A 'second life' agenda. Psychiatric research issues raised by protease inhibitor treatments for people with the human immunodeficiency virus or the acquired immunodeficiency syndrome.

Seldom in the history of medicine has an entire generation of patients with an incurable, progressive, and ultimately fatal disease suddenly been offered the prospect of extended survival and even, perhaps, a "second life." The relatively simultaneous appearance of 2 major treatment developments has created profound changes in therapeutic options and outlook. The first development is an assay of serum levels of human immunodeficiency virus viral copies, providing a critical tool for clinical decision making. The second is the marketing between December 1995 and April 1997 of 4 human immunodeficiency virus protease inhibitors that, combined with previously available antiviral medications, achieve a new level of efficacy. With the advent of these changes come multiple psychiatric research and policy issues. These include the development of strategies to establish and maintain medication adherence. This is a critical task, given the complexity of combination therapy regimens and the rapid onset of viral resistance to protease inhibitors within days to weeks of missed or suboptimal dosing. The psychological issues to be studied include the process of restructuring lives and expectations in the event of clinical benefit or managing the distress associated with clinical failure. Other research questions include the effects of restored health on the appraisal of human immunodeficiency virus risk behaviors, assessment of effect of neurocognitive functioning, and unanswered questions about psychotropic or protease inhibitor drug interactions due to their shared metabolic pathways. Behavioral scientists can inform provision of care to patients who may be considered difficult to treat, such as those with severe and persistent mental illness or active substance abuse or the homeless. This includes the provision of empirical data regarding individual and situational characteristics that are likely to promote or impede adherence, as well as innovative provision systems. Psychiatry can make notable contributions during this turning point in human immunodeficiency virus therapeutics and research.