Influence of HAART on HIV-Related CNS Disease and Neuroinflammation

Anthony, Iain; Ramage, Stephen; Carnie, Frances W.; Simmonds, Peter; Bell, Jeanne E.

doi:10.1093/jnen/64.6.529

Cited by 258 publications

(195 citation statements)

References 31 publications

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“…100 Furthermore, the rate of HIVE at autopsy has remained constant or might even be increasing. 120 Thus, HAD continues to be an important cause of morbidity among HIVpositive patients also in the era of HAART, and significant cognitive impairment may persist within the limits of current treatment approaches. 11 McArthur and colleagues 11 suggest that HAD in the era of HAART may have three distinct subtypes: (1) a "subacute progressive" dementia in untreated patients similar to that seen in the pre-HAART era or in patients on HAART with high viral resistance; (2) a "chronic active" dementia in patients on HAART with poor adherence or with low viral resistance, and (3) a "chronic inactive" dementia in patients on HAART with good drug adherence and effective viral suppression.…”

Section: Antiretroviral Therapy: the Era Of Haartmentioning

confidence: 99%

HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

143

125

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Introduction HIV is a ribonucleic acid (RNA) retrovirus that is the causative agent for AIDS. HIV belongs to the Lentivirus genus in the family Retroviridae, characterized by a replication cycle in which the viral RNA is reverse transcribed into a DNA proviral form that is integrated into the host cell genome. The retrovirus is composed of two copies of single-stranded RNA that codes for the virus's 9 genes. The RNA is non-covalently linked to the core proteins, which in turn is surrounded by a viral envelope, which enables the virus to enter cells by binding to a specific cellular receptor located on the surface of cluster of differentiation 4 (CD4) cells. 1 A few years after the discovery of HIV-1, a second virus, HIV-2, was found in West Africa. HIV-1 and HIV-2 differ regarding their content of the genome, resulting in lower AIDS rates in HIV-2 infected individuals. 2 Once exposed to the body, the HIV virus antibodies may be detected after an acute flu-like illness, and then proceeds to infect specific cells of the immune system during an asymptomatic period that may last for years. In order to enter a cell, HIV must bind to CD4, typically found on T lymphocytes, blood monocytes, macrophages and some dendrite cells, and subsequently to one or a combination of several possible chemokine co-receptors, usually CCR5 and CXCR4. 3,4 The late HIV infection and psychiatric illness B Owe-Larsson, L Säll, E Salamon, C Allgulander Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry at Karolinska University Hospital Huddinge, Stockholm, Sweden Abstract Objective: To review the clinical features and current knowledge on the treatment of psychiatric symptoms and disorders in patients with human immunodeficiency virus (HIV) infection. Method: We searched the PubMed database combining HIV/AIDS with different keywords for psychiatric diagnoses and symptoms (e.g. depression, mania, anxiety, psychosis, dementia, substance abuse) and for psychopharmacological treatment. The years covered by these searches included 1980 to 2008. Results: Patients with HIV infection are at an increased risk of psychiatric illness. Major depressive disorder and subsyndromal depressive symptoms, as well as anxiety disorder and substance abuse are more prevalent among HIV infected individuals than among the general population. HIV-associated neurocognitive disorders (HAND) are common among HIV patients, and HIV-associated dementia (HAD) is a serious condition during the acquired immune deficiency syndrome (AIDS) stage of HIV disease. Secondary mania and psychosis might be the first clinical symptom of HIV dementia. The introduction of highly active anti-retroviral therapy (HAART) has resulted in significant decreases in morbidity and mortality for HIV infected patients. HAART has also decreased the incidence of HAD, but does not give complete protection from this condition. The utility of psychotropic medications in HIV patients has not been studied sufficiently as a basis for guidelines, and more controlled trials are n...

