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HIV "Functionally Cured" In 14 Adults Treated Early

A new study shows that 14 HIV-infected adults appear to be "functionally cured", that is they still carry small, barely detectable reservoirs of the human immunodeficiency virus but their bodies are preventing them from rising to a point where they cause symptoms, despite stopping treatment. Researchers believe the key to achieving this remarkable result may be to start treatment as early as possible after infection.

First author Asier Sáez‐Cirión of Institut Pasteur, Paris, and colleagues, report the result of following the 14 patients, known as the VISCONTI cohort, in a research paper published online in PLoS Pathogens on 14 March.

VISCONTI stands for Viro-Immunologic Sustained Control After Treatment Interruption. The study was funded by the ANRS, the French National Agency for Research on AIDS and Viral Hepatitis.

The researchers started monitoring the 14 adults when they received antiretroviral drugs, which was within 10 weeks of becoming infected with HIV. The patients stopped treatment, on average, about three years later (the drugs were withdrawn under medical supervision).

So far, say the researchers, the patients have been able to keep viral loads in check for a median of 7.5 years without further drug treatment.

One of the reasons HIV has proved to be so difficult to deal with, is that after an acute infection, the virus sets up reservoirs in host cells that allow it to hide and return. Even after years of treatment, once the drugs are withdrawn, most patients see the infection return.

But, there is a very small minority of HIV-infected patients (under 1%) in whom the virus virtually disappears, without the help of treatment. Known as "HIV controllers", these patients spontaneously vastly reduce their viral load and maintain long term control of the virus, to practically undetectable levels.

So researchers, like those following the VISCONTI patients, have wondered whether it may be possible to transfer the HIV controllers' mechanisms to other patients.

However, what the VISCONTI trial reveals, is that there appears to be another group of people, that the researchers call "elite controllers", or "post-treatment controllers" (PTCs), genetically distinct from HIV controllers, whose bodies still have detectable levels of HIV years after infection, but when treatment is withdrawn these levels remain in check, and don't rise to a point where they cause symptoms.

So while elite controllers are not "cured" in the sense that HIV controllers seem to be, they are "functionally cured" in that they still carry a a barely detectable amount of HIV but not so much that it causes disease.

The researchers say the elite controllers appear to have achieved control through mechanisms that are not necessarily the same as those that spontaneously "cured" the HIV controllers.

They suggest starting antiretroviral therapy during the "primary" stage of infection could be the key, because it seems to reduce viral reservoirs, preserve patients' immune responses, and protect them from chronic immune activation.

Some of the 14 patients not only kept their low viral loads in check, they also managed to reduce them.

"This might be related to the low contribution of long-lived cells to the HIV-reservoir in these patients," write the researchers.

They estimate that probably aroud 15% of HIV-positive people may potentially be able to respond like elite controllers, as long as they are treated early enough. This is considerably higher than the under 1% cured via spontaneous control, they note.

Another recent study reports for the first time that an HIV-positive baby treated soon after birth has been functionally cured. At the time of reporting results, the baby was 2.5 years old, and showed no sign of functioning virus.

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