Special Communication
February 14, 2001

Virologic and Regimen Termination Surrogate End Points in AIDS Clinical Trials

Author Affiliations

Author Affiliations: Department of Biostatistics, Harvard School of Public Health, Boston, Mass (Drs Gilbert and DeGruttola); Division of Infectious Diseases, Columbia Presbyterian Center, New York, NY (Dr Hammer); and University of Colorado Health Sciences Center, Denver (Dr Kuritzkes).

JAMA. 2001;285(6):777-784. doi:10.1001/jama.285.6.777

Suppression of plasma human immunodeficiency virus (HIV) RNA levels has been widely accepted as an appropriate surrogate end point for HIV disease progression, and it is currently used as the primary end point to determine efficacy in many antiretroviral trials. However, this end point does not always measure other important effects of treatment, such as inducement of multidrug resistance, which depletes future therapy options, and toxic effects. An alternative that directly factors in these treatment costs is a composite regimen termination end point, defined as a protocol-determined change in regimen due to either virologic failure or treatment-related toxic effects. Pros and cons for using purely virologic vs various composite primary end points are discussed. Conclusions include (1) a trial's clinical objective guides the choice of primary end point, (2) a purely virologic end point is often preferable, (3) it may be important to analyze both end point types in interpreting study results, and (4) long-term clinical outcome studies are needed for identifying the most predictive surrogate end points.