Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

Ferretti, Francesca; Gisslén, Magnus; Cinque, Paola; Price, Richard W.

doi:10.1007/s11904-015-0267-7

Cited by 93 publications

(99 citation statements)

References 71 publications

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“…These presentations have included neurocognitive disorders, behavioral changes, fatigue, headache, cerebellar dysfunction, and focal motor or sensory symptoms. 6 Visualized radiographic abnormalities are typically similar to our case presentation, with diffuse T2-weighted hyperintensities involving the white matter, cerebellum, basal ganglia, and periventricular parenchyma. Awareness of this condition and clinical suspicion of HIV CNS infection despite antiretroviral therapy and viral suppression is the key to diagnosis and management.…”

supporting

confidence: 73%

“…HIV CSF viral escape syndrome is a rare manifestation of HIV infection in patients who are actively on antiretroviral therapy with discordance between plasma and CSF viral load. 5,6 The pathophysiologic mechanism is not fully understood, but it has been proposed that a distinct HIV clonality with resistance to the antiretroviral regimen evolves in the CSF compartment after initial infection or by the failure to achieve therapeutic concentrations in the CNS.…”

Section: Sectionmentioning

confidence: 99%

“…Treatment is contingent upon HIV RNA resistance testing from the CSF compartment and changes of the antiretroviral therapy incorporating agents with higher CNS penetration capable of overcoming the resistance profile of the CSF HIV population. 6 There are no expert consensus recommendations regarding routine CSF screening for HIV viral load. It is reasonable to reserve CSF HIV RNA and genotype resistance testing only for cases where CSF viral escape syndrome is suspected and alternative diagnoses have been evaluated.…”

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confidence: 99%

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Clinical Reasoning: A 46-year-old man with persistent hiccups, cognitive dysfunction, and imbalance

et al. 2017

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A 46-year-old, right-handed, African American man presented to the emergency department after 1 week of persistent hiccups and 3 days of nausea and vomiting. His family member also noted that he had been experiencing right-hand tremor and gait imbalance for the last 3 months. Over the 6 months prior to presentation, the patient's coworkers had noticed that he was completing his work more slowly, that he was forgetting how to perform simple tasks, and that several times he had come to work at the wrong hours. The patient had a history of HIV diagnosed 10 years earlier and reported good adherence to an antiretroviral regimen consisting of tenofovir, emtricitabine, and atazanavir boosted by ritonavir, without any changes for several years. His viral load was undetectable when tested 8 months prior to presentation.The patient had experienced a 9-kg (20-lb) weight loss over the last 6 months and watery, nonbloody diarrhea for 3 days. He denied illicit or IV drug use, new sexual partners, recent travel, ill contacts, or toxic exposures.Neurologic examination revealed frequent hiccups; decreased short-term recall (1 of 5 words) after 5 minutes with normal registration; a 4-6 Hz, lowamplitude postural and action tremor of the right hand; appendicular ataxia of the upper limbs; and gait ataxia, especially prominent with tandem gait. The remainder of the physical examination was normal.Questions for consideration:1. Based upon the patient's history and neurologic examination, where do each of the patient's symptoms and signs localize? 2. Which are the most common neurologic causes of persistent or intractable hiccups? 3. What medications can be used for symptomatic treatments of persistent hiccups? GO TO SECTION 2From the The patient's history and examination revealed executive dysfunction localizing to the frontal lobe and decreased recall localizing to the temporal lobe, both signs of cognitive dysfunction. The tremor of the right hand could localize to the left basal ganglia, the spinocerebellar tracts, or the rubrocerebellothalamic projections (Holmes rubral tremor). With the addition of cerebellar findings such as appendicular ataxia localizing to the lateral cerebellum, and gait ataxia localizing to the midline cerebellum, a cerebellar tremor is favored. However, rubral and cerebellar tremors can be difficult to distinguish because they have similar frequency and are present with action and at rest. The varying localizations should indicate to the clinician that this disease process is either multifocal or diffuse, rather than the result of a single, focal lesion. Hiccups, also called singultus, are paroxysmal myoclonic activations of the diaphragm involving a reflex arc with afferent vagal input, central integration in the medulla area postrema, and efferent output via the phrenic nerves.1 Ischemia, encephalitis, neuromyelitis optica, 2 or neoplastic lesions affecting the medullary integrating center including the area postrema are the most common primary neurologic causes, although many other causes have been de...

