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Abstract
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.