The Journal of Infectious Diseases, December 2020
This exploratory study sought to determine whether romidepsin could awaken latent (‘sleeping’) HIV from its reservoir as part of an HIV cure “kick and kill strategy.” Romidepsin is a histone deacetylase inhibitor drug used to treat cutaneous T cell lymphoma.
In A5315, a randomized, double-blind, placebo-controlled study, investigators evaluated single doses of romidepsin at different amounts for three Cohorts. There were 43 participants with suppressed viral loads on ART that enrolled to prove this approach was safe. Sixteen participants were then enrolled in a final Cohort to receive romidepsin or placebo. Specialized techniques were used to look for HIV in different ways to see if the romidepsin worked.
All romidepsin doses were found to be safe and well-tolerated. However, there were no significant increases in HIV levels (meaning it did not activate sleeping HIV), and romidepsin did not appear to reawaken dormant virus from the reservoir at the doses studied, despite evidence that romidepsin had the expected effect on human cells.
Because studies of histone deacetylase (HDAC) inhibitors as single latency reversal agents, including this study, have failed to show a reduction in the inducible HIV-1 reservoir, other approaches will be needed to achieve a cure for HIV infection.
Bottom line: HDAC inhibitors like romidepsin will not get us closer to finding a way to eliminate the HIV in people. Negative studies like this help scientists move on to more promising approaches.
McMahon, D. K., Zheng, L., Cyktor, J. C., Aga, E., Macatangay, B. J., Godfrey, C., Para, M., Mitsuyasu, R. T., Hesselgesser, J., Dragavon, J., Dobrowolski, C., Karn, J., Acosta, E. P., Gandhi, R. T., Mellors, J. W., & ACTG A5315 Team (2020). A phase I/II randomized, placebo-controlled trial of romidepsin in persons with HIV-1 on suppressive antiretroviral therapy to assess safety and activation of HIV-1 expression (A5315). The Journal of infectious diseases, jiaa777. Advance online publication. https://doi.org/10.1093/infdis/jiaa777