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Section: Sectionmentioning

confidence: 99%

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Clinical Reasoning: A 46-year-old man with persistent hiccups, cognitive dysfunction, and imbalance

et al. 2017

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“…Clinically, these patients tend to present with progressive cognitive decline, behavioural changes, ataxia, apraxia and focal deficits 38. Occasionally, they can present acutely with encephalopathy and seizures.…”

Section: Unusual Presentations Of Infectious Encephalitis (Chameleons)mentioning

confidence: 99%

“…Occasionally, they can present acutely with encephalopathy and seizures. MR scan of brain shows fairly symmetrical signal abnormalities in the cerebral, brain stem and cerebellar white matter with or without enhancement 38. CSF can be normal or show mildly elevated protein and white blood cell counts.…”

Section: Unusual Presentations Of Infectious Encephalitis (Chameleons)mentioning

confidence: 99%

Infectious encephalitis: mimics and chameleons

Toledano

Davies

2019

Pract Neurol

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Click here to listen to the Podcast ‘Query encephalitis’ is a common neurological consultation in hospitalised patients. Identifying the syndrome is only part of the puzzle. Although historically encephalitis has been almost synonymous with infection, we increasingly recognise parainfectious or postinfectious as well as other immune-mediated causes. We must also distinguish encephalitis from other causes of encephalopathy, including systemic infection, metabolic derangements, toxins, inherited metabolic disorders, hypoxia, trauma and vasculopathies. Here, we review the most important differential diagnoses (mimics) of patients presenting with an encephalitic syndrome and highlight some unusual presentations (chameleons) of infectious encephalitis.

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HIV and the Nervous System

Mina¹,

Smith²,

Nath³

2020

Encyclopedia of Life Sciences

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Human immunodeficiency virus (HIV) infection in the pre‐antiretroviral drug era was known to cause a variety of neurological syndromes, including HIV‐associated dementia, myelopathy, peripheral neuropathy, opportunistic infections of the nervous system and primary central nervous system (CNS) lymphoma. The era of efficient combined antiretroviral treatment has led to a shift in the nature of these syndromes, yet HIV infection is still a major cause of neurological disease, typically causing a more chronic effect, as is the case in mild cognitive impairment attributed to the virus. The mechanisms underlying this chronic effect are related to the CNS being a viral reservoir, as HIV does not directly infect neurons but does reside in different cells of the nervous system such as macrophages, microglia and astrocytes, implicating neuronal injury using neurotoxic viral factors and initiating processes of neuroinflammation and neurodegeneration. In addition, the antiretroviral treatment itself is responsible for some aspects of neurological morbidity, mainly peripheral neuropathy and possible CNS manifestations of immune reconstitution inflammatory syndrome after treatment is initiated. Key Concepts HIV‐1 invades the nervous system during early infection, frequently infecting perivascular macrophages, microglia and astrocytes. The central nervous system is a potential reservoir for HIV‐1, challenging eradication and leading to chronic neurological complications despite antiretroviral treatment. Neurotoxic viral factors, neuroinflammation and neurodegeneration are the main mechanisms underlying neuropathogenesis of HIV‐1. The main neurotoxic viral proteins are gp120, transactivator of transcription (Tat), Vpr and Nef. CNS‐infiltrating monocytes are the primary blood‐derived contributors to neuroinflammation in HIV infection, leading to gliosis and astrocytosis and the release of inflammatory cytokines such as TNF‐α, IL‐1β and interferons. Neurodegeneration has been shown to be mediated by DNA damage and mitochondrial abnormalities but also by other processes including protein aggregates, cellular senescence and epigenetic alterations. The major neurological syndrome seen in cases of treated HIV infection is mild neurocognitive impairment. In untreated patients, opportunistic infections, HIV‐myelopathy and primary CNS lymphoma and are the main causes of neurological disease. Antiretroviral treatment can also lead to a neurological sequela, whether due to direct neurological side effects of drugs or due to the indirect consequences of immune reconstitution inflammatory syndrome (IRIS).

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Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

Cited by 93 publications

References 71 publications

Clinical Reasoning: A 46-year-old man with persistent hiccups, cognitive dysfunction, and imbalance

Clinical Reasoning: A 46-year-old man with persistent hiccups, cognitive dysfunction, and imbalance

Infectious encephalitis: mimics and chameleons

HIV and the Nervous System

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