Efficacy and tolerability of stavudine plus lamivudine in treatment-naive and treatment-experienced patients with HIV-1 infection

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/mm(3) (42 treatment-naive and 41 treatment-experienced patients). Interventions: Stavudine, 40 mg twice daily (30 mg twice daily in patients with a body weight less than or equal to 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 log(10) (10(1.66)) (range, -3.04 to -0.79 log(10)) in plasma HIV-1 RNA; the median increase in CD4(+) cell count was 108 cells/mm(3) (range, -58 to 406 cells/mm(3)) at week 24 in treatment-naive patients. In treatment-experienced patients, the median reduction in plasma HIV-1 RNA was 0.55 log(10) (range, -2.86 to 0.52 log(10)), and the median increase in CD4(+) cell count was 46 cells/mm(3) (range, -188 to 311 cells/mm(3)). 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.