HNRC Home Studies Accomplishments & Research Directions
Accomplishments and Research Directions

HNRC Scientific Themes

  1. What attributes of the virus, host, and host-virus interaction determine presentation of HIV-associated neurobehavioral disorders?
  2. What are the actual mechanisms by which the host-virus factors generate neural injury and neurobehavioral disorders?
  3. What is the role of co-pathogens and comorbidities in neuroAIDS?
  4. How can treatments be optimized to prevent or ameliorate neuroAIDS?
  5. What is the effect of HIV neurocognitive complications on everyday functioning; do treatments that correct neurocognitive abnormalities restore productivity and quality of life?

  1. What attributes of the virus, host, and host-virus interaction determine presentation of HIV-associated neurobehavioral disorders?

    From the aspect of the virus, what are the relationships of molecular diversity (e.g., of HIV-1 envelope sequences) and neurovirulence? What are the mechanisms for increased molecular diversity in brain or CSF derived virus versus plasma or lymph nodes? Are there clade-specific differences in neurotropism and neurovirulence, and what are the molecular mechanisms underlying these? Examples of questions from the host side may include questions such as the importance of polymorphisms in genes encoding various neuroinflammatory signaling molecules (e.g., MCP-1, STF-1) or their co-receptors in facilitating vulnerability to neuroAIDS. From an international perspective, if such host genotype vulnerabilities are found, are they distributed differently in various populations, such as those from North America/Europe, India, China, or Africa?

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Selected Findings from HNRC-supported Projects

  1. Molecular Mechanisms
  2. Neuroprotective Strategies
  3. Acute/Early (AEH) Infection
  4. Cofactors/HIV Associated Neurocognitive Disorder (HAND)
  5. Cross-Cultural Applications of Assessment Methods
  6. Optimal Antiviral Treatments/HIV Associated Neurocognitive Disorder (HAND)

 

  1. Molecular Mechanisms

    From the standpoint of molecular mechanisms, several HNRC studies have focused on the problem of "protein mismanagement" in HIV diesease.  For example, HNRC-associated investigators noticed increased frequency of alpha synuclein in the substantial nigra of persons dying with HIV disease (Khanlou et al., 2009) and electron microscopy and double labeling studies confirmed presence of aggregated A-proton in lysosomes and autophagosomes of such cases.  Additional studies have suggested that in patients with HIV associated encephalitis (HIVE) autophagy is abnormally activated and that these alterations may be exacerbated with aging.

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HNRC Contributions to Methods Development

  1. Refining the neuropsychological battery
  2. Norms appropriate to special populations
  3. Operationalizing the diagnosis of HIV-associated neurocognitive disorders
  4. Reliable measurement of neurocognitive change
  5. Instruments for documenting "real life" implications of HIV neurocognitive impairment
  6. Innovations in brain imaging
  7. Improved statistical approaches
  8. Novel methods for analyzing neurodegeneration and measuring neuronal populations, proteins and select receptors

  1. Refining the neuropsychological battery

    At the Center's inception in 1989 we deployed a comprehensive neuropsychological ensemble since, at that time, we lacked systematic information on qualitative and quantitative features of HIV-associated neurocognitive impairment at different stages of disease. Hence, it was necessary to assemble a battery that had broad coverage, as well as sufficient sensitivity to detect what might be subtle, early changes. The early experience of the HNRC allowed us to make substantive contributions to the NIMH Consensus Conference that resulted in the publication of the NIMH recommended neuropsychological battery (Butters et al., 1990).

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The HNRC as a National and International Resource

The HNRC has come to be recognized for its expertise on the neurobehavioral complications of HIV both at the national and international levels. As mentioned above, HNRC investigators contributed fundamentally to the development of the NIMH consensus recommendations for neuropsychological testing in HIV (Butters et al., 1990) and was again involved in a more recent NIH position statement (Bloom & Rausch, 1997). HNRC investigators also contributed to the development of the neuropathological standards for classifying HIV disease (cf, the contributions of Clayton Wiley, while at the HNRC, to the Budka et al., 1991 consensus statement) and most recently, participated in the NIH work group “A Critical Re-Examination of Adequacy and Utility of AAN 1991 Definitional Criteria” (NIMH/NINDS: Frascati, Italy, 6/13/05).

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Future Directions

The HNRC will focus broadly on the shifting phenomenology and course of neuroAIDS and
neuroAIDS in resource-limited settings.

Shifting Phenomenology and Course of NeuroAIDS

In the developed world, every year new antiviral treatments have emerged, targeting multiple pathways involved in HIV pathogenesis. These therapies have had the effect of transforming what was once a debilitating, and often rapidly fatal, disease into a chronic infection with which many people survive for very long periods of time often with minimal or only modest medical symptoms.

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