July 21, 2015
Jessica Handibode is an AVAC staff member.
Whenever I see or deliver a presentation about the state of HIV cure research one of the most interesting topics is how the field is defining what it means to be cured of HIV infection. Many researchers and community groups have pushed for the term “remission” to be used since there are no scientifically proven tests to determine whether an individual’s HIV will return. Recent cases of HIV “cures”—as they were reported in the media—like the two men from Boston and the Mississippi Child, have all ended in viral rebound. This further strengthens the case for the use of the term remission.
At the IAS 2015 conference on Monday, Dr. Asier Sáez-Cirión, of the Pasteur Institute in Paris, the same researcher working with the VISCONTI Cohort, introduced the world to an eighteen-year-old HIV-positive female living without treatment for over 11 years. This young woman offers a proof-of-concept for long-term control of HIV without treatment and pushes how the field might define remission of HIV.
What are the facts?
This young woman was born to a woman living with HIV who did not have viral control. Shortly after birth, the young woman was put on antiretroviral therapy and confirmed to be HIV-positive four weeks later. The mother reports that her daughter had challenges taking medication consistently during the first seven years of her life and that she stopped ART altogether twice.
During both treatment interruptions she experienced viral rebounds 75,190 copies/mL of blood & 97,000 copies/ mL of blood respectively. After both viral rebounds, she started treatment again and achieved virologic suppression. When the girl was about six years old, she stopped treatment and doctors’ visits. In research parlance, she was “lost to follow-up”. When the young woman returned to care a year later, she had an undetectable viral load. Since then, this young woman, who is now 18 years old, has remained undetectable without treatment except for two viral blips. Viral blips, or viremia, are periods where the number of viral copies rises above the limit of detection (40 viral copies/mL of blood). The first viral blip occurred at 11 years (509 copies/mL of blood) and the second at 14 years (48 copies/mL of blood). However she hasn’t been cured. In lab tests, HIV can be isolated and grown from cells from her blood.
What does this all mean?
Well, first it means that this young woman can control her virus without treatment, but her virus has not been eradicated. Since researchers can stimulate her cells to start producing virus in the lab, it is possible that she could experience another rebound. This is also supported by the two viral blips she experienced at 11 and 14 years old. In spite of this, she is capable of long-term virologic control—without ART.
Is she in remission or is she just controlling her virus?
She’s doing both! Long term post-treatment control has become a new area of discussion as cases like the VISCONTI cohort and this young woman are introduced to the field. The VISCONTI cohort, a group of French post-treatment controllers, were all treated early (within the first six months of infection) and were on suppressive treatment for a median time of three years before stopping treatment. The individuals in this cohort have been able to maintain control at very low or undetectable levels for about nine years off treatment. Post-treatment controllers differ from rare natural controllers known as “elite controllers” and “long-term non-progressors”. Both elite controllers and long-term non-progressors have protective immune responses that allow these individuals to control HIV without treatment. These individuals also have greater immune and inflammatory responses than HIV-positive individuals on ART. Remission, like cure, is a term with a specific emotional resonance. It is often thought about as the period of time where the disease is absent but could return. Both terms are fairly commonly used in the cancer field where, for instance, you are considered “in remission” for a certain number of years before you are “cancer-free”.
But there are so few cases of either remission or cure in HIV that it is very difficult to say when and how they should be used—or how to define them. With an individual like this young woman, it’s not possible to predict—because there are no comparators for her experience—when, if ever, she might have a rebound of HIV. She has been undetectable longer than the Berlin Patient has been cured, yet the presence of virus in her body means that she doesn’t meet the criteria for being cured. With so much uncertain science, the language sometimes fails us. But regardless of whether you describe this young woman as being in remission or a post-treatment controller, her experience pushes the science of HIV cure research forward and offers new hope for the future.