Infection with HIV-1 leading to AIDS has been the greatest biomedical challenge of this century. In December 1997 the World Health Organisation estimated that 11.7 million people had died, more than 30 million were still infected, and 16 000 new infections were occurring each day. Of the 30 million people infected, 27 million are thought to be unaware of their infection. The disease has been especially devastating because of its concentration in young adults, which affects social stability from the level of individual families to national economies.

Improved understanding of HIV-1 biology and its treatment have set the stage for a variety of new scientific initiatives to combat the epidemic.1^–8 New drug combinations that include protease inhibitors have led to prolonged survival, and a better definition of HIV-1 pathogenesis. Highly active antiretroviral therapy has provided hope that AIDS may one day be conquered, but its high cost has raised new issues, particularly that of equity, with the burden of the epidemic shifting into poorer populations. Scientists, healthcare workers, public health officials, and politicians need to acknowledge that the epidemic is a global problem and that mechanisms for combatting the disease should supersede nationalistic interests.

This article explores three fundamental aspects of HIV-1 biology that will be the focus of intensive research over the next few years and, ultimately, have direct bearing on clinical practice and public health approaches to HIV infection.