Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 10/2013

01-10-2013 | Infection (J Berger, Section Editor)

Update on HIV-Associated Neurocognitive Disorders

Authors: Tariq B. Alfahad, Avindra Nath

Published in: Current Neurology and Neuroscience Reports | Issue 10/2013

Login to get access

Abstract

Neurocognitive disorders are a feared complication of HIV infection, especially in the post-antiretroviral era as patients are living longer. These disorders are challenging in terms of diagnosis and treatment. The clinical syndrome has evolved, driven in part by comorbidities such as aging, drug abuse, psychiatric illnesses, and a metabolic syndrome associated with the use of antiretroviral drugs. Additionally some individuals may develop a fulminant immune reconstitution syndrome. Hence, treatment of these patients needs to be individualized. The focus of research in the HIV field has recently switched towards elimination of the HIV reservoir as a means of combating long-term HIV complications. However, these approaches may be suitable for limited populations and might not be applicable once the HIV reservoir has been established in the brain. Further, all clinical trials using neuroprotective or anti-inflammatory drugs for treatment of HIV-associated neurocognitive disorders have been unsuccessful. Hence, neurological complications of HIV infection are the biggest challenge facing HIV researchers, and there is a critical need to develop new diagnostics and approaches for treatment of these disorders.
Literature
1.
2.
3.
•• Heaton RK, Franklin DR, Ellis RJ, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011;17:3–16. This study shows in a large multicenter cohort that the prevalence of HAND is still substantial despite adequate ART.PubMedCrossRef
4.
Carey CL, Woods SP, Rippeth JD, et al. Prospective memory in HIV-1 infection. J Clin Exp Neuropsychol. 2006;28(4):536–48.PubMedCrossRef
5.
Hinkin CH, Castellon SA, Durvasula RS, et al. Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity. Neurology. 2002;59(12):1944–50.PubMedCrossRef
6.
Cherner M, Masliah E, Ellis RJ, et al. Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis. Neurology. 2002;59:1563–7.PubMedCrossRef
7.
Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789–99.PubMedCrossRef
8.
Ellis R, Langford D, Masliah E. HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci. 2007;8(1):33–44.PubMedCrossRef
9.
McArthur JC, Brew BJ, Nath A. Neurological complications of HIV infection. Lancet Neurol. 2005;4(9):543–55.PubMedCrossRef
10.
Heaton RK, Franklin DR, Ellis RJ, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011;17(1):3–16.PubMedCrossRef
11.
• Johnson T, Nath A. Immune reconstitution inflammatory syndrome and the central nervous system. Curr Opin Neurol. 2011;24(3):284–90. This review discusses the clinical manifestations, pathophysiology, and management of IRIS affecting the CNS in HIV-infected individuals.PubMedCrossRef
12.
Gonzalez E, Rovin BH, Sen L, et al. HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci U S A. 2002;99:13795.PubMedCrossRef
13.
Valcour V, Shikuma C, Shiramizu B, et al. Age, apolipoprotein E4, and the risk of HIV dementia: the Hawaii Aging with HIV Cohort. J Neuroimmunol. 2004;157:197–202.PubMedCrossRef
14.
Singh KK, Ellis RJ, Marquie-Beck J, et al. CCR2 polymorphisms affect neuropsychological impairment in HIV-1-infected adults. J Neuroimmunol. 2004;157:185–92.PubMedCrossRef
15.
Mathers BM, Degenhardt L, Ali H, et al. HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage. Lancet. 2010;375:1014–28.PubMedCrossRef
16.
McCutchan JA, Marquie-Beck JA, Fitzsimons CA, et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology. 2012;78:485–92.PubMedCrossRef
17.
Valcour VG, Sacktor NC, Paul RH, et al. Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging with HIV Cohort. J Acquir Immune Defic Syndr. 2006;43:405–10.PubMedCrossRef
18.
McArthur JC, Hoover DR, Bacellar H, et al. Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS cohort study. Neurology. 1993;43:2245–52.PubMedCrossRef
19.
Becker JT, Kingsley L, Mullen J, et al. Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men. Neurology. 2009;73:1292–9.PubMedCrossRef
20.
