Abstract
ObjectivesTo determine the contribution of peripheral blood mononuclear cells’ (PBMCs) HIV DNA levels to HIV-associated dementia (HAD) and non-demented HIV-associated neurocognitive disorders (HAND) in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART).MethodsEighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL) were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points.ResultsAt baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03). Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05). Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 106 PBMC). Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04), and higher in those with no ART treatment during HIV infection 1st year (p = .03). Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03), and motor-coordination (p = .02-.12) to a lesser extent.ConclusionsPBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression.
Highlights
HIV-associated neurocognitive disorder (HAND) occurs despite combined antiretroviral therapy with long-term viral suppression and minimal or no neuropsychiatric confounds [1,2,3]
peripheral blood mononuclear cells’ (PBMCs) HIV DNA plays a role in HIV-associated dementia (HAD) pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression
While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression
Summary
HIV-associated neurocognitive disorder (HAND) occurs despite combined antiretroviral therapy (cART) with long-term viral suppression and minimal or no neuropsychiatric confounds [1,2,3] In such patients, the main neuropathological process responsible for brain damage remains to be elucidated. HIV persistence may cause low-level immune activation via diverse mechanisms, including lowlevel residual viremia, which is detectable in the majority of HIV-infected individuals on longterm cART by ultrasensitive assays[4]. In this context, it remains unclear whether the persistent immune activation is primarily driven by HIV DNA reservoirs (and persistent low-level viremia) in the systemic compartment versus those in the Central Nervous System (CNS). HIV-related brain injury principally results from HIV reservoirs within brain cells (macrophages, glial cells and astrocytes), which triggers chronic immune activation within the CNS separately from the systemic compartment
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