AIDS Research at the NIH: A Critical Review

BASIC RESEARCH + DEVELOPMENT PROGRAM (BRDP) consists of the Pathogenesis, Developmental
Therapeutics, Vaccine Research + Development, and Resources + Centers Branches (PB, DTB, VRDB,
RCB respectively). Peggy Johnston, PhD, is Associate Director of the BRDP.
Pathogenesis Branch The chief of the Pathogenesis Branch (PB) is Gregory Milman. The PB pilots,
standardizes, stockpiles and supplies AIDS-related research supplies and reagents to the international
research effort, developing reference HIV isolates and proteins, susceptible cell lines, neutralizing
monoclonal antibodies, and other materials for basic research. Rather than focussing on the unresolved
issues of AIDS pathogenesis, the PB principally supports technologically-driven work, especially molecular
virology. For example, it helps to support the NIAID HIV Sequence Database + Analysis Unit in Los
Alamos; it contracts out to investigators who are cloning and sequencing HIV, SIV, FIV and other
retroviruses, and others making monoclonal and polyclonal antibodies. Its activities appear to be rather
technology-driven, rather than idea-driven. What does the PB conduct to bring together diverse
researchers, to catalyze collaboration, and maximize new research opportunities?
Developmental Therapeutics Branch (DTB) The acting chief of the Developmental Therapeutics Branch
(DTB) is Chuck Litterst, PhD. In fall 1991, he confessed his delight that activists were finally beginning to
pay attention to pre-clinical research. "We felt neglected before," he said. In FY 1991 DTB administered
$54,766,000 in extramural awards. Half of the awards funded solicited contracts and cooperative
agreements, including the National Cooperative Drug Discovery Groups for HIV and for AIDS-Related
Opportunistic Infections (NCDDG-HIV and NCDDG-OI, respectively). The other half funded investigatorinitiated basic therapeutic research. DTB support accounts for one quarter of the NIH's overall spending
on drug discovery and pre-clinical development, which totalled $144M in FY 1991.
National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV) The
first NCDDG awards were funded in fall 1986 and expired in August 1991. Several new rounds are still
active. As many as 22 NCDDG-HIV contracts (U01) have been funded, with 10 projected to be funded
through 1993-95. The NCDDG-HIV spent $14.3M in FY 1991 and is budgeted at $11.5M for FY 1992.
Four NCDDG-HIV awards were made in 1991. NCDDG-HIV researchers elucidated the three-dimensional
crystal structure of the CD4 molecule. Drugs whose anti-HIV activity was found by NCDDG contractors
include the Roche tat inhibitor, the Abbott protease inhibitor, the nucleosides d4T, AZdU, FLT and 3TC,
and the tumor necrosis factor (TNF) inhibitor pentoxifylline (Trental). NCDDG grantees include drug
companies and academics. The NCDDG underwrote the discovery of the anti-HIV activity of the Roche
tat gene inhibitors Ro 5-3335 (the lead compound) and Ro 24-7429 (the compound for clinical
development). In FY 1991 alone, Roche received $773,439 to develop inhibitors of tat and rev. Abbott's
protease inhibitor A-77003 was also developed with NCDDG-HIV funds. The Abbott NCDDG received
$666,881 to study integrase and protease in FY 1991. Apparently, Abbott has since decided to develop
its protease drug outside the NIH system, and has declined to accept further NCDDG funds.
NCDDG-OI Against a background of criticism from activists and from Congress that NIAID was ignoring
the opportunistic infections, in 1990 DTB solicited a series of NCDDG awards specifically for Ols. NCDDG01 awards totalled $5.7M in FY 1991 and will rise to $9.1M in FY 1992. Of the 11 NCDDG-OI awards
funded in 1991, four were for antifungals, three for Toxoplasma qondii, and one each for Mycobacterium
avium. Crvtosporidia. Pneumocystis, and CMV. Some of NIAID's anti-OI work is funded by DMID rather
than by DAIDS. DMID funds the Cooperative Antiviral Study Group (CASG), the Mycoses Study Group
(MSG), and preclinical herpesviruses (HSV, VZV, EBV, CMV), while DAIDS/DTB funds non-viral Ols.
Better in vitro and animal models are critical to further progress against Ols.
DTB Contracts DTB administers contracts supporting research on animal models for anti-HIV, anti-OI,
CNS-targeted and immune based therapies. DTB oversees confirmatory tests on the anti-HIV activity of
compounds processed through the NCI screening program, using altemative strains, cell lines and syncytia
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