Proviral DNA Integration in Human Peripheral Blood Mononuclear Cells: Biomarkers of HIV Associated Neurological Impairment

Abstract

Purpose: Historically, HIV decreased an individual’s survival due to opportunistic infections and malignancy. Since the introduction of antiretroviral therapy, many complications of HIV have declined. However, half of HIV+ individuals still experience cognitive impairments. These conditions are classified as HIV-associated neurocognitive disorder (HAND). This is a significant portion of the HIV population with issues maintaining daily functioning. While there are current objective measurements of disease progression with markers such as HIV viral load and CD4 cell counts, these have been found to be poor indicators of neuropsychometric performance. Therefore, there is a need for objective measures that could serve as prognostic biomarkers for the development HAND progression, stability or regression of disease. This could lead to further discovery of therapies and interventions for HAND. This research project focuses on peripheral blood mononuclear cells (PBMCs). The amount of HIV DNA integration may serve as a potential biomarker alone or in correlation with other inflammatory proteins from 121 male and female human subjects across three highly affected races. Methods:Enrolled participants enrolled underwent thorough evaluations, including a blood draw and full battery of neurocognitive functional tests. To determine the level of integrated of HIV, PBMCs were isolated from participant blood samples. Genomic DNA was isolated using DNAzol reagent. HIV DNA integration was then determined and quantified with a nested Alu-Gag PCR. Results: The levels of HIV DNA integration were correlated with measures of neurocognitive dysfunction and previously identified plasma biomarkers that are associated with neurocognitive dysfunction. The level of HIV DNA integration may serve as a prognostic biomarker of HIV-associated neurological impairment. Conclusions:These results may correlate with modifications of cellular function by the HIV DNA integration. Future directions will include self-report questionnaires regarding the participant’s perception of neurocognitive decline affecting their everyday living. Correlations between perception of neurocognitive impairment, discovered plasma, and HIV DNA integration biomarkers of neurocognitive decline could improve prognostic outcomes of HAND.