15 Dec Anti–HIV Drug Candidate Prevents Intestinal Inflammation
MedicalResearch.com Interview with:
Prof. Jamal Tazi
Director, Institute for Molecular Genetics
CNRS and University of Montpellier and Executive Committee Member
MedicalResearch.com: What is the background for this study?
Response: Its long been established that people with HIV, even those treated successfully with antiretroviral treatment, exhibit significantly higher levels of chronic inflammation than HIV-negative people. The causes of this inflammation are many – ongoing viral replication, often in the so-called viral reservoirs, leaky gut syndrome, concomitant viral infections (eg CMV, hepatitis etc).
MedicalResearch.com: What are the main findings?
Response: The data presented at the DART conference show that in in vitro models, ABX464 exposure leads to a 50-fold upregulation of IL-22, a potent anti-inflammatory cytokine, by macrophages as well as a 10-fold upregulation of the anti-inflammatory microRNA miR-124 in T-lymphocytes. In addition, in a preclinical model of colitis, treatment with ABX464 reduces macrophage recruitment into the intestine and also inflammatory cytokine release (IL-6 and TNFa), thereby preventing the histological changes of the gut associated with colitis.
Furthermore, after stopping treatment, the protective effect of ABX464 in this disease model lasted for at least 6 weeks despite continued exposure to DSS, a substance well known to induce the pathological features of colitis. This therapeutic effect is mediated at least in part by IL-22, an anti-inflammatory cytokine known to regulate tissue repair and recovery from colon injury, as antibodies to IL-22 partly abolished this protection.
MedicalResearch.com: What should readers take away from your report?
Response: Our studies suggest that ABX464 may be able to modulate important disease parameters not only in HIV, but also in other inflammatory conditions like inflammatory bowel disease (IBD).
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Inflammation is a key component in HIV infection. We are still working towards fully understanding how ABX464 works, but believe that this anti-inflammatory activity could be a key contributing factor to the positive data obtain so far both in preclinical models and initial clinical studies in HIV. To explore this broadening of ABX464’s potential applications, ABIVAX is planning to start a clinical proof-of-concept study of ABX464 to treat IBD in 2017.
MedicalResearch.com: Is there anything else you would like to add?
Response: ABX464 is currently in Phase II clinical trials as a potential functional cure for HIV. It is a first-in-class, oral, small anti-viral molecule that blocks HIV replication through a unique mechanism of action – biogenesis inhibition of RNA used for viral replication. The top-line readout from a Phase 2a study evaluating whether ABX464 can maintain a low viral load in the blood of infected patients, which were treated with an established antiretroviral therapy and ABX464 or placebo, is due in April 2017.
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Disclosure: Study supported by ABIVAX
Preclinical Data presented at 2016 HIV DART (Frontiers in Drug Development for Antiretroviral Therapy) scientific conference in Los Cabos, Mexico.
Anti–HIV drug candidate ABX464 prevents intestinal inflammation by producing IL-22 in activated macrophages
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