As mentioned earlier in this issue of TreatmentUpdate, the anti-cancer drug romidepsin (Istodax) can also inhibit the activity of HDAC (histone deacetylase), an enzyme that can help keep HIV infection latent.

Researchers with the pharmaceutical company Gilead Sciences performed laboratory experiments with cells extracted from 46 HIV-positive ART users whose CD4+ counts were above 350 cells and viral load less than 50 copies/ml. Specifically the researchers tested the following HDAC inhibitors:

  • romidepsin
  • panobinostat
  • givinostat
  • vorinostat
  • mocetinostat

Romidepsin appeared to be the most potent HDAC inhibitor in these test-tube studies. Its ability to bring HIV out of latency was consistent over time with cells from the same or different donors.

Regulatory authorities in the U.S. have approved the use of romidepsin, given intravenously at a dose of 15 mg per square metre of skin surface, for the treatment of certain cancers. However, according to the Gilead experiments, much lower doses can be used when attempting to bring HIV out of latency. These lower doses range between 2 and 5 mg/m2.

Based on these promising but preliminary experiments, expect a clinical trial of romidepsin in the future.

REFERENCE:

  1. Kent SJ, Reece JC, Petravic J, et al. The search for an HIV cure: tackling latent infection. Lancet Infectious Diseases. 2013; in press.
  2. Katlama C, Deeks SG, Autran B, et al. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet. 2013; in press.
  3. Wei G, Chiang V, Fyne E, et al. Histone deacetylase inhibitor romidepsin induces HIV in resting CD4+ T cells from ART-suppressed subjects at concentrations achieved by clinical dosing. In: Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections, 3-6 March 2013, Atlanta, U.S. Abstract 376.