LAMIVUDINE PLUS ZIDOVUDINE COMPARED WITH ZALCITABINE PLUS ZIDOVUDINE IN PATIENTS WITH HIV-INFECTION

Objective: To compare the safety and activity of lamivudine plus zidov udine with the safety and activity of zalcitabine plus zidovudine in p atients with moderately advanced human immunodeficiency virus (HIV) in fection who had received zidovudine. Design: A multicenter, randomized , double-blind, three-arm, 24-week study with a blinded extension thro ugh at least 52 weeks. Setting: 21 sites in the United States, Canada, and Puerto Rico. Patients: 254 patients who had received zidovudine ( median duration of previous therapy, 20 months) and had absolute CD4() cell counts of 100 to 300 cells/mm(3). Interventions: Patients were randomly assigned to receive one of three regimens: 150 mg of lamivudi ne twice daily plus 200 mg of zidovudine three times daily (low-dose l amivudine group); 300 mg of lamivudine twice daily plus 200 mg of zido vudine three times daily (high-dose lamivudine group); or 0.75 mg of z alcitabine plus 200 mg of zidovudine three times daily (zalcitabine gr oup). Measurements: Immunologic activity was assessed primarily by cha nges in absolute CD4(+) cell counts; virologic activity was assessed b y changes in plasma HIV RNA levels as measured by reverse transcriptas e polymerase chain reaction. Safety of the treatment regimens was asse ssed through the reporting of adverse events. Results: 78% of patients completed 24 weeks of study treatment, and 63% of patients completed 52 weeks of study treatment. Changes in absolute CD4(+) cell counts we re significantly better for the low-dose and the high-dose lamivudine groups than for the zalcitabine group (median changes at 52 weeks were +42.5 cells/mm(3) in the low-dose lamivudine group, +23.33 cells/mm(3 ) in the high-dose lamivudine group, and -29.58 cells/mm(3) in the zal citabine group). Suppression of plasma HIV RNA levels was similar for all groups (median changes at 52 weeks were -0.48 log(10) copies/mL in the low-dose lamivudine group, -0.51 log(10) copies/mL in the high-do se lamivudine group, and -0.39 log(10) copies/mL in the zalcitabine gr oup). No significant differences in safety were seen among the three r egimens, although the low-dose lamivudine regimen appeared to be bette r tolerated than the others. Conclusions: In patients with HIV infecti on who had previously received zidovudine, 150 mg of lamivudine plus z idovudine resulted in greater immunologic evidence of benefit than did 0.75 mg of zalcitabine plus zidovudine and was better tolerated than 300 mg of lamivudine plus zidovudine.