Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults

Background: Efavirenz is a nonnucleoside reverse-transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). We compared two regimens cont aining efavirenz, one with a protease inhibitor and the other with two nucl eoside reverse-transcriptase inhibitors, with a standard three-drug regimen . Methods: The study subjects were 450 patients who had not previously been t reated with lamivudine or any nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. In this open-label study, patients were randomly as signed to one of three regimens: efavirenz (600 mg daily) plus zidovudine ( 300 mg twice daily) and lamivudine (150 mg twice daily); the protease inhib itor indinavir (800 mg every eight hours) plus zidovudine and lamivudine; o r efavirenz plus indinavir (1000 mg every eight hours). Results: Suppression of plasma HIV-1 RNA to undetectable levels was achieve d in more patients in the group given efavirenz plus nucleoside reverse-tra nscriptase inhibitors than in the group given indinavir plus nucleoside rev erse-transcriptase inhibitors (70 percent vs. 48 percent, P<0.001). The eff icacy of the regimen of efavirenz plus indinavir was similar (53 percent) t o that of the regimen of indinavir, zidovudine, and lamivudine. CD4 cell co unts increased significantly with all combinations (range of increases, 180 to 201 cells per cubic millimeter). More patients discontinued treatment b ecause of adverse events in the group given indinavir and two nucleoside re verse-transcriptase inhibitors than in the group given efavirenz and two nu cleoside reverse-transcriptase inhibitors (43 percent vs. 27 percent, P=0.0 05). Conclusions: As antiretroviral therapy in HIV-1-infected adults, the combin ation of efavirenz, zidovudine, and lamivudine has greater antiviral activi ty and is better tolerated than the combination of indinavir, zidovudine, a nd lamivudine. (N Engl J Med 1999;341:1865-73.) (C)1999, Massachusetts Medi cal Society.