What can post-treatment controllers tell us about HIV care and treatment?
by Jeannie Wraight
In order to keep their virus suppressed, most people living with HIV must take antiretrovirals (ARVs) daily. If ARVs are stopped, an increase in viral load to detectable levels is usually seen after three to four weeks. However, a small group of HIV-positive people are able to discontinue therapy without viral rebound for an extended period of time. These people are referred to as post-treatment controllers.
At one time, HIV antiretroviral therapy consisted of many pills taken several times a day. Despite a massive reduction in the number of pills, current HIV regimens—even one-pill-a-day regimens—can be difficult to maintain on a daily basis due to side effects, co-morbidities, high cost, stigma and/or difficulty remembering to take one’s pill(s). Also for some, having to take ARVs every day is a constant reminder that they’re living with HIV and makes adherence more difficult.
Researchers are developing ARVs that can be taken less often then the daily medications that people living with HIV currently must contend with. Long-acting ARVs are in development and they may allow for weekly or even monthly injections in lieu of daily dosing.
In addition to long-acting ARVs, researchers are also looking at a small group of individuals with HIV who are able to maintain an undetectable viral load after discontinuing therapy. Post-treatment controllers may offer clues to develop strategies and new drugs that could help others to better control HIV and allow for less frequent use of ARVs.
Descriptions vary, but one definition of post-treatment controllers is those who are able to maintain viral loads of 400 or fewer copies per milliliter of blood for at least twenty-four weeks after stopping HIV therapy. An exact percentage of people who are able to control their virus is unknown, but researchers estimate the number to be between five and fifteen percent of people living with HIV. However, as most people on ARVs don’t interrupt their therapy, it is difficult to know exactly who or how many actually belong to this group.
Post-treatment controllers are different from “HIV controllers” who are able to maintain undetectable viral loads without ARVs. Less than one percent of people living with HIV are thought to be HIV controllers.
There are several well known cases of post-treatment control. Most notably, the VISCONTI cohort. VISCONTI stands for Viro-Immunologic Sustained Control After Treatment Interruption. The VISCONTI cohort was a group of fourteen Italian people living with HIV who began ARVs within ten weeks of HIV infection. They remained on ARVs for a minimum of three years and, after discontinuing treatment, were able to suppress HIV to undectable levels for an average of seven and a half years.
The “French teenager” is another well documented case. The girl was born with HIV and received prophylactic ARVs shortly after birth (though the exact time frame is unclear). She remained on treatment for six years. At the time of the most recent report in 2016, she had remained off therapy with an undectable viral load for twelve years.
Very early treatment after HIV infection as in the VISCONTI cohort and the French teenager is thought to possibly limit the establishment of viral reservoirs . However, a very small handful of cases differ greatly from the others in as they were positive for some time before initiating antiretroviral therapy.
In 2011 a (then) fifty-one year old Argentinian woman was reported to have discontinued ARVs in 2007 after eleven years of treatment. In addition to having started ART a substantial period of time after HIV infection, the Argentinian woman had been defined as having AIDS before she began taking ARVs. In fact, she was quite sick before initiating therapy, unlike nearly all other cases of post-treatment controllers who began ARVs very early on after their initial infection with HIV.
A study in 2018 described three individuals who were also considered “chronically infected” and were able to control their virus after stopping ARVs. It’s unclear whether the Argentinian woman is among the three people studied.
As it’s now standard of care to begin ART immediately following diagnosis and remain on treatment indefinitely, how would we be able to tell who is a post–treatment controller? One study published last year examined post-treatment controllers in hopes of determining characteristics that may help to identify who may belong to this group. They found that post-treatment controllers had smaller viral reservoirs and that reservoir size may be a useful biomarker in determining who may be a post-treatment controller.
More studies on post-treatment controllers could help to establish if a person needs to be on lifelong ARVs or if they belong to the small group of people living with HIV who are able to stop HIV treatment and remain undectable. Further studies could potentially also offer clues for the development of drugs and strategies to help others maintain temporary viral suppression after discontinuing ART.
Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody.com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.