Join the fight to achieve global malaria elimination targets
Donate today and join the fight to achieve global malaria elimination targets.
Together we can make a significant contribution to achieving malaria elimination targets.
Donate today and join the fight to achieve global malaria elimination targets.
Together we can make a significant contribution to achieving malaria elimination targets.
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 (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We find that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI) of 21-59 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 of 2 to 12 months amongst 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 there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies towards eliminating latently infected cells.
IMPORTANCE The “shock and kill” HIV-1 cure strategy aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. Several latency reversing agents (LRA) have been examined in vivo, but LRAs alone have not been able to achieve HIV-1 remission and prevent viral rebound following analytical treatment interruption (ATI). Here, we examine whether LRA treatment or ATI can provide sufficient antigenic stimulus to boost HIV-1-specific functional antibodies that can eliminate HIV-1-infected cells. Our study has implications for the antigenic stimulus required for anti-latency strategies and/or therapeutic vaccines to boost functional antibodies and assist in eliminating the latent reservoir.