Efficacy and Tolerability of Stavudine plus Lamivudine in Treatment-Naive and Treatment-Experienced Patients with HIV-1 Infection

1 October 1998 | Volume 129 Issue 7 | Pages 525-531

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.

Author and Article Information

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.