Administration of the BCL-2 antagonist, venetoclax, to promote apoptosis of HIV-infected cells and reduce the size of the HIV reservoir: An investigator-initiated phase I/IIb clinical trial in people living with HIV on antiretroviral therapy. The AMBER Study. (NCT05668026)

AMBER is a clinical trial to investigate if venetoclax, a medication which promotes cell death (apoptosis), can promote cell death of long-lived HIV infected cells and lead to a reduction of the latent HIV reservoir. The first part in Denmark used different doses of venetoclax to establish the safest dose to use in people with HIV. The second part of the study is taking place both in Aarhus, Denmark and here in Melbourne, Australia. All participants in part 2 of the study will stay on their ART and receive 3 cycles of the optimal dose of venetoclax determined in the first part of the trial. These cycles are 28 days consisting of 14 days on treatment and 14 days off treatment.  The main outcome of the study is to determine the safety of venetoclax in people with HIV and then blood samples will be collected to understand if veneotclax has an effect on the size of the HIV reservoir and whether the drug is leading to the loss of HIV-infected cells.

Trial phase

Phase 2

Trial participation type

This trial has been designed for the Clinical Research of a Drug.

Principal investigator

Prof James McMahon

Key inclusion data

Key inclusion: Documented HIV-1 infection Age 18-70 years, both included Receiving combination ART for at least 2 years HIV-1 plasma RNA <50 copies/mL for >2 years CD4+ T cell count >500 cells/yL at screening Key exclusion: Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy Any concomitant disease where venetoclax treatment is indicated Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin) Current use of any HIV protease inhibitor (due to CYP3A4 inhibition) Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin) Current use of strong CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin and St. John's wort)