ACTG Highlights

Preclinical Of

Like the NCDDG-AIDS groups, each NCDDG-OI will be assembled by a principal
investigator. The principal investigator is responsible for forming a multidisciplinary
consortium representing the various skills needed to design, synthesize, and evaluate, at the
preclinical level, potential therapies for HIV-associated Ols. Consortium members may be
associated with academic, nonprofit, or commercial research organizations. A scientific
coordinator from NIAID will be affiliated with each NCDDG-OI.
Basic Research Grants
Several important accomplishments have resulted from ongoing basic research
projects supported by DTB. Investigators have:
* Developed novel methods for the efficient delivery of drugs to organs affected
by Ols. These include inhalation therapy for Pneumocystis carinii pneumonia
(PCP) and the development of liposomal-encapsulated amikacin, an antibiotic, for
Mycobacterium avium infections.
* Identified new classes of anti-OL agents that are produced naturally in the body.
Proteins named defensins, produced by scavenging white blood cells, have been
found to possess antifungal activity in vitro, and natural salivary proteins called
histatins have been discovered to have anti-Candida activity.
* Identified immunomodulators important in protecting against human
toxoplasmosis.
* Identified bovine colostrum (the first postpartum milk from lactating cows)
containing antibodies against Cryptosporidium as a potential protective therapy
for this infection.
* Conducted basic research on the life cycle of Pneumocystis carinii. This
information is useful for understanding how Pneumocystis carinii multiplies so
rapidly within the body.
* Identified a novel anti-Pneumocystis compound now under development by a
major pharmaceutical manufacturer.
Fifteen investigator-initiated (R01) grants for research on opportunistic infections
were funded in Fiscal Year 1989. Another seven grants are expected to be funded by the
summer of 1990.
Drug Screening and Animal Model Contracts
DAIDS is presently funding nine contracts for in vitro screening of potential
therapies for non-viral Ols. Eight of these contracts, under the direction of Barbara
Laughon, Ph.D., and Mohamed Nasr, Ph.D., include evaluations of promising therapies in
animal models. Program staff regularly interact with basic scientists, other government
agencies, and pharmaceutical firms to acquire novel compounds for evaluation.