OI Backgrounder, Opportunistic Infections Research

Preclinical Of

the most active compounds have progressed into animal model evaluation. This service is
available to any scientist who has a potential antiviral compound and is unable to test it.
Currently, the ARB also manages a separate DAIDS-supported program of five
contracts, now in their third year, for the development of antivirals for treating CMV
infection in people with HIV disease or those who are otherwise immunosuppressed.
Although the FDA approved the use of ganciclovir for treatment of CMV retinitis in June
1989, problems with the drug exist (for example, toxicity and lack of oral delivery), and
thus, the search for better therapies continues. Several promising anti-CMV compounds
developed by these contractors are now being evaluated in animal models.
Animal Model Contracts
Seven research contracts support 11 animal models of human viral infections. -
Experimental compounds provided by investigators can be evaluated in these models to
determine the compound's toxicity and efficacy. These models include a guinea pig model
of genital herpes; an African green monkey model for simian varicella; guinea pig and
mouse models for CMV infections; and rabbit and nude mouse models for papillomavirus
infections. Several compounds have shown promising effectiveness in the mouse model of
CMV infection. The most thoroughly evaluated of these, HPMPC, was significantly more
effective than ganciclovir. Furthermore, it was equally effective whether given with
intermittent (every 3 to 7 days) dosing or with the more traditional daily dosing. This may
be an important advantage if the drug will be given in combination with other therapeutic
agents. In a related development, a topical form of PMEG, a compound similar to
HPMPC, showed efficacy against papillomavirus-induced warts in the cottontail rabbit.
Basic Research in Immunology and Infectious Diseases
Since NIAID's beginnings in 1948, the Institute has directed a major portion of its
efforts to illuminating the molecular mechanisms underlying infectious diseases. The scope
of the Institute's research has continually expanded to accomodate the growing recognition
of disease-causing parasites, bacteria, fungi, and viruses. This ongoing effort now has
increased urgency because of HIV disease and its attendant Ols. In the last few years,
basic research has provided an increasingly sophisticated understanding of infectious agents
and of the immune system's remarkable capacity to produce powerful, appropriate, and
self-limiting responses to infection. NIAID-supported scientists have pioneered many areas
of infectious disease research.
Joint Workshop on Opportunistic Infections
In September 1989, DTB, ARB, and the Medical Branch of DAIDS held a joint
workshop titled "Future Directions in Discovery and Development of Therapeutic Agents