Background: The new protease inhibitors are potent
inhibitors of the human immunodeficiency virus
(HIV), and in combination with other antiretroviral
drugs they may be able to cause profound and sustained
suppression of HIV replication.
Methods: In this double-blind study, 97 HIV-infected
patients who had received zidovudine treatment
for at least 6 months and had 50 to 400 CD4 cells per
cubic millimeter and at least 20,000 copies of HIV
RNA per milliliter were randomly assigned to one of
three treatments for up to 52 weeks: 800 mg of indinavir
every eight hours; 200 mg of zidovudine every
eight hours combined with 150 mg of lamivudine
twice daily; or all three drugs. The patients were followed
to monitor the occurrence of adverse events
and changes in viral load and CD4 cell counts.
Results: The decrease in HIV RNA over the first 24
weeks was greater in the three-drug group than in
the other groups (P�0.001 for each comparison).
RNA levels decreased to less than 500 copies per
milliliter at week 24 in 28 of 31 patients in the threedrug
group (90 percent), 12 of 28 patients in the indinavir
group (43 percent), and none of 30 patients
in the zidovudine–lamivudine group. The increase in
CD4 cell counts over the first 24 weeks was greater
in the two groups receiving indinavir than in the zidovudine–
lamivudine group (P<0.01 for each comparison).
The changes in the viral load and the CD4
cell count persisted for up to 52 weeks. All the regimens
were generally well tolerated.
Conclusions: In most HIV-infected patients with
prior antiretroviral therapy, the combination of indinavir,
zidovudine, and lamivudine reduces levels of
HIV RNA to less than 500 copies per milliliter for as
long as one year. (N Engl J Med 1997;337:734-9.