In a study of 29 virally suppressed patients who discontinued antiretroviral therapy (ART), every patient was able to maintain viral suppression from infusions of an antibody that blocks the HIV-binding site on CD4+ T cells.
Results of a phase 2 study are indicating that infusions of an antibody that blocks the HIV-binding site on CD4+ T cells may be able to suppress HIV for up to 4 months in patients undergoing a short-term pause in their antiretroviral therapy (ART).
Among the 29 virally suppressed patients in the study, every patient treated with UB-421 maintained viral suppression. There were intermittent viral blips in 8 (28%) patients, ranging from 21 to 142 copies per millimeter, but no patient had plasma viral rebound to more than 400 copies per milliliter.
“This is another modest advance in the tools that we now have in our armamentarium to treat people with HIV,” said Anthony S. Fauci, MD, director of the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, in an interview with The American Journal of Managed Care®.
Unlike previous approaches using broadly neutralizing antibodies (bNAbs) against HIV, UB-421 is directed at the receptor of the virus on the cell, Fauci explained. Typically, infusions of bNAbs have suppressed HIV for 2 weeks by targeting the HIV virus itself, but the method has led to the development of antibody-resistant virus in the absence of ART.
According to Fauci, these findings have implications for 3 types of patients, including those who experience ART resistance and those who experience ART-related toxicity. It also has implications for patients with pill fatigue who, despite doing well on their ART regimen, experience psychological push back from the daily reminder of infection.
“There is a subset of people who would prefer to come in at certain intervals and get an infusion of an antibody that can effectively suppress the virus and get them off the requirement of a single pill or a few pills a day of antiretroviral drugs, and that’s exactly what this particular antibody does,” he said.
Upon enrollment in the study, patients discontinued their normal regimens of ART at the time of infusion or 1 week later, depending on their regimen. While 14 of the patients received 8 regular weekly infusions of UB-421 (10 mg per kg of body weight), 15 received 8 higher-dose infusions every other week (25 mg per kilogram of body weight). Following the end of the 8- or 16-week periods, all patients resumed treatment with their ART regimens.
Rash, mostly grade 1, was a common and transient adverse event, with 1 patient discontinuing infusions as a result.
Looking forward, Fauci said that an extension of this study is needed due to the small sample size. Researchers will also likely modify the antibody so that patients can receive infusions at longer intervals, such as every 3 or 4 months, he said.
Wang C, Wong W, Tsai H, et al. Effect of anti-CD4 antibody UB-421 on HIV-1 rebound after treatment interruption [published online April 18, 2019]. N Engl J Med. doi: 10.1056/NEJMoa1802264.