Role of neuroimaging in HIV-associated neurocognitive disorders.

Human immunodeficiency virus (HIV) enters the brain soon after seroconversion and can cause HIV-associated neurocognitive disorders (HAND). Although the more severe and progressive forms of HAND are less prevalent due to combination antiretroviral therapy (cART), ∼ 40% of HIV-infected (HIV+) patients continue to have cognitive impairment. Some HIV+ individuals who have effective plasma HIV-1 RNA suppression with cART still develop HAND. It is often difficult to diagnose HAND in the outpatient setting as detailed neuropsychological performance testing is required. Additional biomarkers that are relatively easy to obtain and clinically relevant are needed for assessing HIV-associated neuropathologic changes. Recently developed noninvasive magnetic resonance imaging (MRI) techniques have great potential to serve as biomarkers. The authors review the application of some of these neuroimaging techniques, magnetic resonance spectroscopy (MRS), volumetric MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), in HIV+ individuals. Each of the neuroimaging methods offers unique insight into mechanisms underlying neuroHIV, could monitor disease progression, and may assist in evaluating the efficacy of particular cART regimens. It is hoped that considerable progress will continue to occur such that some of these neuroimaging methods will be incorporated across multiple sites and included in future HAND guidelines.

Chronic HIV Infection and Aging: Application of a Geroscience-Guided Approach.

ABSTRACT: The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH.

Diabetes mellitus is associated with declines in physical function among men with and without HIV.

OBJECTIVE: To determine the longitudinal relationships between abnormal glucose metabolism and physical function in persons with HIV (PWH) and without HIV. DESIGN: Prospective cohort study of men with or at risk for HIV in four United States cities between 2006 and 2018. METHODS: Men with or at risk for HIV from the Multicenter AIDS Cohort Study (MACS) had semi-annual assessments of glycemic status, grip strength, and gait speed. We used linear mixed models with random intercept to assess associations between glycemic status and physical function. Glycemic status was categorized as normal, impaired fasting glucose (IFG), controlled diabetes mellitus [hemoglobin A1C (HbA1C) <7.5%], or uncontrolled diabetes mellitus (HbA1C ≥ 7.5%). RESULTS: Of 2240 men, 52% were PWH. Diabetes mellitus was similar among PWH (7.7%) vs. persons without HIV (6.7%, P = 0.36) at baseline. PWH had slower gait speed (1.17 vs. 1.20 m/s, P < 0.01) but similar grip strength (40.1 vs. 39.8 kg, P = 0.76) compared with persons without HIV at baseline. In multivariate models, gait speed decline was greater with controlled diabetes mellitus [-0.018 m/s (-0.032 to -0.005), P = 0.01] and grip strength decline was greater with controlled [-0.560 kg (-1.096 to -0.024), P = 0.04] and uncontrolled diabetes mellitus [-0.937 kg (-1.684 to -0.190), P = 0.01), regardless of HIV serostatus compared with normoglycemic individuals. DISCUSSION: Abnormal glucose metabolism was associated with declines in gait speed and grip strength regardless of HIV serostatus. These data suggest that improvement in glucose control should be investigated as an intervenable target to prevent progression of physical function limitations among PWH.

Impact of Coronavirus Disease 2019 on Infectious Diseases Fellows in the United States: Perspectives From the First National Infectious Diseases Fellows Call.

The coronavirus disease 2019 (COVID-19) pandemic has affected many providers, but its impact on Infectious Diseases (ID) fellows in the United States is largely undescribed. In this study, we discuss key issues that emerged from the first national ID Fellows Call with respect to the ID fellow's role during the COVID-19 pandemic, teaching/learning, and research.