Post-Treatment Controllers: Pathway to a Functional Cure?

Recent reports of a French teenager in remission from her HIV infection for 12 years serve as an important reminder that a functional cure for HIV is attainable. This case, presented at the International AIDS Society (IAS) conference in Vancouver, represents the longest reported instance of remission.  Other cases of remission have also been reported and seem to be an outcome associated with between 5% and 15% of HIV-infected persons who start combination antiretroviral therapy (cART) early during acute infection.

  Dr. Mirko Paiardini (Photo copyright Steve Forrest/Worker’s Photos/IAS)

Dr. Mirko Paiardini (Photo copyright Steve Forrest/Worker’s Photos/IAS)

These patients, known as post-treatment controllers (PTCs), are different than elite controllers, the roughly 1% of HIV-positive individuals who are able to control their HIV infection to undetectable levels without the use of antiretroviral therapy. The majority of HIV-positive individuals can only manage their viral load with the use of cART. Once the drugs are stopped, HIV comes roaring back and is readily detectable in their blood. PTCs, however, are able to control their HIV infection even when treatment is stopped. Starting cART early seems to be the key to their immunologic control, but how exactly their bodies are able to lock down HIV is an area of active investigation.

Mirko Paiardini, an amfAR-funded investigator at Emory University in Atlanta, is trying to solve this mystery by establishing an animal model to study PTCs. Dr. Paiardini presented data at the IAS conference that described a primate model mirroring the virologic and immunologic features of human PTCs. Animal models are crucial to understanding the biological mechanisms at work in PTCs and can contribute to our understanding of how a functional cure might be achieved in humans.

Dr. Paiardini’s amfAR-funded studies also aim to address whether the latent viral reservoir can be diminished by treatment with the immune modulator, IL-21. This viral reservoir is the single most important bottleneck that has prevented a cure for HIV and is the reason for HIV’s resurfacing in the majority of patients following cessation of cART. If Dr. Paiardini’s work succeeds in establishing IL-21’s role in shrinking the viral reservoir, we will certainly be one step closer to a cure.

Dr. Flores is amfAR’s associate director of research.