3-Year Suppression of HIV Viremia with Indinavir, Zidovudine, and Lamivudine

  1. Roy M. Gulick, MD, MPH;
  2. John W. Mellors, MD;
  3. Diane Havlir, MD;
  4. Joseph J. Eron, MD;
  5. Anne Meibohm, PhD;
  6. Jon H. Condra, PhD;
  7. Fred T. Valentine, MD;
  8. Deborah McMahon, MD;
  9. Charles Gonzalez, MD;
  10. Leslie Jonas, BS;
  11. Emilio A. Emini, PhD;
  12. Jeffrey A. Chodakewitz, MD;
  13. Robin Isaacs, MD; and
  14. Douglas D. Richman, MD
  1. From Weill Medical College of Cornell University and New York University School of Medicine, New York, New York; University of Pittsburgh School of Medicine and Pittsburgh Veterans Affairs Medical Center, Pittsburgh, Pennsylvania; University of California and San Diego Veterans Affairs Medical Center, San Diego, California; University of North Carolina School of Medicine, Chapel Hill, North Carolina; and Merck Research Laboratories, West Point, Pennsylvania.

    Abstract

    Background: Antiretroviral regimens containing HIV protease inhibitors suppress viremia in HIV-infected patients, but the durability of this effect is not known.

    Objective: To describe the 3-year follow-up of patients randomly assigned to receive indinavir, zidovudine, and lamivudine in an ongoing clinical trial.

    Design: Open-label extension of a randomized, double-blind study.

    Setting: Four clinical research units.

    Patients: 33 HIV-infected, zidovudine-experienced patients with serum HIV RNA levels of at least 20 000 copies/mL and CD4 counts ranging from 50 to 400 cells/mm3.

    Intervention: Indinavir, zidovudine, and lamivudine.

    Measurements: Safety assessments, HIV RNA levels, CD4 cell counts, and genotypic analyses.

    Results: After 3 years of follow-up, 21 of 31 contributing patients (68% [95% CI, 49% to 83%]) had serum viral load levels less than 500 copies/mL. Twenty of 31 (65% [CI, 45% to 80%]) had levels less than 50 copies/mL. The median increase in CD4 count from baseline was 230 cells/mm3 (interquartile range, 150 to 316 cells/mm3). Nephrolithiasis occurred in 12 of 33 patients (36%).

    Conclusion: A three-drug regimen of indinavir, zidovudine, and lamivudine suppressed viremia in two thirds of patients for at least 3 years.

    Article and Author Information

    • Presented in part at the Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, Illinois, 31 January to 4 February 1999.

    • Disclaimer: Merck & Co., Inc., has made research grants to Cornell University; University of North Carolina; University of California, San Diego; and New York University. Drs. Gulick, Eron, and Richman are ad hoc consultants for Merck. Dr. Eron is an ad hoc consultant for Glaxo Wellcome. Drs. Gulick and Eron have received honoraria for lectures from Merck and Glaxo Wellcome. Drs. Meibohm, Condra, Emini, Chodakewitz, and Isaacs and Ms. Jonas are employees of Merck and own stocks and stock options.

    • Acknowledgments: The authors thank the patient volunteers and the study coordinators: Candida Talabucon, RN; Richard Hutt, RN; Nancy Mantz, BSN; Carl Garrubba, PA; Kathy Nuffer, RN; Jackie Stewart, RN; and Janet Kozel, PA. They thank Malathi Shivaprakash, MS; Kalpana Bakshi, MS; Robert M. Danovich, PhD; and Donald J. Graham, BS, for technical virologic support and Glaxo Wellcome for providing zidovudine and lamivudine.

    • Grant Support: By the National Institutes of Health (AI 36214 [University of California, San Diego, Center for AIDS Research] and P30-HD37260 [University of North Carolina Center for AIDS Research]) and by individual grants from Merck Research Laboratories, West Point, Pennsylvania.

    • Requests for Single Reprints: Roy M. Gulick, MD, MPH, Cornell Clinical Trials Unit, 525 East 68th Street, Box 566, New York, NY 10021; e-mail, rgulick{at}med.cornell.edu.

    • Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

    • Current Author Addresses: Dr. Gulick: Cornell Clinical Trials Unit, 525 East 68th Street, Box 566, New York, NY 10021.

    • Drs. Mellors and McMahon: Graduate School of Public Health, University of Public Health, University of Pittsburgh Medical Center, 603 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261.

    • Dr. Havlir: HIV Investigational Drug Treatment Center, University of California, San Diego, 2760 Fifth Avenue, Suite 300, San Diego, CA 92103.

    • Dr. Eron: Division of Infectious Diseases, University of North Carolina at Chapel Hill, 547 Burnett-Womack Building, CB 7030, Chapel Hill, NC 27599.

    • Drs. Meibohm, Condra, Emini, Chodakewitz, and Isaacs and Ms. Jonas: Merck & Co., Inc., Box 4, BL 3-4, West Point, PA 19486.

    • Drs. Valentine and Gonzalez: New York University School of Medicine, 550 First Avenue, CD 517, New York, NY 10016.

    • Dr. Richman: Departments of Pathology and Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093.

    • Author Contributions: Conception and design: R.M. Gulick, J.W. Mellors, D. Havlir, J.J. Eron, A. Meibohm, L. Jonas, E.A. Emini, J.A. Chodakewitz, R. Isaacs, D.D. Richman.

    • Analysis and interpretation of the data: R.M. Gulick, J.W. Mellors, D. Havlir, A. Meibohm, J.H. Condra, C. Gonzalez, E.A. Emini, R. Isaacs, D.D. Richman.

    • Drafting of the article: R.M. Gulick, J.W. Mellors, J.J. Eron, A. Meibohm, J.H. Condra, C. Gonzalez, R. Isaacs, D.D. Richman.

    • Critical revision of the article for important intellectual content: R.M. Gulick, J.W. Mellors, J.J. Eron, A. Meibohm, J.H. Condra, F.T. Valentine, D. McMahon, C. Gonzalez, J.A. Chodakewitz, R. Isaacs, D.D. Richman.

    • Final approval of the article: R.M. Gulick, J.W. Mellors, D. Havlir, J.J. Eron, A. Meibohm, J.H. Condra, F.T. Valentine, D. McMahon, E.A. Emini, J.A. Chodakewitz, R. Isaacs, D.D. Richman.

    • Provision of study materials or patients: R.M. Gulick, J.W. Mellors, D. Havlir, J.J. Eron, F.T. Valentine, D. McMahon, C. Gonzalez, L. Jonas, D.D. Richman.

    • Statistical expertise: A. Meibohm.

    • Administrative, technical, or logistic support: L. Jonas, R. Isaacs.

    • Collection and assembly of data: R.M. Gulick, J.W. Mellors, D. Havlir, J.H. Condra, C. Gonzales, L. Jonas, R. Isaacs.

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    1. Ann Intern Med July 4, 2000 vol. 133 no. 1 35-39
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