Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults with HIV

Clinical Infectious Diseases, March 2021.

Inflammation is a serious concern among people living with HIV, as it is associated with increased occurrence of other health conditions and death. Ruxolitinib is an anti-inflammatory medication that has reduced inflammation in people without HIV and lowers indicators of the HIV reservoir (the amount of HIV still within a person even though they may have an “undetectable” viral load) in laboratory studies. A5336 was an open-label, multi-site, randomized-controlled trial that evaluated the addition of ruxolitinib (10mg twice a day) to stable ART for five weeks compared to ART alone, in an effort to determine its safety and efficacy among people living with HIV on ART. Eligible participants had been virally suppressed on ART for more than two years without other health conditions and had >350 CD4+ T-cells. Study endpoints were discontinuation of ruxolitinib, safety events, and changes in measures of inflammation and the HIV reservoir. Ultimately, the study showed that ruxolitinib was well-tolerated by healthy, virologically suppressed people living with HIV on ART. Although there was no significant reduction in IL-6, the primary inflammatory marker endpoint (whose baseline levels were normal), ruxolitinib did significantly decrease other markers of inflammation. Future studies of this class of medications should target people living with HIV who have residual inflammation despite suppressive ART.

Summary and Implications: Ruxolitinib is not ready to be used in people living with HIV to decrease inflammation. It may be more helpful in people who show clear signs of inflammation, but this needs to be tested. We are still searching for the best way to address excess inflammation in people living with HIV.

Marconi, V. C., Moser, C., Gavegnano, C., Deeks, S. G., Lederman, M. M., Overton, E. T., Tsibris, A., Hunt, P. W., Kantor, A., Sekaly, R. P., Tressler, R., Flexner, C., Hurwitz, S. J., Moisi, D., Clagett, B., Hardin, W. R., Del Rio, C., Schinazi, R. F., & Lennox, J. J. (2021). Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults with HIV. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, ciab212. Advance online publication. https://doi.org/10.1093/cid/ciab212