Cerebrospinal fluid (CSF) HIV escape refers to clinical settings in which the magnitude of central nervous system (CNS) HIV infection, reflected in the CSF HIV RNA concentration, is equal to or exceeds the HIV RNA concentration measured in blood during antiretroviral therapy (ART). Three types of CSF escape have been identified: Neurosymptomatic, in which there is clear clinical evidence of CNS injury, Asymptomatic without documented injury, and Secondary provoked by a non-HIV CNS infection. Each of these develops in a setting where ART exerts less effect on CNS than systemic HIV infection, thereby permitting detailed examination of a relatively ?isolated? CNS viral population. This Supplemental proposal extends our ongoing research project in two ways.
Specific Aim S1 introduces two rare and invaluable sample sets for molecular virological analysis to define the origins of CSF HIV populations in Neurosymptomatic and Secondary CSF Escape.
Specific Aim S2 supports use of novel technology to measure a large array of CSF and blood biomarkers to better characterize the inflammatory and neurological features of all three types of CSF escape. Overall, these Supplementary studies will advance our understanding of the exchange between systemic and CNS HIV infection, including the contributions to from a CNS HIV reservoir and ongoing seeding from the blood. This understanding will advance the clinical recognition, diagnosis and management of these unusual aspects of treated HIV, and provide broader insights into the origins, pathogenesis and treatment of CNS HIV infections.
While antiretroviral therapy has a remarkable impact on severe central nervous system (CNS) infection caused by HIV, the virus likely establishes a long-term reservoir in the brain. The proposed studies which focus on settings in which CNS infection may ?escape? from treatment control not only have practical value for diagnosis and treatment, but broader implications for understanding the origins of CNS HIV infection, the CNS HIV reservoir and approaches to its mitigation and cure.
| Premeaux, Thomas A; D'Antoni, Michelle L; Abdel-Mohsen, Mohamed et al. (2018) Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals. J Neurovirol : |
| Farhadian, Shelli F; Mehta, Sameet S; Zografou, Chrysoula et al. (2018) Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 3: |
