AIDS Research at the NIH: A Critical Review

for too few trials, while pediatric ones have the opposite situation - too few patients for so many trials.
ACT UP members first attended the 7th ACTG in November 1989. What they found there led directly to
a campaign to open up the ACTG and restructure it; this campaign culminated in ACT UP's 'Storm the
NIH" demonstration on May 21, 1990. Following the demonstration, the ACTG meetings were opened to
all interested observers, activists and journalists. In November 1990, at the 10th ACTG, members of the
Community Constituency Group (CCG), a 24-member committee including activists, people with HIV,
women, African Americans, Latinos, HIV-infected mothers and mothers of HIV-infected children, people
living with hemophilia and ex-injection drug users, became voting members of all ACTG research and
resource committees, including the Executive Committee. The CCG and other persistent activists have
begun to effect some slow but profound changes in the ACTG. Some researchers, especially in Ols,
immunology and neurology, have proved eager to work with activists and open to new ideas.
While ACTG leaders have professed a commitment to increasing the study of immune-based therapies,
including cytoldkine inhibitors and HIV immunogens, DAIDS has provided no resources to scale up the
necessary immunologic assays (delayed type hypersensitivity, cytotoxic T lymphocytes, proliferative
responses, neutralizing antibodies, cytokine or HIV mRNA levels, etc.).
The ACTG's Primary Infection Committee remains refractory, insular, uncommunicative and deliberately
uncognizant of resource limitations and logistical obstacles. Community activists have never been happy
with the recent series of large, last-gasp nucleoside trials (076 in pregnant women, 175 in asymptomatics,
193 in people with under 50 CD4 cells). Pervasive problems with these large, expensive studies are
seldom addressed until after the fact, when much damage has been done. For example, women from 076
who have given birth are not followed up formally. There is no follow-up study for them to enroll in. The
baby remains on trial drug, while the mother is dropped. The CCG and the ACTG Data + Safety Monitoring
Board have asked for provision to be made for these women for over one year without result. Meanwhile,
in ACTG 175, people are choking, vomiting and dropping off study because of the enormous and
unpalatable ddl pills used therein. ACTG 193 will subject its participants - people with CD4<50 - to 20-40
pills a day (including up to 2/3 placebos) in a double-blind comparison of alternating vs. combination
AZT/ddl and AZT/ddC. This population will also be asked to join two placebo-controlled double-blind
studies for MAI and CMV prophylaxis, ACTG 196 and 204. 193 may well crash, since its drugs can be
obtained commercially, unlike the study drugs of the more important and more novel OI prophylaxis studies.
There is still no system to streamline ACTG data validation, analysis and publication. Many of the ACTG's
most important completed studies - especially OI studies - remain unpublished. Vital contributions to the
standard of care thus remain unremarked in the medical literature, and unavailable to most people with HIV
and their primary care physicians. Because of problems like these with timely data analysis and other
problems of turf, control and paranoia, many pharmaceutical companies have become unwilling to work
with the ACTG. Some, such as Roche, do their phase I studies abroad. Others, like Abbott, have
withdrawn from collaboration with NIAID even though NIH funds paid for discovery of Abbott's protease
inhibitor. In the absence of unanimous pharmaceutical acclaim and the continuing dearth of agents ready
for large-scale evaluation, the ACTG could switch its attention to small pathogenesis-directed trials, but has
not yet done so. Even if the tat or protease inhibitors were to demonstrate potential activity, the ACTG at
its present size and shape cannot afford to take more than one drug through "critical path" studies to
licensure at a time. The experience with ddl and ddC (where the phase II studies of the latter were
conducted mainly outside the ACTG) shows that the system cannot accommodate more than one NDA
program at a time.
Community Programs for ClInical Research on AIDS (CPCRA). The CPCRA was set up with $9M in
FY 1990 (funding started in fall 1989) and grew by 92% to $17.2M in FY 1991. It is projected to cost about
$19M in FY 1993. The CPCRA's 18 sites include many hospitals and clinics which serve populations

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