Efficacy and Tolerability of Stavudine plus Lamivudine in Treatment-Naive and Treatment-Experienced Patients with HIV-1 Infection
- Christine Katlama, MD;
- Marc-Antoine Valantin, MD;
- Sophie Matheron, MD;
- Anne Coutellier, MD;
- Vincent Calvez, MD;
- Diane Descamps, MD;
- Christophe Longuet, MD;
- Manuela Bonmarchand, MD;
- Roland Tubiana, MD;
- Marcio De Sa, MD;
- Remi Lancar, MSc;
- Henri Agut, MD;
- Francoise Brun-Vezinet, MD; and
- Dominique Costagliola, PhD
- From Hopital Pitie-Salpetriere, Hopital Bichat-Claude Bernard, and INSERM SC4, Institut Saint Antoine de Recherche en Sante, Paris, France. Grant Support: By Agence Nationale de Recherche sur le SIDA, Paris, France. Acknowledgments: The authors thank the study and manuscript staff members who contributed to the study; the participants; the technical assistant (M. Pauchard); the pharmacists (M.H. Fievet, PhD, and A. Certain, PhD); Bristol-Myers Squibb, Inc. (J.J Gres, MD, and P. Ngovan, MD), and Glaxo Wellcome (D. Lapierre, MD, and A. Fetter, MD), which contributed study medication; and J. Hawes for assistance in manuscript preparation. Requests for Reprints: Christine Katlama, MD, Department of Infectious Diseases, Hopital Pitie-Salpetriere, 47, Boulevard de l'Hopital, 75013 Paris, France. Current Author Addresses: Drs. Katlama, Valantin, Tubiana, De Sa, and Agut: Department of Infectious Diseases, Hopital Pitie-Salpetriere, 47, Boulevard de l'Hopital, 75013 Paris, France.
Abstract
Background: A combination of two nucleoside analogues is currently the core of any antiretroviral regimen for HIV-1 infection. Stavudine plus lamivudine has shown an additive effect in vitro, as well as an absence of overlapping toxicity and cross-resistance.
Objective: To evaluate the antiviral efficacy of stavudine plus lamivudine in treatment-naive patients and in patients previously treated with other nucleoside reverse transcriptase inhibitors.
Design: Prospective, open-label pilot study.
Setting: Three urban clinical centers in Paris.
Patients: 83 patients with CD4+ cell counts between 50 and 400 cells/mm3 (42 treatment-naive and 41 treatment-experienced patients).
Interventions: Stavudine, 40 mg twice daily (30 mg twice daily in patients with a body weight ≤ 60 kg), and lamivudine, 150 mg twice daily.
Measurements: Primary end points for efficacy included changes in plasma viral load and CD4+ cell count at 24 weeks compared with baseline.
Results: Therapy with stavudine plus lamivudine resulted in a median decrease of 1.66 log10 (101.66) (range, −3.04 to −0.79 log10) in plasma HIV-1 RNA; the median increase in CD4+ cell count was 108 cells/mm3 (range, −58 to 406 cells/mm3) at week 24 in treatment-naive patients. In treatment-experienced patients, the median reduction in plasma HIV-1 RNA was 0.55 log10 (range, −2.86 to 0.52 log10), and the median increase in CD4+ cell count was 46 cells/mm3 (range, −188 to 311 cells/mm3). The percentages of patients with less than 3000 HIV-1 RNA copies/mL and less than 400 copies/mL at 24 weeks were, respectively, 57% (95% CI, 41% to 72%) and 26% (CI, 12% to 40%) among treatment-naive patients and 22% (CI, 10% to 38%) and 5% (CI, 1% to 17%) among treatment-experienced patients. Of 82 patients, 14 (17%) experienced grade 3 or 4 toxicity and 2 discontinued therapy because of intolerance toward treatment.
Conclusion: Stavudine plus lamivudine seems to have a potent antiviral effect in treatment-naive and treatment-experienced patients. No major drug-limiting toxicity was found. This two-nucleoside combination should be considered in multidrug therapy for HIV.
- Copyright ©2004 by the American College of Physicians
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