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January 12, 2000

Resistance, Fitness, Adherence, and Potency: Mapping the Paths to Virologic Failure

Author Affiliations

Author Affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY.

JAMA. 2000;283(2):250-251. doi:10.1001/jama.283.2.250

A near-uniformly fatal clinical syndrome, acquired immunodeficiency syndrome (AIDS), has been transformed during the past 5 years into a treatable infectious disease. The availability of potent antiretroviral agents coincided with the ability to measure levels of circulating virus in vivo. When used in tandem, an understanding of human immunodeficiency virus (HIV) replication dynamics in vivo was made possible, forming the scientific basis for the use of combination antiretroviral therapy.1 However, the treatment of HIV infection remains far from perfect, and new issues arise with regularity. Critical to achieving optimal therapeutic outcomes is an understanding of treatment failure. Early clinical trials of protease inhibitor monotherapy suggested that the pathway to treatment failure was exclusively via drug resistance.2,3 Viral rebound was thought to reflect failure of all components of a regimen. Furthermore, it was assumed that the absence of resistance-conferring genotypic changes reflected patient nonadherence.