Journal of neurovirology
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Journal of neurovirology · Aug 2020
Multicenter StudyEvidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.
We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. ⋯ However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.
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Journal of neurovirology · Feb 2016
Randomized Controlled Trial Multicenter StudyPeripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.
Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. ⋯ In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.
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Journal of neurovirology · Jun 2014
Multicenter Study Observational StudyHIV-associated distal neuropathic pain is associated with smaller total cerebral cortical gray matter.
Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50 % of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. ⋯ The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r = -0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance.
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Journal of neurovirology · Jun 2014
Multicenter StudyPredictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART.
The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). ⋯ Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease.
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Journal of neurovirology · Jun 2013
Multicenter StudyProgressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy.
Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet, whether neurological injury can progress in this setting remains uncertain. Magnetic resonance spectroscopy and neurocognitive and clinical assessments were performed over 2 years in 226 HIV-infected individuals on stable CART, including 138 individuals who were neurocognitively asymptomatic (NA). ⋯ Neurocognitive decline was associated with longitudinal decreases in Glx in the FWM and the BG, and in NAA in the BG. Widespread progressive changes in the brain, including neuronal injury, occur in chronically HIV-infected persons despite stable antiretroviral treatment and virologic suppression and can lead to neurocognitive declines. The basis for these findings is poorly understood and warrants further study.