Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT06282783 |
Other study ID # |
2024-511532-27-00 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 1/Phase 2
|
First received |
|
Last updated |
|
Start date |
September 2024 |
Est. completion date |
August 2025 |
Study information
Verified date |
February 2024 |
Source |
Erasmus Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Even with current HIV treatments, HIV is still a lifelong disease because it hides in some
long-lasting cells in the body. One of the strategies to find a cure for HIV works by finding
the virus in these cells, making it visible, and then getting rid of it. This is called the
'shock and kill' approach.
So far, the drugs tested can find the virus, but they don't get rid of it completely. That's
why there need to be new drugs that can do this more effectively. The Erasmus MC HIV
Eradication Group (EHEG) has been testing new drugs in the lab and found a drug called
topiramate can wake up the virus without harming the cells. The aim of this study is to test
topiramate in people living with HIV.
Most of the people that participate in HIV cure studies are men, even though most people
living with HIV around the world are women. Previous research has shown that men and women
might respond differently to these treatments. So, in this study, topiramate will be
investigated in both men and women. This could help us find a cure that works for everyone.
Description:
Despite antiretroviral therapy (ART), an infection with the human immunodeficiency virus 1
(HIV-1) is still a lifelong disease because of the latent HIV reservoir. This reservoir
consists of a pool of long-lived cells harbouring an integrated copy of the HIV provirus in
its genome. One approach to curing HIV centres on reversing viral latency, combined with the
subsequent elimination of the virus from this reservoir specifically, all while safeguarding
other cells through the use of ART. This approach is colloquially known as 'shock and kill'.
The limited number of latency reversing agents (LRAs) that have been studied were effective
at reactivating the latent reservoir, but do not result in significant reservoir reduction
(Debrabander, 2023). Investigating novel LRAs is, therefore, necessary to identify more
potent ways of HIV reactivation, with the ultimate goal of reservoir depletion i.e. a
functional HIV cure. The Erasmus MC HIV Eradication group has set up a translational trial
platform, where successfully study the effects of novel LRAs from bench to bedside. One
example is the discovery of small molecule inhibitors of BAF, which reverse HIV-1 latency, to
a clinical trial investigating pyrimethamine in people living with HIV (PLWH) (Stoszko, 2016;
Prins, 2023). A new promising drug target that was identified in EHEG is the glutamate
receptor, ionotropic kainate 5 (GRIK5); a host factor involved in HIV latency (Roling, 2021).
The registered drug topiramate was identified as a potential GRIK5 inhibitor. Further ex vivo
testing confirmed HIV latency reversal of topiramate at therapeutic levels without inducing
cytotoxic effects. This opens new opportunities for HIV cure research. A further knowledge
gap to be explored is the influence of sex in HIV latency reversal. Typically, either by
design or recruitment, male participants have been vastly overrepresented in HIV cure
research (Barr, 2020). This is despite previous research showing significant difference in
HIV latency reversal in women (Rao, 2022), and the importance of sex in pharmacodynamics
being increasingly recognised (Gandhi, 2004; Mauvais-Jarvis, 2021). As the majority of PLWH
worldwide are women and their numbers are expected to grow, studies on any potential cure
strategy that provide an evidence base for their use in women increase clinical impact
(UNAIDS, 2023). Therefore, the aim of this study is to examine the effect and safety of
topiramate as an LRA in both men and women.