Raiding the reservoir

AIDS Researcher David Ho reports on “hidden HIV” and potential new avenues of attack.

In 1996, when Time magazine named David Ho, M.D., as its man of the year, people with AIDS were enjoying the first glimmers of hope for long-term survival, thanks to the combination therapies he and others helped develop. They were living longer, and the new treatments kept many with HIV from developing full-blown AIDS.

Three years later, however, that optimism has waned as the limitations of those therapies have become apparent. Although mortality due to AIDS has decreased five-fold over the last several years, the new treatments don’t work for everyone. Strains of HIV are now resistant to the medications. And survival means a life ruled by rigorous adherence to an unforgiving schedule of foul-tasting pills.

Ho, director of the Aaron Diamond AIDS Research Center in New York City, described the next steps in the battle against AIDS at the first T.S. Lin Memorial Lecture, sponsored by the Department of Pharmacology. In his talk, Advances and Obstacles in HIV Therapy, Ho said that studies have found that although some patients have apparently undetectable levels of HIV, pools of the virus remain, lodged in immune cells called memory Cd4 lymphocytes. “The level of replication of the virus, we think, is exceedingly low,” Ho said. “One has to come up with a strategy that would facilitate the decay of the reservoir.” His approach, still under study, is to activate the immune system’s resting Cd4 cells to keep the pool of virus in check. “We think it would be very difficult to drive this pool to zero,” he said. “We could drive it sufficiently low that we could ask the immune system to clean it up and keep it under control.”

The lecture series honors Lin, a pharmacology research scientist who died in 1992 and collaborated with William H. Prusoff, Ph.D., professor emeritus of pharmacology, to develop the anti-retroviral compound d4T as a treatment for AIDS. Marketed as Zerit, d4T has helped to prolong many thousands of AIDS patients’ lives. Ho was introduced by Yung-Chi Cheng, Ph.D., the Henry Bronson Professor of Pharmacology and Medicine, who helped develop 3TC, another AIDS treatment.