HIV and AIDS were fully on the radar screen of national politics for the 1992 presidential election. Both parties had people with HIV give major addresses at their respective conventions: Mary Fisher, a heterosexual white woman, at the Republican National Convention in Houston, Texas, and Bob Hattoy, an openly gay man, at the Democratic National Convention in New York City. On January 20, 1993, Bill Clinton was sworn in as the forty-second president of the United States, and the Democrats now controlled both the House and the Senate. Hattoy was quickly appointed as a deputy in President Clinton’s Office of Presidential Personnel. With that came the hope of many activists that this would be an administration much more friendly and sympathetic to the needs of the at-risk community, as well as people living with HIV. Indeed, this expectation was in many respects met, particularly with regard to the access of gay activists to the White House. I was not sure yet what if any role I might have to play in the new administration. Shortly after being appointed secretary of HHS in early 1993, Donna Shalala telephoned me. Donna does not mince words, as I would quickly learn. “Tony, I just want you to know that you are my person for HIV/AIDS, and I am going to rely very heavily on you for advice and guidance. We have a lot of work to do.”
She was not kidding.
It had been clear since 1987 that a single drug alone (AZT) was not sufficient for the durable suppression of the replication of HIV. Combinations of two or even three drugs were significantly better. Even so, although the progression of disease was slowed, most patients continued to gradually deteriorate. We found out why when Michael Piatak, Jeffrey Lifson, and other researchers in 1993 developed a highly sensitive test for the level of HIV in the blood. Finally, we could measure to the lowest level the amount of virus that was produced in a person with HIV and precisely determine how effective the anti-HIV drugs were in suppressing the virus. The test told us that we were suppressing the virus substantially but not completely. This information was critical because as long as the virus was replicating, it was insidiously destroying the body’s immune system, making patients ever more susceptible to the host of complicating or opportunistic infections and cancers that were killing them.
As researchers developed additional drugs in the 1990s, we were also learning a considerable amount about how HIV affects the body and how the clinical disease of AIDS develops in a person. In my own lab I had promoted Cliff Lane to clinical director of NIAID, where he, in addition to his own research on the pathogenesis of HIV, would have the major responsibility for the clinical study and care of patients throughout the institute. I also recruited and trained a considerable number of talented young people who worked closely with me at the lab bench where we designed the experiments, collected and analyzed data, discussed future directions, and wrote up our results for publication in the scientific literature. One such project studied the accumulation and persistence of HIV in the lymphoid tissues of the body. This would turn out to be a major stumbling block in future attempts to eradicate HIV completely from the body and thus cure the patient.
The residual virus in the body is referred to as the reservoir. One of the big unknowns was whether this reservoir of virus was actively replicating and damaging the immune system early in the course of infection when patients were feeling relatively well. This was referred to as the clinically inactive stage of HIV disease. In fact, HIV disease was not inactive. In what is considered by many a groundbreaking study in how the disease of AIDS evolves undetected, Giuseppe “Gepi” Pantaleo and I demonstrated that HIV was actively replicating in lymphoid tissues such as lymph nodes even when patients showed no symptoms. In other words, the virus was stealthily eroding the body’s immune system unbeknownst to the patient and the physician. Gepi, who was from Bari, Italy, came to my lab in 1989 following a fellowship in Genoa under my close friend and long-term colleague Dr. Lorenzo Moretta, one of the top immunologists in Europe. Simultaneously, my colleague and old friend Ashley Haase from the University of Minnesota demonstrated similar findings in his group of patients. Ashley and I had been trainees together at NIAID under Shelly Wolff. We both published our findings in the same issue of the prestigious scientific journal Nature in 1993, which generated a considerable amount of attention in the scientific community. In 1995, two other groups, led by David Ho in New York and George Shaw in Birmingham, Alabama, working independently, demonstrated the extraordinary degree of replication and turnover of virus and its destructive effects on the body’s immune cells. This finding showed us that HIV was unique in its ability to persistently replicate over years from the earliest stages of disease to the point of advanced destruction of the immune system. This knowledge would prove to be even more important later when highly effective drugs that could completely suppress the virus became available. These and other studies served as evidence that it was essential to initiate therapy as early as possible.
The reservoir of HIV was one of the major stumbling blocks to the cure of HIV. In 1997, I recruited Dr. Tae-Wook Chun fresh out of his doctoral studies at Johns Hopkins Medical Center in Baltimore. During his many years in my lab, Tae-Wook studied the HIV reservoir and attempted to eliminate or suppress it. Our studies on HIV pathogenesis were done in parallel with our other studies on how the body’s immune system responds to HIV. I performed most of these latter studies with Dr. Susan Moir, whom I had recruited as a postdoctoral fellow immediately following the receipt of her Ph.D. degree in Canada. Susan and I probed the complexities of how HIV evades the body’s immune response, particularly the antibody response to the virus. These studies were relevant because the development of an effective vaccine depended on the production by the body of a protective antibody response against the virus.
The gratification I felt from contributing to these incremental but critical studies that fit another piece of knowledge into the puzzle of HIV/AIDS and brought us closer to meaningful solutions is exactly what I had hoped for when I decided to pursue a career as a physician-scientist instead of a physician in private practice. My lab’s contributions went well beyond the individual patient for whom we were caring. It is a very different but equally powerful feeling when a patient leaves a hospital free from disease as a result of our clinical skills.
I had three roles to play in the fight against HIV. First, I was director of a large government institution responsible for the overall conduct of research on all infectious diseases including HIV/AIDS. Second, I was a physician responsible for clinical research on and care of people with HIV. Third, I was chief of a research laboratory doing basic and clinical research on HIV. The combination was intense, exhausting, and exhilarating.