Study Confirms that Combination Treatment Using a Protease Inhibitor Can Delay HIV Disease Progression and Death

"The further, significant reduction in disease progression conferred by indinavir when
given as part of a three-drug combination illustrates the rapid progress that the field of HIV
therapeutics has made in the last two years and suggests that further benefits can be achieved
with regimens of ever-increasing potency," commented Scott Hammer, M.D., protocol chair of
ACTG 320.
Volunteers in the study had CD4+ T cell counts below 200 per cubic millimeter (mm3) Of
blood at study entry and had taken ZDV for at least three months, but had received less than
one week of 3TC and no protease inhibitors. The mean baseline CD4+ T cell count of the
participants was 86 cells/mm.3 They were randomized to receive either the combination of ZDV
(600 mg/day), 3TC (300 mg/day) and indinavir (2400 mg/day), or ZDV plus 3TC plus placebo.
Participants intolerant to ZDV could use stavudine (d4T), and those developing toxicities or
experiencing mild disease progression were allowed to change to other approved nucleoside
analogues. The majority of participants received ZDV and 3TC for the duration of the study.
A total of 1,156 HIV-infected volunteers participated in ACTG 320. Participants were'enrolled at 33 sites of the NIAID-supported AIDS Clinical Trials Group, and at seven sites of the
National Hemophilia Foundation. They were followed for a median of 38 weeks, with some
patients being followed for up to one year. Further studies are needed to understand the longterm impact of this triple combination. Sub-studies of ACTG 320 are currently being analyzed,
including a study of how the various treatments affect the amount of virus in patients' blood and
to characterize the development of drug resistance in the different treatment arms.
Survival and a delay in disease progression were significantly better in patients receiving
triple combination therapy. In that group, AIDS-defining illnesses, including opportunistic
infections and cancers, and deaths were decreased by approximately half. Sixty-three
instances of disease progression (including AIDS-defining illnesses and deaths) occurred in
volunteers on the ZDV/3TC arm versus 33 in volunteers on the triple combination arm.

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