NIH Funding Opportunity: Biotypes of CNS Complications in People Living with HIV

Funding Opportunity Number: RFA-MH-24-235

Letter of Intent: November 11, 2023
Application: December 11, 2023


Central Nervous System (CNS) complications, including mild to moderate cognitive impairment and adverse mental health outcomes, are significant comorbidities among individuals living with HIV on antiretroviral therapy (ART). Despite two decades of clinical studies and many clinical trials aimed at improving outcomes related to CNS complications associated with HIV, results have been largely disappointing, with most trials showing minimal or no improvement in neurocognitive function. Researchers are now recognizing that, in addition to inflammation at the cellular level, various patient-level factors such as comorbid conditions (e.g., cardiovascular, metabolic, substance use), concomitant neurological diseases, persistent CNS viral reservoirs, long-term effects of chronic HIV infection, immune system dysfunction, social and structural factors, concomitant drug use and pharmacological treatments including ART-related toxicity can influence CNS pathogenesis and resulting outcomes.

The complexity of these multifactorial pathogenic pathways leads to heterogeneity in outcomes. There has been a shift in psychiatry towards incorporating a neurobiological understanding of CNS disease and patient outcomes rather than solely focusing on clinical phenomenology. To better understand the heterogeneity of CNS outcomes in individuals living with HIV, it is necessary to collect and analyze biological measures related to the etiologies and pathophysiological pathways involved in causing such complications. This effort can help identify biologically distinct disease phenotypes (based on mechanisms), known as biotypes, and allow for the retrospective modeling of disease conditions enabling development of personalized treatment strategies (precision medicine) to mitigate negative CNS outcomes in people living with HIV.

For more detailed information, please see the funding announcement website.