1 Aug 2017|
- Analytical treatment interruption
- HIV-1 cure
- Latencyreversing agent
- SMART trial
- 1 Curtailed
HIV latency, pathogenesis and immunity
Cooper, D. A., Davenport, M., Emery, S., Kelleher, A., Kent, S., Lewin, S. & Purcell, D. F. J.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 1/07/14