Study debunks valproic acid as HIV cure

A group of Johns Hopkins researchers has found that a drug that was thought to offer a key to eliminating HIV from the body permanently in fact does no such thing. Apparently, it's back to the drawing board for an HIV cure in a pill.

Valproic acid is an anti-epilepsy drug that was recently found to act against an enzyme that keeps HIV in a dormant mode inside cells. Essentially, valproic acid removes proteins called histones that act like knots in the string of the cell's DNA; histones stop DNA from dividing. Take away the histones, and you get an active cell churning out HIV.

Why would you want to make a cell produce HIV? The theory was that the reason we can't get rid of HIV from the body right now is because a small amount of it stays locked up in the genes of dormant immune cells. These cells get activated so rarely—normally only in response to infections—that the body keeps a permanent reservoir of HIV deep inside the gene code of the immune system where conventional HIV drugs can't get to it.

The hope was that if valproic acid could force all the HIV-containing cells in the body to switch on and start producing HIV, while containing the harmful effects with conventional antiretrovirals, you might drain the reservoir. A 2005 study promised exactly that result: David Margolis gave four patients valproic acid alongside HIV drugs for three months and found that the amount of HIV in their resting cells decreased in three out of the four by 68% to 84%. But even Margolis warned that you'd have to get rid of the HIV in at least 99,999 of every 100,000 cells to really rid the body of it.

A new study has flatly contradicted Margolis's results and concludes that valproic acid has no effect on the reservoir of HIV. Janet Siliciano of Johns Hopkins University in Baltimore measured the amount of hidden HIV in nine patients who were already taking valproic acid for neurological problems alongside HIV drugs for at least three months.

In contrast with the 2005 study, Siciliano found that the amount of HIV in dormant cells did not decrease over time and that if it was decreasing at all, it would take over 60 years on continuous antiretroviral therapy with no treatment breaks for all the hidden HIV in the body to be eliminated.

However, she praised the Margolis study for at least going in the right direction and trying to target HIV where it's hardest to get at—spliced into the body's own genes.

There are a number of other experimental approaches to finding a cure for HIV. These include small interfering RNAs, which are "scrambler" molecules that mess up the instructions for making new viruses; injecting special "HIV-proofed" immune cells into the body; and therapeutic vaccines that cause the body to kill off HIV-infected cells. (Gus Cairns, Gay.com/U.K.)