A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less
Background: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to
treat human immunodeficiency virus type 1 (HIV-1)
infection are not clear. We compared treatment with
the protease inhibitor indinavir in addition to zidovudine
and lamivudine with treatment with the two nucleosides
alone in HIV-infected adults previously treated
with zidovudine.
Methods: A total of 1156 patients not previously
treated with lamivudine or protease inhibitors were
stratified according to CD4 cell count (50 or fewer vs.
51 to 200 cells per cubic millimeter) and randomly
assigned to one of two daily regimens: 600 mg of zidovudine
and 300 mg of lamivudine, or that regimen
with 2400 mg of indinavir. Stavudine could be substituted
for zidovudine. The primary end point was
the time to the development of the acquired immunodeficiency
syndrome (AIDS) or death.
Results: The proportion of patients whose disease
progressed to AIDS or death was lower with indinavir,
zidovudine (or stavudine), and lamivudine (6 percent)
than with zidovudine (or stavudine) and lamivudine
alone (11 percent; estimated hazard ratio,
0.50; 95 percent confidence interval, 0.33 to 0.76;
P�0.001). Mortality in the two groups was 1.4 percent
and 3.1 percent, respectively (estimated hazard
ratio, 0.43; 95 percent confidence interval, 0.19 to
0.99; P=0.04). The effects of treatment were similar
in both CD4 cell strata. The responses of CD4 cells
and plasma HIV-1 RNA paralleled the clinical results.
Conclusions: Treatment with indinavir, zidovudine,
and lamivudine as compared with zidovudine and
lamivudine alone significantly slows the progression
of HIV-1 disease in patients with 200 CD4 cells or
fewer per cubic millimeter and prior exposure to zidovudine.
(N Engl J Med 1997;337:725-33.
