Robert F. Siliciano's childhood love of chemistry was literally fueled by his mother, Ann, an anatomy and physiology professor at Elmira College.

"I had a lab in the attic, and my mom would get chemicals for me," he said. "I had liters of ether and benzene, concentrated hydrochloric acid, toluene. I had a Bunsen burner with a propane tank. My 'hood' was basically a large fan that blew the fumes outside!"

Siliciano (pronounced Sill-ih-CAH-noh) went on to major in chemistry at Princeton. Then, following his interest in medicine, he entered the M.D./Ph.D. program at Johns Hopkins. He earned his doctorate in immunology, studying how T cells recognize antigens (foreign particles). During a postdoc at Harvard, Siliciano was studying T cell responses to a synthetic antigen. His advisor, Ellis Reinhertz, urged him to "stop studying model systems and start studying a real antigen."

Siliciano chose HIV. He began studying the virus in the mid-1980s, just after it was identified. His discoveries about HIV have changed the way treatment is given.

HIV drug therapy—called highly active antiretroviral therapy, or HAART—has reduced AIDS mortality dramatically and morphed HIV infection from an acute disease to a chronic condition for many. The drugs can reduce the amount of circulating HIV to such low levels that it appears patients are cured. But the virus is still there. Where these few viral particles originate is still something of a puzzle, but Siliciano and colleagues have discovered two of the major pieces.

In 1997, Siliciano's group identified a population of HIV-infected memory T cells in patients on antiviral drug therapy. T cells are activated to defend the body against viruses or bacteria. Though most activated T cells die fighting the threat, a small subset becomes dormant. This subset serves as the immune system's lifelong "memory" against that particular threat.

Because antiviral drugs destroy HIV only when it replicates, dormant infected T cells aren't affected unless they are reactivated.

Memory T cell populations do change over time, but the changes are slow. Siliciano has estimated that these subsets of HIV-infected memory T cells could persist in one person for 70 years or more.

"Our findings made it clear that antiviral drugs will never cure anybody," Siliciano said.

Physicians used to prescribe an antiviral drug regimen as soon as possible after a positive HIV test, thinking they could eradicate the virus and cure the patient. In light of Siliciano's research, clinicians now focus on limiting drug side effects and reducing the chances of drug resistance. Rather than beginning treatment immediately, HAART is typically not started until the infection has progressed closer to the point where it starts having obvious effects on a person's immune system.

After discovering the infected T cell reservoir, Siliciano's group wanted to know if the virus in the blood of people on HAART was coming from infected T cells that had been reactivated. In a 2006 paper, Siliciano reported that the virus in the blood often was genetically different from the virus in the infected T cells. The research points to other reservoirs of HIV. Siliciano believes one of them may be a type of stem cell, but it has not yet been pinpointed. Whether HIV infects stem cells has been a controversial issue for many years. Siliciano's group hypothesizes that HIV may infect a progenitor cell in the bone marrow that gives rise to macrophages.

Besides searching for other viral reservoirs that prevent curing HIV infection, Siliciano hopes to better understand how the T cell reservoir is established and maintained. This knowledge may help develop new therapies against HIV-1 infection. His group is also working on drug resistance, a major problem in the treatment of HIV infection.