The identification of intact HIV proviral DNA from human cerebrospinal fluid

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• The human immunodeficiency virus type 1 (HIV-1) establishes persistent reservoirs in various body compartments, including the central nervous system (CNS).
• Understanding the extent and characteristics of the CNS HIV reservoir is crucial for developing effective HIV cure strategies and managing HIV-associated neurocognitive disorders.
• The intact proviral DNA assay (IPDA) offers a novel method to quantify potentially replication-competent HIV DNA.

Purpose of the Study:

• To evaluate the quantity and characteristics of the HIV-1 DNA reservoir in the cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) of people with HIV (PWH).
• To investigate the association between HIV DNA levels in the CSF and cognitive dysfunction in PWH, irrespective of antiretroviral therapy (ART) status.
• To assess the utility of IPDA for studying CNS HIV reservoirs.

Main Methods:

• Analysis of HIV-1 DNA (intact, 5' defective, 3' defective) in CSF and PBMC samples from PWH using the intact proviral DNA assay (IPDA).
• Comparison of HIV DNA levels between CSF and matched/unmatched PBMC samples.
• Correlation of HIV DNA levels with cognitive performance assessed by a battery of nine neuropsychological tests.

Main Results:

• Total HIV DNA was significantly higher in CSF compared to matched PBMCs.
• Intact HIV DNA was frequently detected in CSF and showed a strong correlation with levels in PBMCs.
• Higher CSF HIV DNA levels, though not global cognitive performance, correlated with worse executive function.

Conclusions:

• The findings confirm the presence of a substantial HIV-1 DNA reservoir within the CNS of PWH, detectable in CSF.
• Intact HIV DNA in the CSF suggests a potential source for viral persistence and rebound.
• This study highlights the importance of the CNS reservoir in HIV pathogenesis and provides a valuable methodology for future HIV cure research.