A drug developed to treat an unrelated blood disorder has shown impressive potential as an HIV treatment, according to a paper published Wednesday in the journal PLOS One by researchers from Rutgers University.
The medication, deferiprone, eradicates HIV-producing cells during treatment and limits their proliferation for at least eight weeks after drug administration was stopped. This persistence makes deferiprone unlike any antiretroviral drug on the market, all of which abruptly lose their effectiveness on treatment discontinuation.
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A key difference between deferiprone and current antiretrovirals is that it directly targets HIV DNA for destruction by prompting what’s known as a cell’s “altruistic suicide response.” By contrast, the mix of antiretrovirals delivered as part of normal combination antiretroviral therapy (cART) generally work by limiting the replication of HIV in the body to the point that the body’s own immune defenses can kick in.
“cART has the biological limitation of leaving infected cells intact to function as originators of HIV resistance and, upon treatment interruption, as drivers of HIV rebound,” the Rutgers group explains. “Without protective microbicides and effective vaccines, the effort to treat persons living with HIV-1 is locked into expanding the use of cART, a ‘more of the same’ strategy facing predictable exhaustion of the required massive injection of funds.”
So, in lieu of a cure, the HIV treatment holy grail is a medication that can remain effective in the body for an extended period of time. Given the current alternative of taking cART medications several times daily, eight weeks would be an eternity.
The effectiveness of deferiprone in nuking HIV wasn’t an accidental discovery—the first hints of deferiprone’s anti-HIV action appeared in 1998. The question the Rutgers researchers set out to answer was whether or not deferiprone can be effective enough to serve as an entry point into discovering/developing new anti-HIV drugs that work via the same mechanism, which would be huge.
Deferiprone works as an iron chelating agent, which means that it chemically binds to iron ions floating around in the blood (iron overload is a feature of thalassaemia, the disorder the drug is approved to treat). What this means for HIV is not all that obvious.
In lieu of a cure, the HIV treatment holy grail is a medication that can remain effective in the body for an extended period of time
The basic idea is that RNA transcription in HIV-infected cells occurs through a process that needs oxygen activation, which in turn needs the presence of iron. Deferiprone interferes with this in such a way as to fragment the HIV DNA, which the cell responds to eventually with apoptosis, or programmed cell death. Crucially, this interference occurs specifically in HIV-infected cells, while healthy cells are left alone.
The Rutgers study consisted of a proof-of-concept experiment using 26 subjects of mixed HIV status. The key finding is that HIV was unable to regroup within eight weeks of discontinuing treatment given a certain minimum dose threshold (so the drug goes from not working at all to working at a definite point, rather than increasing in effectiveness along a gradient, which is an important point).
Though it’s a mere footnote in the PLOS One paper, it’s worth noting that the researchers discuss the possible role of deferiprone in a curative scheme for HIV infections, which is something not spoken of lightly within the HIV research world.
“Current anti(retro)virals and regulations for their development do not seek to irreversibly remove the sites of virion production,” the study explains. “We identify deferiprone as the clinically established pioneer for this class of novel medicines, ablative anti(retro)virals. We propose that this class enables infected cells to reclaim their innate apoptotic proficiency, which renders the infective viral genome non-functional as a result of the medicine-facilitated suicide.”
That said, the Rutgers team is otherwise circumspect. This is still just a proof-of-concept, they note, and much work remains to be done in assessing the safety and efficacy of the drug in treating HIV infections. To that end, a somewhat larger study is currently underway in South Africa, but won’t be finished until August of this year. Actual published results will be still farther off.
