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HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir–ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had Failed

Andrew R. Zolopa, MD; Robert W. Shafer, MD; Ann Warford, PhD; Jose G. Montoya, MD; Phillip Hsu, BA; David Katzenstein, MD; Thomas C. Merigan, MD; and Brad Efron, PhD
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From Stanford University School of Medicine, Stanford, California.


Acknowledgments: The authors thank Mitch Katz, MD, of the Department of Public Health, San Francisco, for critical review of the manuscript, and John Sninsky, PhD, of Roche Molecular Systems, Alameda, California, for contributing PCR kits and reagents used in the HIV-1 sequencing reactions.

Requests for Reprints: Andrew R. Zolopa, MD, Division of Infectious Diseases and Geographical Medicine, Stanford University School of Medicine, Grant Building, Room S-156, Stanford, CA 94305; e-mail, azolopa@stanford.edu.

Current Author Addresses: Drs. Zolopa, Shafer, Warford, Montoya, Hsu, Katzenstein, and Merigan: Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Grant Building Room S-156, Stanford, CA 94305.

Dr. Efron: Department of Statistics, Stanford University, Sequoia Hall, Room 132, Stanford CA 94305.


Ann Intern Med. 1999;131(11):813-821. doi:10.7326/0003-4819-131-11-199912070-00003
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Combination antiretroviral therapy for HIV-1 infection has resulted in profound control of HIV replication in vivo, improved immune function, and significant decreases in AIDS-related morbidity and mortality (19). For many persons, however, this therapy does not provide sustained viral suppression or durable clinical benefit (1011). Potential reasons for the loss of viral suppression include host immune defects, poor adherence to therapy, pharmacologic factors, and drug resistance (1017). However, HIV-1 resistance to drug therapy is probably the central factor in the loss of viral suppression (1822).

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Figures

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Figure 1.
Virologic response to saquinavir plus ritonavir through week 26 based on response by week 12.

See the Methods section for further explanation. Triangles represent nonresponders; diamonds represent partial responders; circles represent complete responders.

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Figure 2.
Frequencies of protease and reverse transcriptase mutations by virologic response at week 12.white barsstriped barssolid bars*P**P***P

Mutation frequencies at baseline in complete responders ( ), partial responders ( ), and nonresponders ( ) are shown. < 0.05; < 0.01; < 0.001 (as bivariate predictors).

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Summary for Patients

Drug Resistance Tests to Predict Response to Treatment for HIV Infection

The summary below is from the full report titled “HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir–ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had Failed.” It is in the 7 December 1999 issue of Annals of Internal Medicine (volume 131, pages 813-821). The authors are A.R. Zolopa, R.W. Shafer, A. Warford, J.G. Montoya, P. Hsu, D. Katzenstein, T.C. Merigan, and B. Efron.

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