AIDS Research at the NIH: A Critical Review

of Molecular Biology: Studies on the mechanism of retroviral DNA integration; AIDS related proteins -
structure and function; Study of the potential use of catalytic antibodies against AIDS; Genetics +
Biochemistry Branch: CD4 receptor structure/function project; Target ribozymes to HIV sequences;
Laboratory of Molecular and Cellular Biology: Function of DNA virus genomes in animal cells;
Regulation of HIV by AAV. These laboratories have 1) identified of two glycosylation sites on the CD4
molecule required for proper protein folding and transport to the cell surface; 2) identified the protein
necessary for integration of HIV into the host genome and the development of an assay to screen for
inhibitors of this enzyme; 3) generated preliminary evidence suggesting that the human parvovirus AAV re
gene blocks growth of infectious HIV by inhibiting the function of the HIV tat gene; 4) shown inhibition of
HIV gpl20-induced impairment of signal transduction in human CD8+ cells by sCD4. The heavy emphasis
on molecular biology and related disciplines in NIDDK's intramural AIDS program is disappointing. Work
of this kind is heavily subsidized elsewhere and NIDDK's efforts don't particularly stand out from the crowd,
except for the research on the HIV-1 integrase and the negative regulatory properties of the AAV re gene.
Perhaps NIDDK's intramural branches could supplement NIDDK's extramural work on wasting and related
topics.
For FY 1993, NIDDK wanted to double its AIDS FTEs from 10 to 20 for intramural research projects. If
money were available, NIDDK should not simply double its efforts in the area of molecular virology and
drug design, but should also attempt to involve intramural researchers in projects on wasting and related
metabolic disturbances, gastrointestinal infections and abnormalities, neuroendocrine and immune system
interactions, thymic pathology, hematopoietic dysfunction, and renal complications.
Recommendations:
* NIDDK's request for an additional $10M for FY 1993 should be honored and funded by Congress.
* NIDDK should consider initiating collaborative efforts with the NIAID-funded ACTG, specifically in
the areas of nutrition and wasting, and gastrointestinal infections (crypto- and microsporidiosis, etc.).
* NIDDK should fund work on opportunistic enteric pathogens; the gastrointestinal mucosal immune
response in HIV infection; the mechanisms of AIDS enteropathy and malabsorption;
microsporidiosis; enteropathic/enteroadherent E. coli infection; herpesvirus infection of the GI tract;
cryptosporidiosis: animal models and in vitro screening assays for drug development; interactions
between HIV and hepatitis viruses; hepatobiliary pathology in AIDS; aphthous and large idiopathic
ulcers in the GI tract.
* Further research the role of the thymus, the effects of neuroendocrine hormones and peptides on
lymphocyte development and function, and on the regulation of the immune response.
* Further study the renal toxicities of drugs currently in use in HIV infection.
* Study effects of transplant-associated immunosuppressive chemotherapy in HIV-infected persons
at various stages of disease.
IVl. National Eye Institute (NEI
NEI was established in 1968 (P.L. 90-489) to support "basic and applied research, including clinical trials,
related to the cause, natural history, prevention, diagnosis, and treatment of disorders of the eye and visual
system." Carl Kupfer, MD, is its first and hitherto only director. NEI's commitment to AIDS was $5.68

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