'Post-Treatment Controllers' Offer a Glint of Hope for a Functional HIV Cure

The term is "post-treatment controller." A recently diagnosed HIV patient, the future controller, is started on anti-retroviral treatment immediately—contrary to some earlier, mostly rejected protocols, which delayed treatment until the virus accumulates—and they remain on that treatment for several years, after which they stop. In a post-treatment controller, the virus stays suppressed and the patient is able to live a healthy life—not cured, but at least drug-free. Why this happens in some seemingly very lucky patients is an enduring mystery.

At the The 8th IAS Conference on HIV Pathogenesis, Treatment and, Prevention this week in Vancouver, Asier Sáez-Cirión, an epidemiologist and infectious diseases specialist from the Pasteur Institute in Paris, is presenting the case of one young French woman who, after stopping HIV treatment as a child, has managed to continue on for 12 years healthy and treatment-free. While still present in her body, the virus has nonetheless remained suppressed and no one quite knows why. She is still alive.

The French patient isn't alone. In 2013, Sáez-Cirión published a paper describing 14 patients, known as the VISCONTI cohort, who have likewise remained in a state of perpetual viral suppression since ceasing antiretroviral treatment. Including this latest addition, the VISCONTI group is now at 20 members—all healthy, all without treatment.

Sáez-Cirión's work with the VISCONTI group is concerned with its relationship to another seemingly very similar category of HIV patient. These are the "elite controllers," a group marked by the same treatment-free long-term suppression of the virus, but with one huge difference: They were never treated. The elite controllers, also known as long-term non-progressors, were at some point infected, but with no intervention they've managed to keep the virus in check. This group makes up about 1 percent of all HIV infections. As with the post-treatment controllers, the mechanism behind the elites is mysterious.

In the new study, the Pasteur Institute researchers examined in detail the immune responses of the different groups of controllers, in particular their relative abundances of CD4 and CD8 T cells and the proteins that trigger their production. A portion of the elites are genetically predisposed to having high levels of CD8 lymphocytes, which kill off HIV-infected cells. Which makes sense, of course: the better an immune system is at killing off HIV, the less HIV is likely to be found.

But there's an interesting twist when it comes to the post-treatment controllers. They tend to have weaker immune systems in the first place. Science explains:

Sáez-Cirión's work puts into the spotlight the concept of a "functional cure." This isn't a cure in the sense of ridding the body of HIV entirely as it is in arming the body to keep HIV in check for long periods of time, possibly a lifetime. Given the still dim possibility of an actual practical (or at least safe) cure-cure, and the arduous and side effect-prone barrages of pills patients usually require to keep the virus in check, a functional cure seems pretty appealing, albeit maybe not so much for drug companies in the anti-retroviral business.

"Combination antiretroviral therapy reduces HIV-associated morbidities and mortalities but cannot cure the infection," Sáez-Cirión and his group wrote in the 2013 study. "Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. Our results show that early and prolonged [anti-retroviral therapy] may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure."