SAFETY AND EFFICACY OF LAMIVUDINE-ZIDOVUDINE COMBINATION THERAPY IN ZIDOVUDINE-EXPERIENCED PATIENTS - A RANDOMIZED CONTROLLED COMPARISON WITH ZIDOVUDINE MONOTHERAPY

Objective.-To compare the safety and efficacy of 2 doses of lamivudine given in combination with zidovudine with continued zidovudine monoth erapy. Design.-Double-blind, randomized, multicenter, comparative tria l of 223 patients treated for 24 weeks. Setting.-Patients from 32 hosp itals in Europe were enrolled th roughout a 1-year period. Patients.-A dult human immunodeficiency virus type 1 (HIV-1)-positive, zidovudine- experienced (greater than or equal to 24 weeks prior zidovudine) patie nts with CD4(+) cell counts between 0.10 and 0.40x10(9)/L (100-400 cel ls/mu L). Intervention.-Patients received either 200 mg of zidovudine every 8 hours, 150 mg of lamivudine every 12 hours plus zidovudine, or 300 mg of lamivudine every 12 hours plus zidovudine for 24 weeks. All patients were then allowed to receive zidovudine and open-label lamiv udine combination therapy. Twelve patients withdrew because of adverse events during the 24-week treatment period. Main Outcome Measures.-Ef ficacy was measured by evaluating immunological and viral load changes , and safety was assessed by evaluating clinical manifestations and la boratory indexes of toxic effects. Results.-Patients receiving low- or high-dose combination therapy had greater treatment effects compared with patients receiving continued zidovudine monotherapy during the fi rst 24 weeks as documented by changes in CD4(+) cell counts (+0.04 vs +0.03 vs -0.02x10(9)/L, respectively; P<.001); log,, HIV-I RNA as meas ured by the Roche assay (-0.96 vs -0.77 vs +0.07 copies/mL, respective ly; P<.001) or log(10) HIV-1 RNA measured by the quantitative nucleic acid sequence-based amplification assay (-0.59 vs -1.06 vs -0.02 copie s/mL, respectively; P<.011); and immune-complex dissociated (ICD) p24 antigen (-74% vs -68% vs +27%, respectively; P<.001). There were no st atistically significant differences in viral measurements, in CD4(+) c ell counts, or in safety profile between the groups receiving 2 doses of lamivudine in combination with zidovudine. The effects on CD4(+) ce ll counts and ICD p24 antigen were sustained throughout 48 weeks for p atients continuing combination therapy. Patients switching to combinat ion therapy at week 24 showed improvement. Conclusions.-In zidovudine- experienced HIV-1-infected patients, combination treatment with lamivu dine and zidovudine is well tolerated and provides greate; and more su stained increases in CD4(+) cell counts and decreases in viral load th an continued zidovudine monotherapy.