Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients - A randomized controlled comparison with zidovudine monotherapy

Objective.-To compare safety and efficacy of lamivudine-zidovudine combination therapy with zidovudine monotherapy in treating human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral therapy-naive patients. Design.-Double-blind, randomized, multicenter, comparative trial of 129 patients throughout 24 weeks followed by 24 weeks of open-label lamivudine in combination with zidovudine. Setting.-Outpatients from 14 hospitals in Belgium, France, Germany, Spain, and the United Kingdom were enrolled within 6 months. Patients.-HIV-1-positive, antiretroviral-naive (less than or equal to 4 weeks prior zidovudine use) patients aged at least 18 years with CD4(+) cell counts between 0.10 x 10(9)/L and 0.40 x 10(9)/L (100-400/mu L). Intervention.-Patients received either 300 mg of lamivudine every 12 hours in combination with 200 mg of zidovudine every 8 hours for 24 weeks or zidovudine monotherapy for 24 weeks. All patients were then allowed to receive zidovudine in combination with open-label lamivudine (300 mg every 12 hours). Main Outcome Measures.-Efficacy was assessed by changes in CD4(+) cell counts, beta(2)-microglobulin, neopterin, HIV-1 immune-complex dissociated (ICD) p24 antigenemia, and HIV-1 viral load. Safety was assessed by incidence of adverse clinical events and defined laboratory-measured toxic effects. Results.-Combination therapy showed superior treatment effects compared with monotherapy during the first 24 weeks as documented by changes in CD4(+) cell counts (increase of 0.08 x 10(9)/L vs 0.02 x 10(9)/L, P<.001), ICD p24 (-88% vs -49%; P=.04), cellular viremia (-1.27 vs -0.20 log(10) median tissue-culture infected dose [TCID50] per 10(6) peripheral blood mononuclear cells; P=.001), and viral load measured by HIV-1 RNA polymerase chain reaction using a Roche method (-1.33 vs -0.57 log(10) copies/mL; P=.001) or an immune-capture method (-0.6 vs -0.14 log,, copies/mL; P=.008). Observed changes were sustained to 48 weeks for patients continuing to