Esiri MM, Biddolph SC, Morris CS. Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry. 1998;65:29–33.PubMedCrossRef
21.
Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS. 2005;19:127–35.PubMedCrossRef
22.
• Achim CL, Adame A, Dumaop W, et al. Increased accumulation of intraneuronal amyloid beta in HIV-infected patients. J Neuroimmune Pharmacol. 2009;4:190–9. This demonstrates that the amyloid based pathology in HIV infected individuals is distinctly different from that in Alzheimer’s disease.PubMedCrossRef
23.
Cherner M, Ellis RJ, Lazzaretto D, et al. Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS. 2004;18 Suppl 1:S27–34.PubMed
24.
Valcour V, Shikuma C, Shiramizu B, et al. Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology. 2004;63:822–7.PubMedCrossRef
25.
Sacktor N, Skolasky R, Selnes OA, et al. Neuropsychological test profile differences between young and old human immunodeficiency virus-positive individuals. J Neurovirol. 2007;13:203–9.PubMedCrossRef
26.
Parsons TD, Tucker KA, Hall CD, et al. Neurocognitive functioning and HAART in HIV and hepatitis C virus co-infection. AIDS. 2006;20:1591–5.PubMedCrossRef
27.
Tozzi V, Balestra P, Lorenzini P, et al. Prevalence and risk factors for human immunodeficiency virus-associated neurocognitive impairment, 1996 to 2002: results from an urban observational cohort. J Neurovirol. 2005;11:265–73.PubMedCrossRef
28.
Sun B, Abadjian L, Rempel H, et al. Differential cognitive impairment in HCV coinfected men with controlled HIV compared to HCV monoinfection. J Acquir Immune Defic Syndr. 2013;62:190–6.PubMedCrossRef
29.
•• Nath A, Clements JE. Eradication of HIV from the brain: reasons for pause. AIDS. 2011;25(5):577–80. This article discusses the challenges in the eradication of HIV from the brain.PubMedCrossRef
30.
Palmer S, Maldarelli F, Wiegand A, et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A. 2008;105:3879–84.PubMedCrossRef
31.
Maldarelli F, Palmer S, King MS, et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007;3:e46.PubMedCrossRef
32.
Nath A. Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis. 2002;186 Suppl 2:S193–8.PubMedCrossRef
33.
34.
Bruce-Keller AJ, Chauhan A, Dimayuga FO, et al. Synaptic transport of human immunodeficiency virus-Tat protein causes neurotoxicity and gliosis in rat brain. J Neurosci. 2003;23(23):8417–22.PubMed
35.
Wang T, Lee MH, Choi E, et al. Granzyme B-induced neurotoxicity is mediated via activation of PAR-1 receptor and Kv1. 3 channel. PLoS One. 2012;7(8):e43950.PubMedCrossRef
36.
Wang T, Allie R, Conant K, et al. Granzyme B mediates neurotoxicity through a G-protein-coupled receptor. FASEB J. 2006;20(8):1209–11.PubMedCrossRef
37.
Ancuta P, Kamat A, Kunstman KJ, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One. 2008;3(6):e2516.PubMedCrossRef
38.
Kamat A, Ancuta P, Blumberg RS, et al. Serological markers for inflammatory bowel disease in AIDS patients with evidence of microbial translocation. PLoS One. 2010;5(11):e15533.PubMedCrossRef
39.
Dohgu S, Fleegal-DeMotta MA, Banks WA. Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by luminal microvessel IL-6 and GM-CSF. J Neuroinflammation. 2011;8(1):167.PubMedCrossRef
40.
Pang S, Koyanagi Y, Miles S, et al. High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature. 1990;343(6253):85–9.PubMedCrossRef
41.
Wu Y, Marsh JW. Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA. Science. 2001;293(5534):1503–6.PubMedCrossRef
42.
Teo I, Veryard C, Barnes H, et al. Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS. J Virol. 1997;71(4):2928–33.PubMed
43.
Marra CM, Zhao Y, Clifford DB, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS. 2009;23(11):1359–66.PubMedCrossRef
44.
Gray LR, Gabuzda D, Cowley D, et al. CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates. J Neurovirol. 2011;17(1):82–91.PubMedCrossRef
45.
Dunfee RL, Thomas ER, Gorry PR, et al. The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia. Proc Natl Acad Sci U S A. 2006;103(41):15160–5.PubMedCrossRef
46.
Gonzalez-Perez MP, O'Connell O, Lin R, et al. Independent evolution of macrophage-tropism and increased charge between HIV-1 R5 envelopes present in brain and immune tissue. Retrovirology. 2012;9:20.PubMedCrossRef
