HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment
Deanna Saylor,Alex M. Dickens,Ned Sacktor,Norman J. Haughey,Barbara S. Slusher,Mikhail V. Pletnikov,Joseph L. Mankowski,Amanda Brown,David J. Volsky,Justin C. McArthur +9 more
903
TL;DR: It is suggested 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.
read more
Abstract: 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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
The NeuroinflammatoryPotential of HIV-1 NefVariants in Modulating the Gene Expression Profile of Astrocytes
TL;DR: The downregulation in cytokines and kynurenine metabolites observed after siRNA-Nef interference indicates the possibility of combining the RNA interference approach with current antiretroviral therapy to prevent neurotoxicity development.
Neuroinflammation driven by human immunodeficiency virus-1 (HIV-1) directs the expression of long noncoding RNA RP11-677M14.2 resulting in dysregulation of neurogranin in vivo and in vitro
Roberta S Dos Reis,Marc C. E. Wagner,Savannah McKenna,Velpandi Ayyavoo +3 more
TL;DR: This study characterized a newly identified long non-coding RNA (lncRNA) transcript (RP11-677M14.2), which is antisense to the NRGN locus and is highly expressed in the frontal cortex of HIV-1 individuals, and implicates a plausible role for lncRNA RP11-677M14.2 in modulating Nrgn expression that might serve as the mechanistic link between Nrgn loss and cognitive dysfunction in HAND.
3
A Novel Elvitegravir Nanoformulation for Drug Delivery Across the Blood-Brain Barrier to Suppress HIV-1 in Macrophages and Microglia
Yuqing Gong
- 01 Jan 2020
TL;DR: The central hypothesis was that the selected ARV, elvitegravir (EVG), in nanoformulation would have increased transmigration across the blood-brain barrier (BBB), as well as increased drug uptake in macrophages and microglia after crossing the BBB, leading to increased antiviral activity in Macrophage and micro glia, relative to the native drug.
The relationship between cognitive change and physical health and behavioural outcomes in a Ugandan cohort of adults living with HIV - a longitudinal study.
Georgina Spies,Christy A. Denckla,Sumaya Mall,Jonathan Levin,Soraya Seedat,Noeline Nakasujja,Eugene Kinyanda +6 more
TL;DR: This is the first study to investigate the longitudinal relationships between cognitive function and health outcomes among Ugandan adults living with HIV and provide insights into the possible links between Cognitive function and negative clinical and behavioural health outcomes in peopleliving with HIV.
3
Modulation of OPRM1 Alternative Splicing by Morphine and HIV-1 Nef.
Martina Donadoni,Wenfei Huang,Shadan S Yarandi,Tricia H. Burdo,Sulie L. Chang,Ilker Kudret Sariyer +5 more
TL;DR: In this article, the molecular impact of intravenous drug abuse in HIV neuropathogenesis was investigated, and it was shown that HIV-1 may alter MOR isoform expression with Nef protein by amplifying the rate of alternative splicing induced by morphine.
3
References
Initiation of antiretroviral therapy in early asymptomatic HIV infection
Sean Emery,Shweta Sharma,Gerd Fätkenheuer,Josep M. Llibre,Jean-Michel Moli,Paula Munderi,Robin Wood,Karin L. Klingman,Simon Collins,H. Clifford Lane,Andrew N. Phil,James D. Neaton +11 more
TL;DR: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+, but the risks of unscheduled hospital admissions were similar in the two groups.
Updated research nosology for HIV-associated neurocognitive disorders
Andrea Antinori,Gabriele Arendt,James T. Becker,Bruce J. Brew,Desiree Byrd,Mariana Cherner,David B. Clifford,Paola Cinque,Leon G. Epstein,K. Goodkin,Magnus Gisslén,Igor Grant,Robert K. Heaton,Jeymohan Joseph,Karen Marder,Camillo Marra,Justin C. McArthur,Michael Nunn,Richard W. Price,Lynn Pulliam,Kevin Robertson,Ned Sacktor,Victor Valcour,Valerie Wojna +23 more
TL;DR: This report reviews the collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neuroc cognitive impairment to categorize individuals with subclinical impairment.
