Valproic acid, a commonly used drug for epilepsy, migraine and bipolar disorder, could also have a role to play in the control of HIV by tackling dormant virus particles, according to US researchers.
During HIV infection, some virus particles will be actively dividing, while others lie dormant in cells in the lymph nodes or other parts of the body. Because current antiretroviral drugs are only designed to kill virus that is actively replicating, dormant HIV evades treatment and will quickly re-establish itself if a patient stops taking a cocktail of drugs known as HAART (highly-active antiretroviral therapy).
Valproic acid blocks an enzyme called histone deacetylase 1 (HDAC1) that keeps HIV in a latent, non-replicating state, and in vitro studies have already shown that the drug can stimulate the release of HIV from dormant cells. Now, the US scientists report in The Lancet (August 13 issue) that a combination of Abbott Laboratories’ Depakote (divalproex sodium) formulation of the drug and Roche’s HIV entry inhibitor Fuzeon (enfuvirtide) – given on top of HAART - can reduce latent HIV infection by 75% in three of four patients tested. In the fourth patient, latent HIV was reduced by around a third.
Depakote, which already makes sales in excess of $1 billion dollars a year, was given to mobilise latent HIV and expose it to the effects of HAART, while Fuzeon was given in tandem to prevent the patient from the consequences of this escalation in HIV infection, said the researchers, from the University of North Carolina.
While preliminary, the data suggest that it may be possible to eradicate HIV through a combination of HAART and HIV-mobilising therapy, although the authors stress that their pilot study “is limited and leaves many questions unanswered.”