AIDS Research at the NIH: A Critical Review

system that often accompany AIDS;
* To develop predictive criteria for the onset and severity of neurological symptoms in HIV+ persons;
* To develop methods to deliver antiviral agents through the blood-brain barrier;
* To investigate the differing course and manifestations of the disease in children and adults;
* To study the role of the immune system and substances it elicits (such as cytokines and TNF)
during viral infection and their effects on the brain;
* To conduct studies of other retroviruses, such as HTLV-1, applying findings to HIV;
* To include minority populations in clinical studies of the neurological complications of AIDS.
Extramural Research. In 1991, 72% - or $11.9M - of NINDS's AIDS support for extramural research -
went to fund 25 R01s, 4 R29s and 7 P01s. Two grants supported diagnosis of the neurological Ols of
AIDS. One correlated the presence of JC virus DNA in the CSF with PML. The other was an investigation
of the use of NMR to distinguish CNS toxoplasmosis from CNS lymphoma in AIDS.
Primary HIV Infection of the Nervous System. 26 of NINDS' 29 basic AIDS research grants go to the
study of the neuropathogenesis of HIV infection, including the pathogenesis and natural history of AIDSrelated encephalopathy; peripheral neuropathy and myopathy; the development of animal models for the
neurological effects of HIV; and potential therapeutic approaches.
14 grants studied the pathogenesis of CNS involvement in AIDS, including identification and
characterization of neurotropic variants of HIV; identification of receptors for HIV in the brain; the extent and
distribution of cortical atrophy; the role of macrophage or astrocyte produced cytokines in mediating CNS
damage; correlation of regional CNS damage with the local presence of HIV, the CD4 surface receptor,
HLA-DR MHC marker; the role of microglia-derived IL-1 in inducing astrogliosis and neuronal dysfunction
and degeneration, as well as immunosuppressive neuroendocrine responses; the effects of HIV and its
proteins (e.g. gpl20) on the function and structure of specific cells of the nervous system.
In addition, NINDS funds four R01s to assess the natural history of the neurological manifestations of HIV
infection in children (3 grants) and gay men (1 grant).
NINDS-supported researchers are also investigating the pathogenesis of other lentiviral infections in other
species (visna virus, CAEV, FeLV and borna disease) as animal models for HIV infection.
Finally, two grants are investigating therapies for the neurological effects of HIV infection. One grantee is
investigating the use of probenecid and salicylic acid to alter the distribution of AZT between the CNS and
the plasma, in the hope of achieving higher levels in the brain. The other is investigating myopathy in HIV
infection, both HIV-associated and AZT-associated, comparing corticosteroid therapy with AZT withdrawal
in the treatment of this condition.
AIDS Dementia Centers. Seven NINDS-supported research projects are studying AIDS Dementia
Complex and other neurological complications of HIV infection. Of these, six support AIDS Dementia
Centers at UNC (Chapel Hill), Johns Hopkins, U. Miami, U. Minnesota, U. Pennsylvania and U. Maryland.
These awards total $6 million and utilize a diverse array of molecular, cellular, diagnostic and
epidemiological tools to improve understanding about the diverse neurological sequelae of HIV and AIDS.
Intramural Research. NINDS's intramural AIDS budget for 1991 was $4,711,973 The following is a list
of intramural laboratories and their AIDS-related projects: Laboratory of Viral and Molecular
Pathogenesis: Recombinant Chimeric Glycoproteins and Recombinant Pseudotype Viruses for the Study
of HIV Replication and HIV Receptors; Studies of HIV-1 Neuropathogenesis; JC Virus Induced
Demyelination, Progressive Multifocal Leukoencephalopathy, in the Immunodeficient AIDS Patient; HIV-1
Infection of the CNS in the Pediatric AIDS Patient; Neurotropism of HIV-1; Viral Gene Therapy for HIV

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