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 HIV/AIDS Reports
Published in: Current HIV/AIDS Reports 2/2010

01-05-2010

HIV, Antiretroviral Therapies, and the Brain

Authors: Kevin J. Liner II, Michelle J. Ro, Kevin R. Robertson

Published in: Current HIV/AIDS Reports | Issue 2/2010

Login to get access

Abstract

While combination antiretroviral therapy (CART) has decreased the incidence of HIV-associated dementia, the severest form of HIV-associated neurocognitive disorders (HAND), mild neurocognitive disorder and asymptomatic neurocognitive impairment continue to persist, and there is evidence that neurocognitive deficits present even in acute HIV infection. Recent studies demonstrate that CART regimens with higher central nervous system (CNS) penetration effectiveness ranks may improve neurocognitive functioning. Considering these factors, earlier treatment initiation may be considered to protect the CNS. The functional impact of HAND on daily activities should be monitored. Areas that need further research are potential neurotoxicity of antiretrovirals, the eradication of potential latent reservoirs in the brain, when to start treatment to protect the CNS, and the neurological impact of HIV on the CNS in acute infection.
Literature
1.
Antinori A, Arendt G, Becker JT, et al.: Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007, 69:1789–1799.CrossRefPubMed
2.
Robertson KR, Smurzynski M, Parsons TD, et al.: The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 2007, 21:1915–1921.CrossRefPubMed
3.
•• Ellis R: Effects of CNS antiretroviral distribution on neurocognitive impairment in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) Study. In 134th Annual Meeting of the American Neurolological Association. Baltimore, MD; October 11–14, 2009. The ACTG ALLRT study yields evidence that higher-ranking CPE regimens correlate with neurocognitive improvement.
4.
Sterne JA, May M, Costagliola D, et al.: Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009, 373:1352–1363.CrossRefPubMed
5.
Tozzi V, Balestra P, Salvatori MF, et al.: Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 2009, 52:56–63.CrossRefPubMed
6.
Marra CM, Zhao Y, Clifford DB, et al.: Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009, 23:1359–1366.CrossRefPubMed
7.
• Robertson K, Zhaohui, S, Margolis, DM, et al.: Neurocognitive effects of treatment interruption in stable HIV + patients in an observational cohort: ACTG 5170. Neurology 2010, In press. The ACTG 5170 study found that patients discontinuing HAART experienced NP improvement, raising the possibility that ART may have neurotoxic effects.
8.
•• Letendre S: Revised CNS penetration-effectiveness ranks. In 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA; 2010. The updated CPE rankings divide ART drugs into four categories of penetration: high, high-intermediate, low-intermediate, and low.
9.
Patel K, Ming X, Williams PL, et al.: Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AIDS 2009, 23:1893–1901.CrossRefPubMed
10.
Letendre S, Marquie-Beck J, Capparelli E, et al.: Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008, 65:65–70.CrossRefPubMed
11.
Cysique LA, Vaida F, Letendre S, et al.: Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology 2009, 73:342–348.CrossRefPubMed
12.
Dickinson L, Khoo S, Back D: Pharmacokinetics and drug-drug interactions of antiretrovirals: an update. Antiviral Res 2009, 85:176–189.CrossRefPubMed
13.
Yilmaz A, Gisslen M, Spudich S, et al.: Raltegravir cerebrospinal fluid concentrations in HIV-1 infection. PLoS One 2009, 4:e6877.CrossRefPubMed
14.
Yilmaz A, Izadkhashti A, Price RW, et al.: Darunavir concentrations in cerebrospinal fluid and blood in HIV-1-infected individuals. AIDS Res Hum Retroviruses 2009, 25:457–461.CrossRefPubMed
15.
Yilmaz A, Watson V, Else L, Gisslen M: Cerebrospinal fluid maraviroc concentrations in HIV-1 infected patients. AIDS 2009, 23:2537–2540.CrossRefPubMed
16.
Walker DK, Bowers SJ, Mitchell RJ, et al.: Preclinical assessment of the distribution of maraviroc to potential human immunodeficiency virus (HIV) sanctuary sites in the central nervous system (CNS) and gut-associated lymphoid tissue (GALT). Xenobiotica 2008, 38:1330–1339.CrossRefPubMed
