Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources

Area of Science:

• Neurovirology
• Immunology
• Infectious Diseases

Background:

• Cell-free human immunodeficiency virus (HIV) in cerebrospinal fluid (CSF) originates from both systemic and central nervous system (CNS) tissues.
• Antiretroviral therapy (ART) initiation leads to decreased CSF HIV RNA, with kinetics influenced by the dominant virion source.
• In advanced HIV disease, the primary source of CSF virions is hypothesized to shift from systemic to CNS tissues.

Purpose of the Study:

• To identify the sources of HIV virions in CSF by modeling treatment-associated HIV dynamics.
• To investigate the compartmentalization of HIV in the CNS during treatment.

Main Methods:

• Three patient groups were studied: early HIV disease, advanced HIV disease, and HIV-associated dementia (HAD).
• All patients initiated highly active antiretroviral treatment (HAART) and underwent serial lumbar punctures and phlebotomies.
• HIV RNA levels in CSF and plasma were measured to model viral dynamics.

Main Results:

• Patients with advanced HIV disease showed a slower decline in CSF HIV RNA compared to plasma HIV RNA.
• Patients with early HIV disease exhibited similar rates of decline in CSF and plasma HIV RNA.
• Patients with HAD displayed persistently high CSF HIV RNA levels despite significant reductions in plasma HIV RNA.

Conclusions:

• HIV dynamics in CSF and plasma become increasingly independent with advanced HIV disease, with the largest discrepancy observed in HAD.
• CNS tissues, particularly brain parenchyma, may serve as a major, independent source of CSF HIV RNA in advanced disease and HAD.
• CNS-targeted treatment strategies may be necessary to effectively manage HIV infection in the brain and eradicate the virus in patients with HAD.