Publications & Reports

Anti-HIV-1 ADCC antibodies following latency reversal and treatment interruption.

Lee WS, Kristensen AB, Rasmussen TA, Tolstrup M, Østergaard L, Søgaard OS, Wines BD, Hogarth PM, Reynaldi A, Davenport MP, Emery S, Amin J, Cooper DA, Kan VL, Fox J, Gruell H, Parsons MS, Kent SJ

Abstract

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.

Link to publisher’s web site

Publication

  • Journal: Journal of Virology
  • Published: 01/08/2017
  • Volume: 91
  • Issue: 15
  • Pagination: e00603

Authors