47.
Cowley D, Gray LR, Wesselingh SL, et al. Genetic and functional heterogeneity of CNS-derived tat alleles from patients with HIV-associated dementia. J Neurovirol. 2011;17(1):70–81.PubMedCrossRef
48.
Li W, Huang Y, Reid R, et al. NMDA receptor activation by HIV-Tat protein is clade dependent. J Neurosci. 2008;28(47):12190–8.PubMedCrossRef
49.
Olivieri KC, Agopian KA, Mukerji J, et al. Evidence for adaptive evolution at the divergence between lymphoid and brain HIV-1 nef genes. AIDS Res Hum Retrovir. 2010;26(4):495–500.PubMedCrossRef
50.
Thompson KA, Churchill MJ, Gorry PR, et al. Astrocyte specific viral strains in HIV dementia. Ann Neurol. 2004;56(6):873–7.PubMedCrossRef
51.
Lamers SL, Gray RR, Salemi M, et al. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues. Infect Genet Evol. 2011;11(1):31–7.PubMedCrossRef
52.
Vissers M, Stelma FF, Koopmans PP. Could differential virological characteristics account for ongoing viral replication and insidious damage of the brain during HIV 1 infection of the central nervous system? J Clin Virol. 2010;49(4):231–8.PubMedCrossRef
53.
Lamers SL, Salemi M, Galligan DC, et al. Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain. J Neurovirol. 2010;16(3):230–41.PubMedCrossRef
54.
Aquaro S, Calio R, Balzarini J, et al. Macrophages and HIV infection: therapeutical approaches toward this strategic virus reservoir. Antiviral Res. 2002;55(2):209–25.PubMedCrossRef
55.
Cinque P, Presi S, Bestetti A, et al. Effect of genotypic resistance on the virological response to highly active antiretroviral therapy in cerebrospinal fluid. AIDS Res Hum Retrovir. 2001;17(5):377–83.PubMedCrossRef
56.
Letendre SL, Ellis RJ, Ances BM, McCutchan JA. Neurologic complications of HIV disease and their treatment. Top HIV Med. 2010;18(2):45–55.PubMed
57.
• Cohen J. Understanding HIV latency to undo it. Science. 2011;332(6031):786. This reviews all the ongoing clinical trials for eradication of HIV infection.PubMedCrossRef
58.
Johnson T, Nath A. Immune reconstitution inflammatory syndrome and the central nervous system. Curr Opin Neurol. 2011;24(3):284–90.PubMedCrossRef
59.
Holt N, Wang J, Kim K, et al. Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat Biotechnol. 2010;28(8):839–47.PubMedCrossRef
60.
Ene L, Duiculescu D, Ruta SM. How much do antiretroviral drugs penetrate into the central nervous system? J Med Life. 2011;4(4):432.PubMed
61.
Sawchuk RJ, Yang Z. Investigation of distribution, transport and uptake of anti-HIV drugs to the central nervous system. Adv Drug Deliv Rev. 1999;39(1):5–31.PubMedCrossRef
62.
Croteau D, Letendre S, Best BM, et al. Total raltegravir concentrations in cerebrospinal fluid exceed the 50-percent inhibitory concentration for wild-type HIV-1. Antimicrob Agents Chemother. 2010;54(12):5156–60.PubMedCrossRef
63.
Dahl V, Lee E, Peterson J, et al. Raltegravir treatment intensification does not alter cerebrospinal fluid HIV-1 infection or immunoactivation in subjects on suppressive therapy. J Infect Dis. 2011;204(12):1936–45.PubMedCrossRef
64.
Nowacek A, Gendelman HE. NanoART, neuroAIDS and CNS drug delivery. Nanomedicine. 2009;4(5):557–74.PubMedCrossRef
65.
Rao KS, Reddy MK, Horning JL. TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs. Biomaterials. 2008;29(33):4429–38.PubMedCrossRef
66.
Metadata
Title
Update on HIV-Associated Neurocognitive Disorders
Authors
Tariq B. Alfahad
Avindra Nath
Publication date
01-10-2013
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 10/2013
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-013-0387-7

Other articles of this Issue 10/2013

Current Neurology and Neuroscience Reports 10/2013 Go to the issue

Infection (J Berger, Section Editor)

Neurologic Complications of Infective Endocarditis

Genetics (V Bonifati, Section Editor)

Episodic Movement Disorders: From Phenotype to Genotype and Back

Neuroimaging (DJ Brooks, Section Editor)

The Functional Anatomy of Impulse Control Disorders

Dementia (KS Marder, Section Editor)

Genome-wide Association Studies in Alzheimer’s Disease: A Review

Invited Commentary

Medication Nonadherence in Parkinson’s Disease

Neuroimaging (DJ Brooks, Section Editor)

Imaging the Role of GABA in Movement Disorders