Broadly neutralizing antibodies combined with latency-reversing agents or immune modulators as strategy for HIV-1 remission.

Abstract

Antiretroviral therapy (ART) is extremely effective in controlling HIV-1 infection; however, ART is not curative. Here, we review broadly neutralizing anti-HIV-1 antibodies (bNAbs) combined with latency-reversing agents (LRAs) or immune modulators as strategy for achieving long-term HIV-1 remission. Clinical trials testing the effect of a single intervention such as a LRA 'shock and kill', immune modulator or bNAbs among HIV-1 infected individuals on long-term suppressive ART have not lead to long-term HIV-1 remission when ART is stopped. Novel combinations of interventions designed to eliminate infected cells and enhance immune-effector functions are being investigated. Findings in nonhuman primates (NHPs) of such combinations are very promising and clinical trials are now ongoing. These trials will provide the first indication of the efficacy of combinations of bNAbs and LRA or immune modulators for achieving durable HIV-1 remission. bNAbs facilitate the elimination of HIV-1 infected cells and boost immune responses. Preclinical findings show that these effects can be harnessed by simultaneous administration of LRAs or immune modulators such as Toll-like receptor agonists. The clinical success of such combination strategies may be impacted by factors such as immune exhaustion, bNAbs sensitivity as well as the pharmacodynamics of the investigational compounds.