Peripheral blood HIV DNA is associated with atrophy of cerebellar and subcortical gray matter

Abstract

Objective: We evaluated regional brain volumes and cerebral metabolite levels as correlates of HIV DNA in peripheral blood mononuclear cells (PBMCs). Methods:In this cross-sectional study, 35 HIV1 subjects aged $40 years (25 with detectable PBMC HIV DNA; 10 with HIV DNA ,10 copies/10 6 cells, the threshold of detection) and 12 seronegative controls underwent structural brain MRI and magnetic resonance spectroscopy at 3 T. HIV1 subjects were on combination antiretroviral therapy $1 year; all but 1 had plasma HIV RNA ,50 copies/mL. We used logistic regression to evaluate relationships of likely predictor variables to the outcome of PBMC HIV DNA detectability in the HIV1 subjects. Effects of serostatus and HIV DNA on regional brain volumes (normalized to intracranial volume) and on metabolite ratios over creatine were evaluated by analyses of covariance, controlling for age.Results: Relative to the HIV1 group with undetectable HIV DNA, subjects with detectable HIV DNA demonstrated decreased volumes of cerebellar (214%, p 5 0.020) and total subcortical (210%, p 5 0.024) gray matter. Compared to healthy controls, only the detectable HIV DNA group showed significant (p , 0.05) enlargement of lateral ventricles and volumetric reductions of caudate, putamen, thalamus, hippocampus, nucleus accumbens, brainstem, total cortical gray matter, and cerebral white matter. Detectable HIV DNA was not associated with significantly altered cerebral metabolite levels. Glu 5 glutamate; HAND 5 HIV-associated neurocognitive disorders; ICV 5 intracranial volume; MI 5 myo-inositol; MRS 5 magnetic resonance spectroscopy; NAA 5 N-acetylaspartate; PBMC 5 peripheral blood mononuclear cell; PLSD 5 protected least significant difference; SN 5 seronegative; U-HIV 5 HIV1 infected subjects with undetectable peripheral blood mononuclear cells HIV DNA; VRS 5 Virchow-Robin spaces. Conclusion:

HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy

“…At the same time, associations of elevated CD14+ HIV DNA with decreased total and subcortical gray matter volumes indicate that HIV DNA, as well, may contribute to central atrophy. As our previous work did identify a significant association between lateral ventricular enlargement and elevated PBMC HIV DNA[13], we surmise that high plasma HIV RNA may mask relationships between HIV DNA and brain structure that are more apparent in treated HIV+ patients. Effects of viral load may contribute to the lack of associations between HIV DNA and volumes of basal ganglia and striatum.…”

“…[12, 13] However, the relationship between peripheral HIV DNA and brain structure has not been investigated in treatment-naïve subjects with HIV infection; nor have evaluations used HIV DNA isolated from CD14+ monocytes. In the Southeast Asia Research Collaboration with Hawaii (SEARCH) 001 Cohort Study, failure to eliminate HIV DNA in monocytes was associated with continued neurocognitive impairment more than three years after initiating cART.…”

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

“…[183] These preliminary observation warrant further studies on the differential efficacy of ARVs according to target cells: the repeated association between HIV reservoir size (measured as PBMC-or monocyte-associated quantitative HIV DNA) and HAND support the implementation of specific drug strategies in selected patients (those with low CD4+ cells nadir, high HIV RNA zenith and high cumulative viremia for instance). [184,185] …”

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

“…12 Detectable HIV DNA in the peripheral blood despite viral suppression is linked to smaller subcortical and cerebellar gray matter volumes. 13 …”