[LUM#5] AIDS: A Molecule for a Better Life
For now, there is no cure. But is it possible to live a normal life despite having HIV? In Montpellier, the discovery of a new compound is offering hope.
1983: A team at the Pasteur Institute isolated the “human immunodeficiency virus,” or HIV, in a laboratory for the first time—a virus that attacks the immune system and gradually destroys it. This discovery marked the beginning of a dark decade. At the time, researchers struggled to combat the complex mechanisms of a disease that was tantamount to a death sentence.
Triple Therapies and Side Effects
A decisive step was taken in 1996, when a combination of three treatments was introduced to the market for the first time: the famous triple therapies. “Their introduction was a blessing for patients whose previous treatments had failed, as they helped minimize the virus’s resistance to treatments that had previously been administered as monotherapies,” explains Jamal Tazi, a researcher at the Institute of Molecular Genetics in Montpellier. This was a major breakthrough, though it remains limited by a host of side effects: headaches, diarrhea, vomiting, accelerated tissue aging, inflammation, and bouts of fever…
In addition to the physical consequences, there is social exclusion and the obligation to undergo treatment—every day, for the rest of one’s life… But the key point is this: for the first time, HIV has gone from being a fatal disease to a chronic one. A disease that, when detected and treated early, no longer threatens patients’ lives.
Provide relief to patients
Twenty years and millions of victims later, a cure for the disease is still elusive. The only confirmed case of a cure is that of the now-famous “Berlin patient” in 2007 . But the story of this American, Timothy Brown, is very much an exception that proves the rule. “This was a patient who received a transplant using cells carrying a mutation in a gene that happens to be a receptor for the virus, CCR5. But this is an exceptional, fortunate, and somewhat mythical case that has never been replicated since,” explains the geneticist.
While a miracle cure is not on the horizon, research today is focusing on new approaches. “The researchers’ goal today is very clear: to find drugs with a new mechanism of action to replace triple therapies, which have shown their limitations,” summarizes Jamal Tazi.
Among the most promising avenues is that of a “functional cure .” “It’s no longer a matter of eradicating the virus from the body—which seems unrealistic—but of suppressing its expression. “What we hope to achieve in the long run is to free patients from the need to take medication every day,” explains Jamal Tazi. Having become the be-all and end-all of HIV research, the quest for this functional cure is precisely at the heart of the work being conducted by the IGMM researcher. And this molecular discoverer may have struck gold: ABX464 ( “First Evidence of Antiviral Activity and Safety of ABX464 in Treatment-Naïve HIV Patients,” in Journal of Virus Eradication, 2016).
Limiting the “rebound effect”
This molecule, whose role is to prevent the production of viral RNAs responsible for viral replication, has a unique property that could make all the difference: its ability to keep the viral load at a very low level, even several weeks after treatment has stopped. ABX464 could thus counteract the so-called “rebound effect”—that is, the rise in viral load when medication is stopped—which is the main obstacle on the path to a functional cure.
“The treatment is still in the trial phase, but so far we have observed that ABX464 sustainably reduces the viral load in patients, without any side effects. This is very encouraging. Our work has also been very well received by the scientific community.” A less burdensome treatment that needs to be taken less often—that is the prospect opened up by the discovery of this molecule, developed in Montpellier at a joint laboratory involving teams from the IGMM and the biotechnology company Abivax.
How often will patients need to take this treatment: once a week, once a month, or every six months? That is what the Phase 2 (of 3) clinical trial currently underway aims to determine; results are expected in April 2017. While we are still a long way from market approval—which is not expected for several years—the compound discovered by the IGMM offers hope that was once considered a pipe dream: living a normal life with AIDS.
In Montpellier, on the trail of HIV
Where did the AIDS virus first appear? How did the disease jump from monkeys to humans? Researchers at the international laboratory“Translational Research on HIV and Infectious Diseases”have finally found the answers to these mysteries. By tracing the virus’s path, they identified for the first time, in 2014, the geographic epicenter and point of origin of HIV-1, the main variant of HIV. This massive treasure hunt was solved by cross-referencing hundreds of HIV samples with socioeconomic data. The researchers thus demonstrated that it was in southeastern Cameroon, around 1920, that the retrovirus was first transmitted from its original host—the monkey—to humans. The researchers were then able to trace the dynamics of the disease’s spread, showing how it traveled from its birthplace in the tropical forest to Kinshasa, the starting point of an epidemic facilitated by the development of river and rail transportation (documentary *AIDS: On the African Trail*).
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