Human Immunodeficiency Virus-Associated Dementia

McArthur, Justin C.; Sacktor, Ned; Selnes, Ola A.

doi:10.1055/s-2008-1040831

Cited by 127 publications

(82 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CXCL10, a chemokine that specifically acts upon activated T cells and macrophages has been found to be closely associated with the progression of HIV-1-related CNS infection and neuropyschiatric impairment (3,8,9). Macrophages or microglia, but not neurons, are the predominant CNS reservoirs for the virus (43,46,47). Furthermore, the number of activated macrophages/microglia in the CNS correlate with HAD (48,49,50).…”

Section: Discussionmentioning

confidence: 99%

PDGF Synergistically Enhances IFN-γ-Induced Expression of CXCL10 in Blood-Derived Macrophages: Implications for HIV Dementia

Dhillon

Peng

Ransohoff

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

There is increasing cumulative evidence that activated mononuclear phagocytes (macrophages/microglia) releasing inflammatory mediators in the CNS are a better correlate of HIV-associated dementia (HAD) than the actual viral load in the brain. Earlier studies on simian HIV/rhesus macaque model of NeuroAIDS confirmed that pathological changes in brains of macaques with encephalitis were associated with up-regulation of platelet-derived growth factor (PDGF) and the chemokine, CXCL10. Because the complex interplay of inflammatory mediators released by macrophages often leads to the induction of neurotoxins in HAD, we hypothesized that PDGF could interact with IFN-γ to modulate the expression of CXCL10 in these primary virus target cells. Although PDGF alone had no effect on the induction of CXCL10 in human macrophages, in conjunction with IFN-γ, it significantly augmented the expression of CXCL10 RNA & protein through transcriptional and posttranscriptional mechanisms. Signaling molecules, such as JAK and STATs, PI3K, MAPK, and NF-κB were found to play a role in the synergistic induction of CXCL10. Furthermore, PDGF via its activation of p38 MAPK was able to increase the stability of IFN-γ-induced CXCL10 mRNA. Understanding the mechanisms involved in the synergistic up-regulation of CXCL10 could aid in the development of therapeutic modalities for HAD.

show abstract

Section: Discussionmentioning

confidence: 99%

PDGF Synergistically Enhances IFN-γ-Induced Expression of CXCL10 in Blood-Derived Macrophages: Implications for HIV Dementia

Dhillon

Peng

Ransohoff

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Therefore, HIV-1-infected individuals develop a range of cognitive symptoms, motor disturbances, behavioral changes, reduced concentration, headache, and peripheral neuropathies, which are collectively known as HIV-associated dementia (12,55). Before the advent of highly active antiretroviral therapy (HAART), ϳ20 -30% of individuals infected with HIV-1 developed HIV-associated dementia (56), and despite the clinical and immunological improvement of patients treated with HAART, the occurrence of HIV-1-related neuropathology in postmortem tissue has not changed (57). Because the antiviral drugs used in HAART have limited access to the brain, it is likely that the current antiviral therapy reduces the neurological symptoms by indirect means such as the reduction of peripheral viremia and the low occurrence of opportunistic infections due to the partial reconstitution of the immune response.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of HIV-1 Inhibition by the Lipid Mediator N-Arachidonoyldopamine

Sancho

Vega

Macho

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Several linear fatty acid dopamides (N-acyldopamines) have been identified recently in the brain. Among them, N-arachidonoyldopamine (NADA) is an endogenous lipid mediator sharing endocannabinoid and endovanilloid biological activities. We have reported previously that NADA exerts some of its biological activities through inhibition of the NF-κB pathway and, because this transcription factor plays a key role in HIV-1-long terminal repeat (LTR) trans activation, we have evaluated the anti-HIV-1 activity of NADA. In this study, we show that NADA inhibits vesicular stomatitis virus-pseudotyped HIV-1 infection in the human leukemia T cell line Jurkat, in primary T cells, and in the human astrocytic cell line U373-MG. Other endocannabinoids such as anandamide, 2-arachidonoylglycerol, and noladin ether did not show inhibitory activity in the HIV-1 replication assays. The anti-HIV-1 activity of NADA was independent of known cannabinoid and vanilloid receptor activation. In addition, NADA did not affect reverse transcription and integration steps of the viral cycle, and its inhibitory effect was additive with that of the reverse transcriptase inhibitor azidothymidine. NADA inhibited both TNF-α and HIV-1 trans activator protein-induced HIV-1-LTR activation. We also show that NADA counteracts the TNF-α-mediated trans activation capacity of the p65 NF-κB subunit without affecting its physical association to the HIV-1-LTR promoter. Moreover, NADA inhibited the p65 transcriptional activity by specifically targeting the phosphorylation of this NF-κB subunit at Ser536. These findings provide new mechanistic insights into the biological activities of NADA, and highlight the potential of lipid mediators for the management of AIDS.

show abstract

“…Moreover, history of substance abuse, head injury, cerebral vascular accident, or aging can also contribute to the development of neuropsychiatric impairment in HIV-infected patients. 41 Distinguishing the etiology of neuropsychiatric manifestations in HIV-infected patients in order to ensure the most optimal therapeutic approach is crucially important.…”

Section: Neuropsychiatric Complications Of Hiv and Artmentioning

confidence: 99%

Neuropsychiatric effects of tenofovir in comparison with other antiretroviral drugs

Ferrer¹,

Rakhmanina²

2013

NBHIV

View full text Add to dashboard Cite

Abstract:Tenofovir is a widely used antiretroviral medication indicated to treat adults and children infected with HIV. Current guidelines for the management of HIV infection recommend tenofovir disoproxil fumarate (TDF) as a component of the preferred first-line combination antiretroviral therapy. The efficacy, tolerability, prolonged half-life allowing for once-daily administration, and availability as a component of several fixed-dose formulations make TDF an attractive choice for treatment-naive and treatment-experienced HIV-infected patients. TDF is also widely used as a component of postexposure prophylaxis in noninfected individuals. Most importantly, it has been recently approved for use as pre-exposure prophylaxis for noninfected adults and adolescents to reduce the risk of HIV transmission. With increasing use of TDF among adults and children, understanding of the potential for drug-associated side effects is important. This review focuses on the neuropsychiatric effects of tenofovir in adults and children with HIV infection in comparison with other antiretroviral drugs.

show abstract

Human Immunodeficiency Virus-Associated Dementia

Cited by 127 publications

References 26 publications

PDGF Synergistically Enhances IFN-γ-Induced Expression of CXCL10 in Blood-Derived Macrophages: Implications for HIV Dementia

PDGF Synergistically Enhances IFN-γ-Induced Expression of CXCL10 in Blood-Derived Macrophages: Implications for HIV Dementia

Mechanisms of HIV-1 Inhibition by the Lipid Mediator N-Arachidonoyldopamine

Neuropsychiatric effects of tenofovir in comparison with other antiretroviral drugs

Contact Info

Product

Resources

About