AIDS Research at the NIH: A Critical Review

million in FY 1991. Most NEI AIDS funds go to the SOCA program (see below) and to an intramural clinical
trials program, with much smaller extramural awards in diagnostic methods, animal models, neuroscience
and diseases related to HIV (principally CMV, toxoplasma and microsporidia-related retinitis).
Basic research. Of the 11 non-SOCA extramural awards, two involve developing mouse models for CMV
retinitis; one small training grant targets ocular manifestations of SIV in primates; two are attempting to
develop new methods to diagnose HIV, HHV-6 and CMV in people with AIDS; three are looking at other
mechanisms of HIV- and/or CMV-induced optic neuropathy; and one each is looking at ocular
toxoplasmosis and ocular microsporidiosis in AIDS.
Intramural clinical trials. NEI conducted the pivotal study which led to FDA approval of foscamet for CMV
retinitis. In FY 1991 NEI spent $1 million on its intramural clinical trials, developing a surgical implant to
deliver ganciclovir directly to the eye over a period of months; this trial will begin in mid-1992. NEI's
Laboratory of Immunology is jointly carrying out epidemiology on the ocular manifestations of AIDS in
children with the NCI Pediatrics Branch, following 150 children. They have recently identified VZV retinitis
as a new opportunistic infection in these children. These conditions are a diagnostic challenge, since
children - especially infants - are less likely to report visual problems. NEI also studied the ocular toxicity
of ddl in children. NEI participated in a preliminary study of oral 566c80 for ocular toxoplasmosis.
Studies of the Ocular Complications of AIDS (SOCA) is a series of three cooperative agreements (U01s)
funded by NEI to conduct clinical trials of interventions for eye pathogens in people with AIDS and HIV
infection. The structure and operations of SOCA are a dramatic contrast with those of the ACTG system,
also funded with cooperative agreements. SOCA was initiated in 1988 and funded in 1989, and is
supported by over $3 million a year. Two U01s go to fund the Chairman's Center (PI Douglas Jabs, MD)
and the Coordinating Center (PI Curtis Meinert, PhD), both at Johns Hopkins in Baltimore. The third U01
supports the Fundus Photograph Reading Center in Madison, Wisconsin, where retinal photographs are
analyzed. The entire SOCA system is subcontracted and administered from Hopkins. [Imagine the ACTG
funded as a series of subgrants from Harvard and Stanford and you'll get the picture.] Thus, the $2.8
million which supports the 11 clinical centers around the country is all filtered through Curtis Meinert's
Coordinating Center at Hopkins. Each SOCA unit, with the exception of Baylor College in Houston, also
receives ACTU funds. The SOCA took a radically different approach from the ACTG. Rather than trying
to do everything, the SOCA tried to do one thing well. In this case, SOCA took on the most pressing single
question about CMV retinitis -- which treatment is better, foscamet or ganciclovir? -- and answered it in just
18 months.
Fundina + Future Plans. NEI's AIDS program spent $5,680,000 in FY 1991, 2.2% of its total budget and
0.7% of the NIH AIDS total. NEI requested an increase to $14,368,000 in FY 1993, but the President
granted a mere $319,000. Included in the NEI's request were the following four programs:
* $2 million more in the SOCA program for a total of $5.5 million;
* $2.9 million in new funds to compare oral with intravenous gancidclovir;
* $3 million in new funds to study CMV prophylaxis;
* $1.4 million to triple current funds to study animal models of the ocular complications of AIDS.
Recommendations
* NEI should work on elucidating the ocular immune defects (possible vascular breakdown, cytokine
involvement, etc.) which lead to eye disease in AIDS.
* NEI should dispense with the delayed treatment arm of its new study of intraocular implants for
CMV retinitis. The SOCA study should have made clear that PWAs are generally unwilling to be
randomized to delayed treatment regimens.

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