Clinical Relevance of Total HIV DNA in Peripheral Blood Mononuclear Cell Compartments as a Biomarker of HIV-Associated Neurocognitive Disorders (HAND)

Abstract

The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. It is hypothesized that the critical events initiating this condition occur outside the brain, particularly in the peripheral blood. Diagnoses of HIV-induced neurocognitive disorders largely rely on neuropsychometric assessments, which are not precise. Total HIV DNA in the peripheral blood mononuclear cells (PBMCs), quantified by PCR, correlate with disease progression, which is a promising biomarker to predict HAND. Numerous PCR assays for HIV DNA in cell compartments are prone to variation due to the lack of standardization and, therefore, their utility in predicting HAND produced different outcomes. This review evaluates the clinical relevance of total HIV DNA in circulating mononuclear cells using different published quantitative PCR (qPCR) protocols. The rationale is to shed light on the most appropriate assays and sample types used to accurately quantify HIV DNA load, which predicts severity of neurocognitive impairment. The role of monocytes as a vehicle for trafficking HIV into the CNS makes it the most suitable sample for determining a HAND associated reservoir. Studies have also shown significant associations between monocyte HIV DNA levels with markers of neurodamage. However, qPCR assays using PBMCs are cheaper and available commercially, thus could be beneficial in clinical settings. There is need, however, to standardise DNA extraction, normalisation and limit of detection.

Development of a multiplex real-time PCR assay for the simultaneous detection of four bacterial pathogens causing pneumonia

“…The housekeeping gene HBB was used to ensure proper sampling and adequate target amplification for internal quality [ 23 ]. Although microscopy can determine sputum quality based on the number of polymorphonuclear leukocytes (≥10) and squamous epithelial cells (<25) [ 24 ], the use of HBB as an internal control correctly determines the quality of the specimen, procedure of nucleic acid extraction, and presence of PCR inhibition [ 25 , 26 ].…”

Peripheral blood lymphocyte proviral DNA predicts neurocognitive impairment in clade C HIV

“…The association of this major peripheral reservoir of HIV-1 DNA with neurocognitive impairment has significant pathological and clinical implications, particularly in the diagnosis and monitoring of the disease. Proviral DNA can be used to understand progression of HIV-associated neurocognitive impairment, particularly in subtle forms of the disease where symptomatic monitoring is difficult (Ruhanya et al 2017). Theoretically, HIV in these cells can be targeted when devising therapeutic strategies to HIV-associated neurocognitive impairment.…”

“…HAND affects 40-70% of HIV-1-infected patients (Williams et al 2014;Yusuf et al 2017), despite immune reconstitution and viral suppression because of combination antiretroviral therapy (cART) (Cysique et al 2015). The exact mechanism of HAND pathogenesis is not known, but it is thought to be a complex interaction of factors including cellular targets, viral factors, and the immune response (Saylor et al 2016;Carroll and Brew 2017;Ruhanya et al 2017). Evidence from experimental models and human studies show that HAND pathogenesis involves a seeding of peripheral HIV-1 into the central nervous system (CNS) (Price et al 2007).…”

Application Value of Machine Learning Method in Measuring Gray Matter Volume of AIDS Patients

“…It has estimated that 15–55% of all HIV-1 cases have HAND [ 4 – 6 ]. Asymptomatic neurocognitive impairment (ANI), mild nerve HIV-associated mild neurocognitive disorder (MND) and HIV-associated dementia (HAD) are different forms of HAND [ 7 ]. After highly active antiretroviral therapy (HAART), HAND still exists and affects survival, quality of life, and daily functioning [ 8 ].…”