Early administration of anti-latency reversing therapy and broadly neutralizing antibodies to limit the establishment of the HIV-1 reservoir during initiation of antiretroviral treatment - a randomized controlled trial (eCLEAR)
Department of Infectious Diseases, Aarhus University Hospital
Duration of Study in the UK
2 years, 0 months, 1 days
Despite effective highly active antiretroviral therapy (ART), HIV persists as a latent infection. ART works by stopping HIV replicating. Upon treatment interruption, the virus quickly replicates and virus levels in blood rebounds to pre-treatment levels.
The primary barrier preventing eradication of HIV-infection by ART is a pool of long-lived latently infected memory immune cells. In the inactive, resting state, HIV-infected cells (HIV reservoir) are unrecognisable to the immune system and unresponsive to antiretroviral drugs. One proposed strategy to eliminate the HIV-1 reservoir is the ‘kick-and-kill’ strategy where the reservoir is exposed to the immune system (kick), and subsequently infected cells are 'killed' through immunotherapy using potent broadly neutralizing antibodies. Viral reactivation can be achieved by using a class of small molecule drugs called histone deacetylase inhibitors that act as latency reversing agents (LRA) and reactivate the virus (kick) in cells, presenting the HIV reservoir to the immune system.
This study will combine the use of 3BNC117, a potent broadly neutralizing antibody, with a potent latency reversing agent, romidepsin, as a novel approach to reduce the HIV-1 reservoir in ART naïve patients initiating ART.
The study is a phase IIa multicenter non-blinded randomized controlled trial with eligible participants (n=60, 15 patients per arm) randomized 1:1:1:1 to one of four regimens:
A. ART alone
B. ART + romidepsin,
C. ART + 3BNC117
D. ART + romidepsin + 3BNC117.
Subjects will continue background ART while receiving the remaining course of romidepsin and/or 3BNC117.
The study aims to evaluate the effect of early viral reactivation and/or administration of potent broadly neutralizing antibodies on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating ART; and to evaluate the safety and tolerability of the Investigational Medicinal Products.
London - West London & GTAC Research Ethics Committee
Date of REC Opinion
11 Jun 2018
Further Information Favourable Opinion