In a new trial, an experimental antibody suppressed HIV in patients on short-term pause from their daily antiretroviral therapy regimens.
Daily adherence to an antiretroviral therapy (ART) drug regimen is key to keeping people with HIV healthy, but a new study supported by the National Institute of Allergy and Infectious Diseases (NIAID) shows that a novel experimental antibody may suppress HIV levels for up to 4 months in people on a short-term pause from ART.
A study released by the National Institutes of Health (NIH) in January 2018 found that patients with HIV enrolled in clinical trial could have a short-term interruption from ART without damaging their immune systems or seeing a long-term increase in their viral load. The finding was key to the development of experimental therapies to induce sustained HIV remission without ART. In a new study published in The New England Journal of Medicine, investigators say that monotherapy with a novel antibody known as UB-421 worked to suppress HIV in participants for months and did not lead to antibody resistance.
In an interview with Contagion®, NIAID Director Anthony S. Fauci, MD, explained that there are 3 reasons why patients with HIV may seek an alternative treatment to ART—daily pill fatigue, unbearable toxicities against ART, and the development of resistance to standard ART.
“Right now in 2019 most people do very well with minimal toxicities, but some do want an alternative to ART,” explained Fauci. “So, if you fall into one of those 3 categories, there’s an intense interest in taking an intervention every few months with a single injection. If you perfect the antibody, it is conceivable that you can give the injection every 4 to 6 months. You’re talking about taking something 2 or 3 times a year versus a pill every day.”
The phase 2, open-label study was conducted in Taiwan and included 29 volunteers who were on daily oral ART and had well-controlled HIV, defined as plasma viremia of <20 copies of HIV RNA per milliliter. To participate in the study and begin receiving regular infusions of UB-421, volunteers discontinued ART. Of the study participants, 14 received 8 regular weekly infusions of UB-421 at a dose of 10 mg per kilogram of body weight, and 15 received 8 infusions at a dose of 25 mg per kilogram every 2 weeks. Participants then resumed their ART regimens at the end of the 8-week or 16-week treatment period, with follow-up evaluations up to 8 weeks later.
According to investigators, study participants in both groups maintained HIV suppression (plasma HIV RNA levels under 20 copies per milliliter) without ART during study period, though 8 participants had what the investigators called “intermittent viral blips” during the study (21 to 142 copies per milliliter), which Fauci says are normal occurrences in patients on ART. In addition, 1 participant discontinuing the trial due to a mild skin rash. UB-421 works by blocking a stable human protein that HIV uses to infect T cells, and the new study found that HIV did not develop antibody resistance to UB-421 as the virus has with other experimental broadly neutralizing antibodies.
“Most of the time the antibodies that we’re testing are what’s called broadly-neutralizing antibodies. Mainly they’re directed against the virus itself. The unique thing about this study is that it’s an antibody that’s not directed against the virus, but it’s directed against the receptor of the virus on the cell,” explained Fauci. “The results are pretty striking. As long as they get the antibody intermittently it seems to have durably suppressed the level of virus.”