Joel Pomerantz of Biological Chemistry
on his collaboration with Robert Siliciano
in eliminating HIV:
So what is the current state of HIV treatment? It seems that, at least in developed nations, it’s not quite the dramatic killer it used to be.
POMERANTZ: HIV treatment has improved considerably over the years, and today’s widely-used HAART (highly active anti-retroviral therapy) regimen is very effective in reducing viral loads. The problem is that patients have to remain on HAART for many years, which raises issues of cost, potential drug resistance and tolerance of the therapy.
And treatment does not equal cure?
POMERANTZ: Right. HAART and other drugs do not fully eliminate HIV because a small subset of cells remain latently infected and untouched by therapy. Once you remove the therapy, the virus bounces back pretty quickly. So we still have whole armies of researchers working on vaccines, prevention and other approaches for eliminating HIV.
Bob Siliciano is a world authority on this issue of HIV latency. I have been lucky to collaborate with Bob and one of his talented students, Hung-Chih Yang, on a project trying to eradicate latent HIV. I was drawn to it because T cells are often the host for latent HIV.
How does one remove latent virus?
POMERANTZ: Well, our goal is not to remove the integrated DNA, but instead convince latently infected cells to turn on the HIV genome at which point they might be killed by drug treatment or natural immune mechanisms.
Some researchers have tried this approach using general activators of T cell function, but global T cell activation can be toxic. So our question has become, “How can we turn on HIV in a latently infected T cell without activating the immune function of the cell?”
And how are the efforts progressing?
POMERANTZ: We are in the very early stages. Our strategy has been to apply the screening approach I used to identify CARD11 to search for genes that can turn on the HIV genome without turning on T cell genes important in immune function. And we have found one that looks promising. We have a lot of work to do before our efforts can be translated into therapy, and we are hoping to share our strategy with other researchers in the field.