Control of Viremia in Simian Immunodeficiency Virus Infection by CD8+ Lymphocytes
Jörn E. Schmitz,Marcelo J. Kuroda,Sampa Santra,Vito G. Sasseville,Meredith A. Simon,Michelle A. Lifton,Paul Racz,Klara Tenner-Racz,Margaret Dalesandro,Bernhard J. Scallon,John Ghrayeb,Meryl A. Forman,David C. Montefiori,E. Peter Rieber,Norman L. Letvin,Keith A. Reimann +15 more
TL;DR: The results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.
2.3K
HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study.
Robert K. Heaton,David B. Clifford,Donald Franklin,Steven Paul Woods,Christopher Ake,Florin Vaida,Ronald J. Ellis,S. Letendre,Thomas D. Marcotte,Joseph H. Atkinson,Monica Rivera-Mindt,Ofilio Vigil,Michael J. Taylor,Ann C. Collier,Camillo Marra,Benjamin B. Gelman,Justin C. McArthur,Susan Morgello,David M. Simpson,McCutchan Ja,Ian Abramson,Anthony Gamst,Christine Fennema-Notestine,Terry L. Jernigan,Joseph K. Wong,Igor Grant +25 more
TL;DR: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities.
HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors
Robert K. Heaton,Donald Franklin,Ronald J. Ellis,J. Allen McCutchan,Scott Letendre,Shannon LeBlanc,Stephanie Corkran,Nichole A. Duarte,David B. Clifford,Steven Paul Woods,Ann C. Collier,Christina M. Marra,Susan Morgello,Monica Rivera Mindt,Michael J. Taylor,Thomas D. Marcotte,J. Hampton Atkinson,Tanya Wolfson,Benjamin B. Gelman,Justin C. McArthur,David M. Simpson,Ian Abramson,Anthony Gamst,Christine Fennema-Notestine,Terry L. Jernigan,Joseph K. Wong,Igor Grant +26 more
TL;DR: In this article, the authors used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988-1995, N = 857) and CART era(2000-2007; N = 937).
Related Papers (5)
Robert K. Heaton,David B. Clifford,Donald Franklin,Steven Paul Woods,Christopher Ake,Florin Vaida,Ronald J. Ellis,S. Letendre,Thomas D. Marcotte,Joseph H. Atkinson,Monica Rivera-Mindt,Ofilio Vigil,Michael J. Taylor,Ann C. Collier,Camillo Marra,Benjamin B. Gelman,Justin C. McArthur,Susan Morgello,David M. Simpson,McCutchan Ja,Ian Abramson,Anthony Gamst,Christine Fennema-Notestine,Terry L. Jernigan,Joseph K. Wong,Igor Grant +25 more
Andrea Antinori,Gabriele Arendt,James T. Becker,Bruce J. Brew,Desiree Byrd,Mariana Cherner,David B. Clifford,Paola Cinque,Leon G. Epstein,K. Goodkin,Magnus Gisslén,Igor Grant,Robert K. Heaton,Jeymohan Joseph,Karen Marder,Camillo Marra,Justin C. McArthur,Michael Nunn,Richard W. Price,Lynn Pulliam,Kevin Robertson,Ned Sacktor,Victor Valcour,Valerie Wojna +23 more
Robert K. Heaton,Donald Franklin,Ronald J. Ellis,J. Allen McCutchan,Scott Letendre,Shannon LeBlanc,Stephanie Corkran,Nichole A. Duarte,David B. Clifford,Steven Paul Woods,Ann C. Collier,Christina M. Marra,Susan Morgello,Monica Rivera Mindt,Michael J. Taylor,Thomas D. Marcotte,J. Hampton Atkinson,Tanya Wolfson,Benjamin B. Gelman,Justin C. McArthur,David M. Simpson,Ian Abramson,Anthony Gamst,Christine Fennema-Notestine,Terry L. Jernigan,Joseph K. Wong,Igor Grant +26 more
David B. Clifford,Beau M. Ances +1 more