A RANDOMIZED TRIAL OF 3 MAINTENANCE REGIMENS GIVEN AFTER 3 MONTHS OF INDUCTION THERAPY WITH ZIDOVUDINE, LAMIVUDINE, AND INDINAVIR IN PREVIOUSLY UNTREATED HIV-1-INFECTED PATIENTS

Background The long-term effectiveness of potent three-drug antiretrov iral regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection is limited by problems related to compliance and to lerability. We investigated whether two-drug maintenance therapy would suppress viral replication after a three-month period of aggressive t riple-drug induction therapy. Methods A total of 378 HIV-1-infected ad ults who had not received previous antiretroviral treatment received t hree months of induction therapy consisting of 300 mg of zidovudine ev ery 12 hours, 150 mg of lamivudine every 12 hours, and 800 mg of indin avir every 8 hours. The 279 patients in whom the plasma HIV-1 RNA tite r fell below 500 copies per milliliter after two months of triple-drug therapy, and who completed the induction phase, were randomly assigne d at month 3 to one of the following three open-label maintenance regi mens: zidovudine, lamivudine, and indinavir; zidovudine and lamivudine ; or zidovudine and indinavir. The primary end point was an increase i n HIV-1 RNA levels to 500 copies or more per milliliter during the mai ntenance phase. Results The proportion of patients who reached the pri mary end point was significantly higher among patients receiving zidov udine plus lamivudine (29 of 93 patients, P<0.001) or zidovudine plus indinavir (21 of 94, P=0.01) than among patients receiving continued t riple-drug therapy (8 of 92). This higher failure rate in the groups t reated with the two-drug maintenance regimens was also observed in the subgroup of patients with maximally suppressed HIV-1 RNA (below 50 co pies per milliliter) at the time of randomization to maintenance thera py. Conclusions In HIV-1-infected adults not previously treated with a ntiretroviral drugs whose plasma HIV-1 RNA levels fell below 500 copie s per milliliter after three months of induction therapy with zidovudi ne, lamivudine, and indinavir, two-drug maintenance therapy was less e ffective in sustaining a reduced viral load than continued three-drug therapy. (N Engl J Med 1998;339:1269-76.) (C)1998, Massachusetts Medic al Society.