Limited Competition to Convert the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study Cohort to a Research Resource Grant

Presenter:

Dianne Rausch, Ph.D.
Division of AIDS Research

Goal:

The goal of this initiative is to convert the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort, a cohort of individuals living with HIV that have been followed for almost 20 years, to a stand-alone research resource. This is the only HIV cohort that focuses primarily on the impact of HIV on central nervous system (CNS) pathology and neurological clinical manifestations. Maintaining this highly valuable cohort as a resource may enable researchers to continue collecting data appropriate to NeuroHIV and the co-occurring comorbidities that are now associated with HIV as a chronic disease.

Background:

CNS disease associated with HIV continues to persist in people living with HIV (PLWH) despite effective antiretroviral therapy (ART). Although excellent virologic control in the periphery and brain has been achieved, CNS complications including neurologic, neuropathogenic, and mental health problems persist. Despite efforts to alleviate CNS disease outcomes associated with HIV, there has been limited success with clinical trials due to heterogeneity of etiologies and presentation. Effective ART treatment can significantly improve life expectancy for PLWH which can then be accompanied by aging-associated chronic comorbidities that can impact CNS disease such as variable treatment regimens, legacy effects, substance use, and immune dysfunction. In addition, achieving sustained viral remission (HIV Cure) in PLWH is a high priority and the CNS is an important anatomical viral reservoir. CHARTER is one of the very few long-term cohorts to-date that has followed HIV-associated CNS comorbidities and CNS viral dynamics (Cerebral Spinal Fluid Escape) in the ART era over the past two decades.

Starting in 2003, the CHARTER researchers have monitored cohort participants in cross-sectional studies and followed participants longitudinally to understand CNS complications associated with living with HIV. CHARTER has six clinical sites that are located across the U.S. The key focus areas of the studies have been neurocognitive and neurological disorders prior to ART and during ART; comorbid risk factors such as substance use; the distribution of ART in the CNS; the impact of aging on CNS complications; the impact of metabolic complications on the CNS; peripheral neuropathy; the role of viral and host genetics; and, acute/early infection of the CNS; and neuroimaging biomarkers of CNS co-morbidities. These studies have resulted in a rich data repository containing neuro-medical data, neuropsychological assessments, psychiatric and drug abuse variables, treatment regimen data, neuroimaging data catalog, and viral and host genetics data. In addition, CHARTER has data on lifetime and interval substance use for 15 substances as well as lifetime and interval DSM-IV substance use diagnoses for all participants. Overall, the CHARTER database contains over 5 million datapoints and over 4,000 individually collected, well cataloged items.

This limited competition initiative aims to support continued maintenance of this long-standing CHARTER cohort of HIV/CNS disease to address the scientific program priorities of the NIMH and co-sponsors NINDS, NIA, and NIDA.

Scope and Research areas to be supported by CHARTER:

• Understand the pathogenic mechanisms and genetic factors involved in the pathogenesis of HIV-associated CNS dysfunction including cognitive, neurologic, and mental health outcomes;
• Understand mechanisms of establishment and persistence of the HIV viral reservoir in the CNS;
• Assess the impact of new therapeutic strategies on CNS complications associated with HIV infection and eradication of HIV from the CNS/myeloid reservoirs;
• Assess the impact of living with HIV in an increasingly aging population with other chronic illnesses and substance use disorders.