Elite HIV Controllers and Hope for Treatment

Will people with HIV be able to do without antiretroviral therapy soon? According to l’Inserm, around 6,200 people are identified as seropositive every year in France. The vast majority of them will require antiretroviral treatment to control the virus and prevent the development of AIDS (which affects around 1,200 people each year in the country). But a small proportion manage to control the virus even without this treatment. Rare cases which intrigue experts, arousing in them the hope of understanding this mechanism of natural neutralization of the virus and thus reproducing it in other patients.

Several ways to attack HIV

According to Tae-Wook Chun, director of HIV Immunovirology at the US Institute of Allergies and Infectious Diseases, only 10 to 15% of patients who have been treated with antiretrovirals within six months of infection develop a sufficient immune response. to control the virus by bypassing their treatment. To elucidate the mechanism by which these patients neutralize HIV, Dr. Chun’s team followed two of these patients for five years, thanks to which they show that the virus can be controlled in various ways, in an article published in Nature Medicine October 28. “It was very interesting because these two patients were showing very different scenarios, he reveals to Sciences and the Future. The first had a high level of CD8 T cells versus virus, but very few neutralizing antibodies. He did not fully control the VIH so this one continued to evolve, causing sporadic episodes of reappearance of the virus. While it was the reverse with the second: he showed a very high level of neutralizing antibodies which managed to effectively control the virus for years, while his level of CD8 T lymphocytes was not particularly high. This is very surprising, because normally it takes several years for someone to develop such powerful neutralizing antibodies. ” Unfortunately, he was infected with another strain of HIV after four years, a strain his antibodies failed to control.

The elite of the elite controllers

Even rarer, there are patients who seem to eliminate all traces of the virus entirely. Two patients had already been able to completely eliminate HIV from their bodies, but only with the help of stem cells from subjects carrying a deletion in the CCR5 gene, a protective mutation against this virus. But in 2020 a team from the American Ragon Institute, belonging to Massachusetts General Hospital and MIT and Harvard universities, identified the first patient who would have achieved this without requiring this treatment. In an article published in Nature who studied patients who reduce the virus beyond detectable limits without the need for antiviral treatment (called elite controllers), they detected a patient who no longer had any of HIV genetic material, a 67-year-old Californian woman diagnosed with HIV in 1992. The same team identified a second such patient. in November 2021, a 30-year-old Argentine diagnosed with HIV in 2013, confirming that eliminating the virus naturally is rare but possible.

Seeking a cure to make all patients elite controllers

Thanks to these discoveries, experts hope to be able to reproduce this immune control in all HIV-positive patients. The key may be in the response of T cells against HIV. This is what the Tae-Wook Chun team attempted in 2017 with a experimental vaccine which was supposed to enhance the response of these cells, but unfortunately it did not show clinical efficacy. Despite this failure, the researchers do not despair and remain optimistic thanks to other attempts currently underway, such as the RNA vaccine designed by Moderna which is currently being tested in a phase 1 clinical trial or monoclonal antibodies. “We do not yet have a vaccine to prevent HIV transmission or to potentiate the immune response against the virus, but we are currently testing antibodies which work very well and which could suppress HIV with only two doses per year. unveils Tae-Wook Chun. I think that in a short time we will be able to control the virus without needing to use antiretroviral therapy.

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