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Section: Antiretroviral Therapy: the Era Of Haartmentioning

confidence: 99%

HIV infection and psychiatric illness

Owe‐Larsson

Säll²,

Salamon³

et al. 2009

Afr. J. Psych

143

125

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“…Human immunodeficiency virus (HIV) enters the CNS early after infection and causes cognitive and motor impairment in 30 -60% of infected individuals (Anthony et al, 2005). The cellular basis and mechanisms by which HIV-1 induces neuropathogy, or NeuroAIDS, are still not well understood (Brack-Werner, 1999;Gonzalez-Scarano and Martin-Garcia, 2005).…”

Section: Introductionmentioning

confidence: 99%

Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes

Eugenín¹,

Berman²

2007

J. Neurosci.

118

172

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Human immunodeficiency virus (HIV) entry into the CNS is an early event after infection, resulting in neurological dysfunction in a significant number of individuals. As people with acquired immunodeficiency syndrome (AIDS) live longer, the prevalence of cognitive impairment is increasing, despite antiretroviral therapy. The mechanisms that mediate CNS dysfunction are still not completely understood, and include inflammation, viral presence, and/or replication. In this report, we characterize a novel role of gap junctions in transmitting and thereby amplifying toxic signals originating from HIV-infected astrocytes that trigger cell death in uninfected astrocytes. HIV-infected astrocytes were resistant to apoptosis; however, uninfected astrocytes forming gap junctions with infected astrocytes were apoptotic. Gap junction blockers abolished apoptosis in uninfected astrocytes, supporting the role of these channels in amplifying cell death. Our findings describe a novel mechanism of toxicity within the brain, triggered by low numbers of HIV-infected astrocytes and amplified by gap junctions, contributing to the pathogenesis of NeuroAIDS.

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“…Anthony and colleagues [97] found a high level of microglial/macrophage activation that is comparable with the levels seen, pre-HAART, in HIVE and AIDS cases. This result was maximal in the hippocampus where microglial/macrophage upregulation in the HAART-treated group exceeded that seen in HIVE.…”

Section: Aging Chronic Haart Administration and Development Of Cognimentioning

confidence: 53%

“…This may pose a threat for the future health of individuals maintained long-term on HAART therapy. [97]. Neuroinflamaton is also a feature of both aging and AD (for review see [98]).…”

Section: Aging Chronic Haart Administration and Development Of Cognimentioning

confidence: 99%

Development of 2′-Deoxy-4′-C-Ethynyl-2-Fluoroadenosine (EFdA) which has Supremely High Anti-HIV Activity and Low Toxicity and Prevents the Emergence of Resistant HIV Mutants, and Discovery of Different Substrate Selectivity between Viral and Human Nucleic Acid Polymerases

Ohrui¹

2013

J Antivir Antiretrovir

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Highly Active Antiretroviral Therapy (HAART) has significantly reduced AIDS-related morbidity and mortality. However the prevalence of HIV-1-Associated Neurocognitive Disorders (HAND) has been on the rise in the post-HAART era. A majority of the side effects of HAART can in part at least be attributed directly, or indirectly, to mitochondrial dysfunction. Indeed the rapid early clinical phase-in of HAART required dose de-escalations secondary to toxicities suggested to be related to drug side effects affecting mitochondria. Central to central nervous system (CNS) function is the amyloid precursor protein (APP), the parent protein from which amyloid-beta (Aβ) peptide is generated. Aβ generation and aggregation as plaques are well known in the age related dementia, Alzheimer's disease (AD). It has been demonstrated that Aβ is common feature of the HIV infected brain as well. Further, reactive oxygen species (ROS) production is upregulated by HAART. Importantly, ROS promote β-secretase expression; a mechanism by which HAART may promote cognitive dysfunction, even in immune-competent HIV infected individuals.

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Influence of HAART on HIV-Related CNS Disease and Neuroinflammation

Cited by 258 publications

References 31 publications

HIV infection and psychiatric illness

HIV infection and psychiatric illness

Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes

Development of 2′-Deoxy-4′-C-Ethynyl-2-Fluoroadenosine (EFdA) which has Supremely High Anti-HIV Activity and Low Toxicity and Prevents the Emergence of Resistant HIV Mutants, and Discovery of Different Substrate Selectivity between Viral and Human Nucleic Acid Polymerases

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