Download ACTG 002: December 2, 1986, First Study, First Subject

ACTG 002: December 2 1986, First Study, First Subject
Twenty-five years ago, on December 2, 1986, the ACTG’s research site at the University of
Miami enrolled the network’s first subject to its first active clinical trial. The study was
ACTG 002. Its chair, Margaret Fischl MD was—and still is—Principal Investigator of the Miami
ACTU.
Dr. Fischl and her colleagues had already shown that a nucleoside analog reverse-transcriptase
inhibitor called AZT was an effective treatment for AIDS, albeit with serious side effects, and
wanted to establish that lower doses could provide similar survival benefits with diminished
adverse reactions. . Consequently, the team designed ACTG 002, A Multi-Center Clinical Trial
to Evaluate AZT in the Treatment of HIV Infection in Patients with AIDS post First Episode PCP.
The study was approved quickly—although it went through 11 versions on the way—and set the
standard for many protocols that followed it. Its classic rollover design was widely adopted in
clinical research, and the study set the pace for broadening eligibility criteria in the face of a
changing epidemic; the team recognized this need early and included pediatric participants
among their enrollees.
ACTG 002 is also an early example of the ACTG always doing more, such as the study’s use of
the CD4 T-cell count as a surrogate marker (which spurred a hot debate that lasted for years)
and its attention (in the pre-viral load era) to the reduction in virus coded products or
disappearance of culturable virus from the blood or blood fluids.
The study—the results of which were published on October 11, 1990 in the New England
Journal of Medicine—was a success, concluding that the lower dose used in ACTG 002 was at
least as effective as the previous, higher dose of zidovudine, and had fewer side effects.
Incidentally, the study did have one quirk: azidothymidine (AZT), the initial name for the study
drug, was actually the approved name of a different drug for an entirely different indication,
necessitating a new name upon FDA approval. Although the study drug for ACTG 002 is now
called zidovudine, the name AZT has stuck in the minds of most people. But, whatever the
names, ACTG 002 has made its mark on the HIV epidemic and on clinical research. The ACTG
has done great things since December 2, 1986—337 protocols concluded and almost 100,000
trial participants studied—and ACTG 002 blazed the way to develop effective treatment for HIV
infection. It was the first.