Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China

Lin, Yuan; Qiao, Li; Wei, Feili; Ju, Youlun; Liu, Lifeng; Ji, Yaying; Smith, Davey M.; Li, Ning; Chen, Dexi

doi:10.1007/s13365-013-0150-5

Cited by 91 publications

(87 citation statements)

References 26 publications

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“…In individuals who develop ANI and MND, markers of immune 65–67 and cytokine activation 68,69 are more pronounced than in HIV+ individuals without cognitive impairment. Likewise, changes in bioenergetics, as measured with neuroimaging 70–72 and metabolomic appraches 73,74 , are readily apparent in individuals with ANI or MND compared with cognitively normal HIV+ individuals, as are accumulations of bioactive lipids, such as ceramide, and sterol markers of cell stress 75,76 .…”

Section: Biomarkers In Handmentioning

confidence: 97%

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

et al. 2016

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In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies -treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism -are needed to reverse or improve HAND-related neurological dysfunction. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Neurol. Author manuscript; available in PMC 2016 July 08. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript chronic infection that can be managed, is associated with a near-normal lifespan and in which opportunistic infections are rare 1 .The first major advancement was an understanding of the direct relationship between HIV replication and subsequent immunological and clinical progression. This finding emphasized the need to completely suppress HIV replication in order to control disease progression.The second major advancement was the development and deployment of combination antiretroviral therapy (CART), which can provide effective systemic suppression of HIV replication. The introduction of CART in the mid-1990s resulted in a 50% decline in the rate of death from AIDS, substantial decreases in rates of maternal-infant transmission, reduced incidence of opportunistic infections, and a 40-50% decrease in the incidence of HIVassociated dementia (HAD), which was previously common and is the most severe form of cognitive impairment associated with the infection 2 .The third major change in the care of HIV+ patients was the ability to monitor the efficacy of CART through the reliable and widespread measurement of CD4 + helper T cells, plasma HIV RNA levels and antiretroviral resistance profiles, all of which are now fully integrated into routine clinical care in the developed world and used to optimize treatment for individual patients. Plasma viral l...

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Section: Biomarkers In Handmentioning

confidence: 97%

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

et al. 2016

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“…Both MIP-1α and IL-8 are markers of inflammation in HIV infection and IL-8 has specifically been associated with ongoing inflammation in HIV+ individuals on HAART (Pierdominici, Giovannetti et al 2002; Letendre, Zheng et al 2011; Bastard, Soulie et al 2012; Mamik and Ghorpade 2014; Wada, Jacobson et al 2015). Additionally, CSF IL-8 correlates with HIV-associated neurocognitive disorders (Kamat, Lyons et al 2012; Yuan, Qiao et al 2013; Yuan, Liu et al 2015). …”

Section: Resultsmentioning

confidence: 99%

Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

2016

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HIV-1 associated neurocognitive disorders (HAND) remains a persistent problem despite antiretroviral therapy (ART), largely a result of continued inflammation in the periphery and the brain and neurotoxin release from activated myeloid cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection, play a central role the pathogenesis of HAND, and have parallels with monocyte-dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG-CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties that contribute to their benefit in atherosclerosis beyond lipid lowering. Here we investigated whether statins would modulate the monocyte phenotype and function associated with HIV-1 neuropathogenesis. Treatment ex vivo with simvastatin and atorvastatin reduced the proportion of CD16+ monocytes in peripheral blood mononuclear cells, as well as in purified monocytes, especially CD14++CD16+ ‘intermediate’ monocytes most closely associated with neurocognitive disease. Statin treatment also markedly reduced expression of CD163, which is also linked to HAND pathogenesis. Finally, simvastatin inhibited production of MCP-1 and other inflammatory cytokines following LPS stimulation, and reduced monocyte chemotaxis in response to MCP-1, a major driver of myeloid cell accumulation in the CNS in HAND. Together these findings suggest that statin drugs may be useful to prevent or reduce HAND in HIV-1 infected subjects on ART with persistent monocyte activation and inflammation.

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“…A separate study of individuals off cART identified increased inflammatory CSF IL-8, MCP-1, G-CSF, and IP-10 among those with cognitive impairment. (24…”

Section: Hand Pathophysiologymentioning

confidence: 99%

Interactions between ageing and NeuroAIDS

Hellmuth

Milanini

Valcour

2014

Current Opinion in HIV and AIDS

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Purpose of review To summarize recent advances in aging and neuroAIDS by reviewing relevant articles from the preceding eighteen months from PubMed and PsycINFO databases. Recent findings The success of combination antiretroviral therapy (cART) has led to aging of the HIV-infected population, which in turn contributes to the prevalence of HIV-associated neurocognitive disorder (HAND). Biomedical advances continue to clarify the pathophysiology of HAND despite effective cART, including chronic inflammatory and neurovascular etiologies. In recent months, associations between HAND and non-neurological medical diseases have been identified, as well as linkage to neuroimaging in those aging with HIV. Developing effective screening tools to detect impairment remains an important scientific gap, while promoting factors associated with successful cognitive aging is emerging as a possible means of enhancing quality of life. Summary A greater understanding of HAND pathophysiology among treated subjects with suppressed virus will aid in explaining the high prevalence of HAND despite effective cART and allow for development of novel targeted interventions. Neuroimaging and other biomarkers show promise in discerning HAND from age-associated cognitive disorders. Effective screening tools remain critically needed. Together, this work will inform promising strategies needed to address issues pertinent to an expanding group of older patients living with HIV.

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Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China

Cited by 91 publications

References 26 publications

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

Interactions between ageing and NeuroAIDS

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