MAINTENANCE ANTIRETROVIRAL THERAPIES IN HIV-INFECTED SUBJECTS WITH UNDETECTABLE PLASMA HIV RNA AFTER TRIPLE-DRUG THERAPY

Background Combination antiretroviral therapy with indinavir, zidovudi ne, and lamivudine can suppress the level of human immunodeficiency vi rus (HIV) RNA in plasma below the threshold of detection for two years or more. We investigated whether a less intensive maintenance regimen could sustain viral suppression after an initial response to combinat ion therapy. Methods HIV-infected subjects who had CD4 cell counts gre ater than 200 per cubic millimeter, who had been treated with indinavi r, lamivudine, and zidovudine, and who had less than 200 copies of HIV RNA per milliliter of plasma after 16, 20, and 24 weeks of induction therapy were randomly assigned to receive either continued triple-drug therapy (106 subjects), indinavir alone (103 subjects), or a combinat ion of zidovudine and lamivudine (107 subjects). The primary end point was loss of viral suppression, which was defined as a plasma level of at least 200 copies of HIV RNA per milliliter on two consecutive meas urements during maintenance therapy. Results During maintenance treatm ent, 23 percent of the subjects receiving indinavir and 23 percent of those receiving zidovudine and lamivudine, but only 4 percent of those receiving all three drugs, had loss of viral suppression (P<0.001 for the comparison between triple-drug therapy and the other two maintena nce regimens). Subjects with greater increases in CD4 cell counts duri ng induction therapy, higher viral loads at base line (i.e., at the be ginning of induction therapy), and slower rates of viral clearance wer e at greater risk for loss of viral suppression. The presence of zidov udine-resistance mutations in HIV RNA at base line was strongly predic tive of the loss of viral suppression in subjects treated with zidovud ine and lamivudine. Conclusions The suppression of plasma HIV RNA afte r six months of treatment with indinavir, zidovudine, and lamivudine i s better sustained by the continuation of these three drugs than by ma intenance therapy with either indinavir alone or zidovudine and lamivu dine. (N Engl J Med 1998;339:1261-8.) (C)1998, Massachusetts Medical S ociety.