SIMULTANEOUS VS SEQUENTIAL INITIATION OF THERAPY WITH INDINAVIR, ZIDOVUDINE, AND LAMIVUDINE FOR HIV-1 INFECTION - 100-WEEK FOLLOW-UP

Context.-Combination antiretroviral therapy can markedly suppress huma n immunodeficiency virus (HIV) replication but the duration of HIV sup pression varies among patients. Objective.-To compare the antiretrovir al effect of a 3-drug regimen started simultaneously or sequentially i n patients with HIV infection, Design.-A multicenter, randomized, doub le-blind study, modified after at least 24 weeks of blinded therapy to provide open-label 3-drug therapy with follow-up through 100 weeks. S etting.-Four clinical research units Patients.-Ninety-seven patients w ith HIV infection who had taken zidovudine for at least 6 months with serum HIV RNA level of at least 20 000 copies/mL and CD4 cell count of 0.05 to 0.40 x 10(9)/L, Interventions.-Patients were initially random ized to receive 1 of 3 antiretroviral regimens: indinavir, 800 mg ever y 8 hours; zidovudine, 200 mg every 8 hours and lamivudine, 150 mg eve ry 12 hours; or all 3 drugs. After at least 24 weeks of blinded therap y, all patients received open-label 3-drug therapy. Main Outcome Measu res.-Anti retroviral activity was assessed by changes in HIV RNA level and CD4 cell count from baseline. Data through 100 weeks were summari zed. Results.-Simultaneous initiation of indinavir, zidovudine, and la mivudine suppressed HIV RNA in 78% (25/32) of contributing patients to less than 500 copies/ mi and increased CD4 cell count to a median of 0.209 x 10(9)/L above baseline at 100 weeks. When these 3 drugs were i nitiated sequentially, only 30% to 45% of contributing patients (10 of 33 in the zidovudine-lamivudine group and 13 of 29 in the indinavir g roup, respectively) had a sustained reduction in H(V RNA to less than 500 copies/mL, and median CD4 cell count increased to 0.101 to 0.163 x 10(9)/L above baseline at 100 weeks. Conclusions.-A 3-drug combinatio n of indinavir, zidovudine, and lamivudine, started simultaneously has durable antiretroviral activity for at least 2 years. Sequential init iation of the same 3 drugs is much less effective.