In 1981, several weeks after the Centers for Disease Control reported five cases of the disease that would become known as AIDS, the first patient with HIV checked into the NCI Metabolism Branch ward at the NIH Clinical Center, beginning NCI's 25-year involvement in the fight against AIDS. Dr. Robert Yarchoan, Chief of NCI's HIV and AIDS Malignancy Branch, discusses NCI's contributions to AIDS research.

What role did NCI play at the beginning of the AIDS epidemic?

NCI researchers were positioned to make substantial contributions, and a number of intramural investigators stepped up to the plate. AIDS was in part an epidemic of unusual tumors. Key expertise to study the disease also existed within NCI's intramural program. Dr. Robert Gallo's group had recently developed the technology to grow T cells and had just discovered the first human retrovirus, HTLV-1. Their codiscovery of HIV and development of the first blood test helped catalyze HIV research on campus.

The NCI intramural program had significant expertise in immunology, retrovirology, epidemiology, and nucleoside chemistry. We also had a substantial drug development effort and clinical trials methodology. Dr. Gene Shearer and others did excellent work unraveling the immune defects in AIDS patients, and NCI epidemiologists did important early work. Drs. Hiroaki Mitsuya, Sam Broder, and I, along with a number of other NCI scientists, codeveloped AZT (zidovudine) with Burroughs Wellcome Co., and then went on to develop ddI (didanosine) and ddC (zalcitabine) as the first AIDS drugs. Other NCI scientists made key discoveries of the molecular biology of HIV, its structural biology, and disease pathogenesis, and provided the extramural community with a wealth of reagents over 2 decades of research.

How has NCI's HIV/AIDS research evolved in recent years?

AIDS research at NCI has evolved as the field has matured. Effort has been concentrated in selected areas of expertise and NCI research is now focused in three broad areas: developing new antivirals to treat infected patients, trying to develop vaccines to prevent new infections, and developing better diagnosis and treatments for AIDS-related malignancies. This has been reflected in programmatic developments such as the creation of the Drug Resistance and AIDS Vaccine Programs, and the Vaccine and HIV and AIDS Malignancy branches. There is now increasing focus on AIDS-related malignancies and substantial cross-fertilization between AIDS and cancer research.

The development of effective antiretroviral therapy in the United States has made an incredible impact on AIDS and AIDS-related malignancies. Survival of AIDS patients has increased dramatically, and the year-by-year rate of AIDS malignancies has decreased here. However, this is not the case in the developing world. While our country has been successful at developing treatments to keep AIDS from being a lethal disease, the decade's increased population of AIDS survivors face a new challenge: As they age, their cumulative risk of developing AIDS-related malignancies also increases. There is evidence that cancer is now the most common cause of death in HIV-infected patients in countries where antiretroviral therapy is available. There is still much work to be done.

How has NCI's HIV/AIDS research better prepared the institute for other health challenges?

Accomplishments during the early days of the AIDS epidemic demonstrate that the intramural program - because of the excellence of our scientists, the critical mass, and our greater freedom to shift gears - has a relatively unique ability to "self deploy" and effectively address urgent public health needs. The development of faculties and working groups has helped create a means of networking and communication that didn't exist before and that, I believe, will facilitate future collaborative research if a similar crisis occurs.