HIV, Antiretroviral Therapies, and the Brain

Liner, Kevin J.; Ro, Michelle J.; Robertson, Kevin

doi:10.1007/s11904-010-0042-8

Cited by 74 publications

(48 citation statements)

References 49 publications

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“…The continued presence of HAND despite cART could result from non-mutually-exclusive factors including irreversible injury prior to initiating cART, persistent HIV-1 RNA in the brain [7], antiretroviral treatment toxicities [8–10], and/or persistent low level inflammation [11]. Currently, the diagnosis of HAND requires neuropsychological performance (NP) testing and self-reported assessment of activities of daily living with the following classifications used: neuropsychologically normal, asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV associated dementia (HAD) [12].…”

Section: Introductionmentioning

confidence: 99%

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Ances

Hammoud

2014

Current Opinion in HIV and AIDS

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Purpose of review HIV enters the brain after initial infection, and with time can lead to HIV associated neurocognitive disorders (HAND). While the introduction of combination antiretroviral therapy (cART) has reduced the more severe forms of HAND, milder forms are still highly prevalent. The “gold standard” for HAND diagnosis remains detailed neuropsychological performance (NP) testing but additional biomarkers (including neuroimaging) may assist in early detection of HAND. Recent findings We review the application of recently developed non-invasive magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques in HIV+ individuals. In particular, magnetic resonance spectroscopy (MRS) may be more sensitive than conventional MRI alone in detecting HIV associated changes. Diffusion tensor imaging (DTI) has become increasingly popular for assessing changes in white matter structural integrity due to HIV. Both functional MRI and PET have been limitedly performed but could provide keys for characterizing neuropathophysiologic changes due to HIV. Summary It is hoped that continued progress will allow novel neuroimaging methods to be included in future HAND management guidelines.

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Section: Introductionmentioning

confidence: 99%

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Ances

Hammoud

2014

Current Opinion in HIV and AIDS

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“…Peptide therapeutics are generally not transported from the blood to the brain, failing to cross the brain capillary endothelial wall that makes up the blood-brain barrier (BBB) in vivo (40), and this lack of brain distribution has precluded potential benefits, for example, in the treatment of HIV-1 dementia and viral encephalitis (41). For HIV-1, the peptide fusion inhibitor enfuvirtide is used as a salvage therapy for multidrug-resistant HIV-1-infected patients; however, its clinical use is limited by a short half-life, poor biodistribution properties, and the parenteral route of delivery (39).…”

mentioning

confidence: 99%

Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides

Mathieu

Huey

Jurgens

et al. 2015

J Virol

100

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Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infection in vivo in animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS)and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.

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“…Prospective studies are needed to determine if early diagnosis and initiation of antiretroviral therapy would reduce the burden of NCI among HIV-infected persons. 26 A recent study showed that patients with early HIV infection had similar neurocognitive functioning compared to HIV-uninfected persons, suggesting that detrimental effects of HIV on the brain may not occur immediately, potentially providing an opportunity for early intervention. 27 Clinical trials are underway, including a substudy of the Strategic Timing of Antiretroviral Treatment (START) trial, examining neurocognitive functioning among those treated immediately compared to later in their disease course.…”

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confidence: 99%

Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons

et al. 2013

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Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV1) compared to HIV-negative controls.Methods: We performed a cross-sectional study among 200 HIV1 and 50 matched HIV-uninfected (HIV2) military beneficiaries. HIV1 patients were categorized as earlier (,6 years of HIV, no AIDSdefining conditions, and CD4 nadir .200 cells/mm 3 ) or later stage patients (n 5 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests.Results: HIV1 patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm 3 , and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm 3 ). NCI was diagnosed among 38 (19%, 95% confidence interval 14%-25%) HIV1 patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p 5 0.72). The prevalence of NCI among HIV1 patients was similar to HIV2 patients.Conclusions: HIV1 patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment.

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HIV, Antiretroviral Therapies, and the Brain

Cited by 74 publications

References 49 publications

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides

Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons

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