Current status and challenges of antiretroviral research and therapy.

Twenty-five years after the discovery of the therapeutic activity of azidothymidine (AZT), the first antiretroviral drug used in the clinic, infection with the human immunodeficiency virus (HIV) has become, at least in the industrialized world, a manageable chronic disease with a significant improvement in life expectancy and quality. Nevertheless, the number of new infections worldwide continues to rise, particularly in women, and effective drug treatments have not yet reached the vast majority of infected individuals in resource-limited countries. The current status of antiretroviral therapy is therefore encouraging, but significant challenges remain. Although highly active antiretroviral therapy (HAART) provides durable control of virus replication in many patients, it is not devoid of unwanted secondary effects, some of which are now surfacing in aging populations under long-term treatment. The emergence of multidrug resistance and transmission of drug-resistant HIV strains limit the clinical efficacy of current therapy. Further simplification of treatment and identification of more effective drug combinations are needed to improve patient adherence, the most significant cause of treatment failure. Finding new drugs and novel drug targets may lead to redefining the goals of antiretroviral therapy, with an attempt to achieve the ultimate objective: the eradication of infection. Preclinical and clinical biomedical research, rational drug design and a close collaboration with regulatory agencies to set standards for the transition of new treatment concepts into the clinic will be the cornerstones of future progress. This special issue of Antiviral Research [85(1), 2010] highlights the principal milestones of antiretroviral research over 25 years of drug discovery and development and offers a comprehensive analysis by leading experts of the efforts being made to meet the challenges of effective control of HIV infection. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.