Nature: Ученые из Франции рассказали о 12-летней ремиссии после отмены АРВ-терапии
A French teenager who was infected with HIV at birth has lived in good health an astonishing 12 years since she last took antiretroviral drugs, researchers say. The case — the longest-known example of a paediatric HIV patient living without ill effect after discontinuing treatment — adds to the overwhelming body of knowledge supporting the benefits of early treatment, and will help researchers to better understand why some patients with HIV can go into remission after ceasing treatment.
Scientists described the case of the unidentified girl, who is now 18 and a half years old, today (20 July) at the annual meeting of the International AIDS Society in Vancouver, Canada. She joins a select group of patients with HIV — such as the 'Mississippi baby'1 and the 'VISCONTI cohort' of 20 patients2 — who were treated early on in their infections, then discontinued treatment without immediate ill effects.
These patients are a very rare exception to the rule, doctors caution: the vast majority of patients with HIV who stop treatment experience a rebound in virus levels that, if left untreated, can harm their health.
“It’s an intriguing case, but it’s a very unique and unusual outcome,” says physician and virologist Deborah Persaud of Johns Hopkins Children’s Center in Baltimore, Maryland, who first reported on the Mississippi baby in 2013. “We’ve had many kids who are treated for years, then go off treatment and rebound, so the global message is still that kids should stay on treatment.”
Adults in the VISCONTI cohort controlled the virus without drugs for a median of 10 years before the virus rebounded, and the Mississippi baby controlled the virus for just over 2 years before it rebounded when she was almost 4 years old.
Because of that history, reaction to the French case has not been as elated as it was when the Mississippi baby was first described.
“At some point, the idea of remission was mixed with the idea of cure, and expectations were too high,” says translational researcher Asier Sáez-Cirión of the Institut Pasteur in Paris, who presented the French teenager’s case today. He says of the girl’s family: “They understand that this is not a cure, that this is state of remission, and that we don’t know exactly what happened.”
Some scientists still say it is not clear whether the French teenager, the VISCONTI adults or the Mississippi baby — so-called 'post-treatment controllers' — could have controlled the virus on their own if they had never been treated. About 1% of patients with HIV — who are known as 'elite controllers' — can control the virus despite never starting treatment. That group shows different genetic and immunological characteristics from the post-treatment controllers.
“It seems like something is different” between post-treatment and elite controllers, says virologist Steven Deeks of the University of California, San Francisco. But, he says of the French teenager and other post-treatment controllers, “it’s impossible to prove that they would not have done well in the absence of therapy.”
Like the Mississippi baby, the French teen became infected by her mother at around the time of her birth. But there are some crucial differences between the timing and dosing of the treatment regimens the children received.
The American girl was started on highly active antiretroviral therapy — a combination of powerful medicines designed to control HIV — within 30 hours of birth. By contrast, the French patient was initially treated for 6 weeks with a single drug, zidovudine. When her viral load shot up at the age of 3 months, she started a combination treatment with four antiretroviral drugs.
But her family decided, for reasons that have not been made public, to discontinue the French girl’s treatment when she was between 5 and 6 years old. Even so, when doctors then saw her as a 6-year-old, she was apparently healthy, with an undetectable level of HIV in her body. Twelve years later, she is still healthy despite not taking medication for HIV.
“This case is clearly additional evidence of the powerful benefit of starting treatment very early on,” says virologist Françoise Barré-Sinoussi of the Institut Pasteur in Paris.
Why this girl has fared better to date than the Mississippi baby and most patients with HIV is not clear, and is a topic of intense scrutiny. A major goal for the HIV field is understanding whether there are characteristics that might be used to predict in advance which patients will fare well if their treatment is discontinued.
The French teen is now being studied as part of the VISCONTI cohort. Eighteen of them remain drug-free. Only 5–15% of people who start early treatment are able to remain in control of the virus after discontinuing treatment in this way.
The French girl and the other VISCONTI patients share particular variants of immune genes that actually seem to predispose them to particularly severe early HIV infections. Researchers aren't sure how this might be connected to them becoming post-treatment controllers; it may cause their infections to be noticed earlier, and thus be treated earlier, than in other patients. That sets them apart from the elite controllers, who in contrast seem to have genetic traits associated with greater ability to control the infection.