AIDS Research at the NIH: A Critical Review

Infections Using Defective Interfering HIV Particles. Laboratory of Molecular and Cellular Neurobiology:
Investigation of the Molecular Pathogenesis of Demyelination and Myelin Abnormalities in the Central and
Peripheral Nervous System of AIDS Patients. Medical Neurology Branch: Neuroimmunological studies
of HIV+ asymptomatics; neuromuscular diseases associated with HIV; dorsal root ganglia and neuropathy;
immune responses in HIV-Related inflammatory myopathy; muscle cell susceptibility to HIV; inflammatory
myopathy; myotoxicity of AZT; polymyositis, dermatomyositis, and inclusion body myositis; HTLV-1
myopathy and T-cell leukemia. Laboratory of Central Nervous System Studies; Epidemiology of Tropical
Spastic Paraparesis (TSP) and other HTLV-1-Caused Diseases in the western Pacific; retrovirus antibodies
in Jamaican schizophrenics; HIV+ chimpanzees vaccine studies; SIV and HTLV-I in macaques.
Developmental and Metabolic Neurology Branch: Synthesis of Inhibitors of Protein Myristylation.
Neurolmmunology Branch; TSP; retroviral involvement in multiple sclerosis; HTLV-1 envelope gene
products; HTLV-2.
Future plans. NINDS had quite a hefty little tome for its FY 1993 wish list, including:
* Extramural expansion of $4.9M for 12 gmts to study of neuro-AIDS in adults and children;
neurovirulent strains of human retroviruses; cofactors affecting the growth of neurovirulent strains;
opportunistic infections; CNS control of the immune response; viral alterations of nerve cells; HIV's
role in neuronal damage, including the effects of cellular toxins, lymphokines and HIV proteins on
the nervous system; and other retroviruses which affect the central and peripheral nervous systems.
* $2.8M for 5 new FTEs to study neurotoxins produced by HIV+ cells in the CNS; mechanisms of
action and treatments for neurological HIV manifestations; neurovirulence of certain HIV strains and
the mechanism of their molecular control; cooperative clinical research on the effects of HIV
infection on neurological, behavioral, cognitive and affective function, in order to develop diagnostic
procedures for use in longitudinal studies of HIV infection;
* New extramural efforts totaling $7.6M to study; HIV's effects in the developing and pediatric CNS;
collaboration with ACTG to identify and evaluate treatments for neuro-AIDS and assess the
neurological side effects of new drugs; prevention and control of neurological disease in pediatric
AIDS; new animal neuro-AIDS models; HTLV-1 and the CNS; support of centers studying large
populations of PWAs, emphasizing children and people of color longitudinal studies to assess early
neurological effects; and the effects of maternal immune response on transmission to neonates.
* $1 M for 6 new FTEs to study neuroimmunological response to retroviral infection; HIV-1 products
in neural (and lymphoid) cells; and to develop new assays and reagents to detect low levels of HIV
infection in CNS cells.
With its 7.9% budget rise for FY 1993, NINDS be unable to fund most of these initiatives.
Recommendations:
* Congress should fully fund NINDS's original budget request for FY 1993;
* NINDS should allocate additional resources for the development and evaluation of novel
therapeutics for the neurological manifestations of HIV infection. A search for inhibitors of cytokines
and neurotoxins (e.g. quinolinic acid and other kynurenine pathway metabolites) implicated in the
pathogenesis of ADC, as well as for agents that might protect cells of the CNS from damage (e.g.
competitors for the NMDA receptor) should be pursued;
* NINDS should increase its extramural support for investigations of the mechanisms of HIV-and

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