HIV Eradication Trials: where are we going?
An interview of David Margolis, University of North Carolina, Chapell Hill, USA
At a time when hope for HIV eradication is again in the news, following the publication of the 'Berlin patient', we have asked to a renowned specialist what the perspectives really are.
Q1: Some scientists doubt an HIV cure will ever be achieved. Are you still an optimist and why?
DM: I never know how to answer such questions, just as I do not know what to say when people ask when we will accomplish this feat. The goal of eradicating virus in a person, or allowing the safe interruption of ART (so-called “functional cure”) seems difficult but possible. I am optimistic that if we pursue this goal we will learn important and useful things, and improve the lives of people with HIV infection.
Q2: What have we learned in terms of HIV persistence since you first tried to purge the HIV reservoir with valproic acid 5 years ago?
DM: We have learned a great deal about the many molecular mechanisms that restrict HIV expression and allow for persistence of virus, and about the persistent expression of virus in patients on stable ART. But we have not yet learned to translate this understanding into more effective approaches to purge latent HIV. That is the next challenge.
Q3: What are, in your view, the more promising drugs to be tested in the near future for this ‘purge’ approach? What are your short-term projects?
DM: We hope to test SAHA of vorinostat soon, a potent HDAC inhibitor.
Q4: Do you think that a chemical compound could be enough to reach an HIV cure or remission, or that an immunologic complement –as a vaccine- or another approach – like stem cell gene therapy- will be needed in addition to control the very last few cells with latent HIV?
DM: I think that a chemical approach alone might succeed, but that a combined approach that also has an immunological component might improve the chances of success.
Q5: Are drug companies actively looking for compounds able to cure HIV? Are governments and foundations actively involved in this area of research?
DM: Yes, but it could be argued that this area is not sufficiently funded.
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Key words: HDAC, hiv cure, hiv eradication, hiv eradication trials, vorinostat