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.


METHODS
Prospective, open-label pilot study.


METHODS
Three urban clinical centers in Paris.


METHODS
83 patients with CD4+ cell counts between 50 and 400 cells/mm3 (42 treatment-naive and 41 treatment-experienced patients).


METHODS
Stavudine, 40 mg twice daily (30 mg twice daily in patients with a body weight < or = 60 kg), and lamivudine, 150 mg twice daily.


METHODS
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 (10(1.66)) (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.


CONCLUSIONS
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.
Hôpital Pitié-Salpêtrière, and INSERM SC4, Institut Saint Antoine de Recherche en Santé, Paris, France.
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D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018119:Stavudine / Q000009:adverse effects* / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D018119:Stavudine