AIDS Research at the NIH: A Critical Review

and 156 is studying the combination of azithromycin and pyrimethamine for acute therapy.
The ACTG has also refined chemotherapy regimens, sometimes including bone-marrow protecting colony
stimulating factors (CSFs), for AIDS-related malignancies (006, 013, 014, 057, 075, 090, 094, 096, 109,
110 for KS; 008, 074 for lymphomas).
New trials. Recent additions to the ACTG roster include several non-nucleoside reverse transcriptase
inhibitors (nevirapine, ACTG 164, 168, 208; L,669 - ACTG 184; U-87201E - ACTG 199); several novel
potential antiretrovirals (synthetic hypericin - ACTG 150; CD4-PE40 - ACTG 201); potential immune based
therapies (pentoxifylline, ACTG 160); HIV immunogens (rgpl60 and others, ACTG 205, 209, 214). 5 -fluorouracil (5-FU) will be studied for secondary prevention of cervical dysplasia in HIV-infected women
(ACTG 200). The angiogenesis inhibitor AGM-1470 will enter phase I for Kaposi's sarcoma (ACTG 215).
Dexamethasone will be tried as supportive therapy for cryptococcal meningitis (ACTG 202). Large
prophylaxis studies for MAI (196) and CMV (204) are planned, and a TB prophylaxis study (177) is
underway. Albendazole will be tried out in microsporidiosis (207), and letrazuril and humatin are being
studied for cryptosporidiosis (198 + 192). Finally, although it depends on the uncertain wisdom of Roche,
plans are being made to conduct phase V1/11 studies of the Roche protease inhibitor (Ro 31-8959, ACTG
212) and tat inhibitor (ACTG 213, Ro 24-7429).
Over the last two years, the ACTG has weathered significant changes, including plateauing and then
declining budget growth, the metastasis of the pediatric ACTG system at the expense of the adult one,
shifting of resources away to the CPCRA and the DATRI, the recompetition of the adult ACTUs, harsh
public criticism from Congress, activists and the pharmaceutical industry, radical shifts in the regulatory
climate, incorporation of community representatives into its committee structure, and major leadership
transitions in its executive committee and elsewhere. Several of these developments occurred in response
to the original activist critique. Many of the changes have been slow in coming, and many profound
changes remain to be made. Following the recompetition of the 35 adult ACTUs, six units were initially
defunded, while seven new adult and nine new pediatric units were added to the system, bringing the total
to 29 adult ACTUs and 25 pediatric ACTUs. Following an outcry from activists, Congressmen and
researchers, NIAID restored interim funding to six defunded adult units through the end of 1992; their
ultimate fate will be decided in the presumably calmer post-election climate.
Units competing for the current cycle of five-year cooperative agreements had to guarantee that they would
be able to fill 60-150 clinical trial slots annually, depending on the level at which they were funded and the
"intensity score" of the protocols they undertook. Funds were to be awarded under a complicated scheme
by which 75-90% of the funds are in "core" awards, with the remainder doled out sometime later as
"incentive" funds to well-performing sites. The point of the core/incentive system was to tie funding to
performance - a long-term activist goal. The problem was that, in order to fund as many sites as possible,
but given current budget rises of 2.7% (1991) and 11% (1992), NIAID had to slash many sites' budget
requests by up to half. The result is that sites will be hard pressed to meet their "quotas." Many will opt
to do large outpatient trials rather than resource intensive oncology, neurology, OI treatment or advanced
AIDS trials. Recompeting sites had to guarantee that they would participate in trials of antiretroviral drugs
and of OI treatment and prophylaxis. Participation in oncology, neurology and immunology was entirely
optional, however. Supplemental funds were available for "developmental virology," and were awarded to
15 sites to continue developing virological assays. Twelve pharmacologists are funded by the ACTG, along
with a new central pharmacology lab. Immunology failed to do as well, with only five "advanced
immunology awards" being made, of under $100,000 each (barely enough for a technician, supplies, and
50% indirect costs). No funds were set aside for neurology. In order to deal with the budget cuts, many
sites had to lay off productive staff of considerable experience and dedication. Some sites are now
dependent for their true "core" funds upon their NCRR-funded MO1 General Clinical Research Center
(GCRC) awards, rather than upon their ACTG awards. Adult ACTUs have too many patients clamoring

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