17.
Hanson LR, Frey WH 2nd: Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS. J Neuroimmune Pharmacol 2007, 2:81–86.CrossRefPubMed
18.
Polianova MT, Ruscetti FW, Pert CB, et al.: Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA). Peptides 2003, 24:1093–1098.CrossRefPubMed
19.
Nowacek A, Gendelman HE: NanoART, neuroAIDS and CNS drug delivery. Nanomed 2009, 4:557–574.CrossRef
20.
Chattopadhyay N, Zastre J, Wong HL, et al.: Solid lipid nanoparticles enhance the delivery of the HIV protease inhibitor, atazanavir, by a human brain endothelial cell line. Pharm Res 2008, 25:2262–2271.CrossRefPubMed
21.
Kuo YC, Chen HH: Entrapment and release of saquinavir using novel cationic solid lipid nanoparticles. Int J Pharm 2009, 365:206–213.PubMed
22.
Bowman MC, Ballard TE, Ackerson CJ, et al.: Inhibition of HIV fusion with multivalent gold nanoparticles. J Am Chem Soc 2008, 130:6896–6897.CrossRefPubMed
23.
Dou H, Grotepas CB, McMillan JM, et al.: Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of neuroAIDS. J Immunol 2009, 183:661–669.CrossRefPubMed
24.
Alexaki A, Liu Y, Wigdahl B: Cellular reservoirs of HIV-1 and their role in viral persistence. Curr HIV Res 2008, 6:388–400.CrossRefPubMed
25.
Han Y, Wind-Rotolo M, Yang HC, et al.: Experimental approaches to the study of HIV-1 latency. Nat Rev Microbiol 2007, 5:95–106.CrossRefPubMed
26.
Sahu GK, Paar D, Frost SD, et al.: Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells. J Med Virol 2009, 81:9–15.CrossRefPubMed
27.
Schnell G, Spudich S, Harrington P, et al.: Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia. PLoS Pathog 2009, 5:e1000395.CrossRefPubMed
28.
Richman DD, Margolis DM, Delaney M, et al.: The challenge of finding a cure for HIV infection. Science 2009, 323:1304–1307.CrossRefPubMed
29.
Archin NM, Keedy KS, Espeseth A, et al.: Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS 2009, 23:1799–1806.CrossRefPubMed
30.
Cysique LA, Brew BJ: Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 2009, 19:169–185.CrossRefPubMed
31.
Schweinsburg BC, Taylor MJ, Alhassoon OM, et al.: Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neurovirol 2005, 11:356–364.CrossRefPubMed
32.
• Liner J, Robertson K, Meeker R: Antiretroviral neurotoxicity. Poster presented at 39th Annual Neuroscience Meeting. Chicago, IL; 2009. This study demonstrates the potential neurotoxic mechanisms of ART on neuronal cultures.
33.
Ellis R, Langford D, Masliah E: HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 2007, 8:33–44.CrossRefPubMed
34.
Hammer SM, Eron JJ Jr, Reiss P, et al.: Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008, 300:555–570.CrossRefPubMed
35.
36.
Kitahata MM, Gange SJ, Abraham AG, et al: Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009, 360:1815–1826.CrossRefPubMed
37.
Ances BM, Sisti D, Vaida F, et al.: Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain. Neurology 2009, 73:702–708.CrossRefPubMed
38.
Marcondes MC, Flynn C, Huitron-Rezendiz S, et al.: Early antiretroviral treatment prevents the development of central nervous system abnormalities in simian immunodeficiency virus-infected rhesus monkeys. AIDS 2009, 23:1187–1195.CrossRefPubMed
39.
Villar Del Saz S, Sued O, Falco V, et al.: Acute meningoencephalitis due to human immunodeficiency virus type 1 infection in 13 patients: clinical description and follow-up. J Neurovirol 2008, 1–6.
40.
Harrington PR, Schnell G, Letendre SL, et al. Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. Aids 2009,23:907–915.CrossRefPubMed
41.
Gorman AA, Foley JM, Ettenhofer ML, et al.: Functional consequences of HIV-associated neuropsychological impairment. Neuropsychol Rev 2009, 19:186–203.CrossRefPubMed
42.
Owe-Larsson B, Sall L, Salamon E, Allgulander C: HIV infection and psychiatric illness. Afr J Psychiatry (Johannesbg) 2009, 12:115–128.
43.
Gutierrez-Valencia A, Viciana P, Palacios R, et al.: Stepped-dose versus full-dose efavirenz for HIV infection and neuropsychiatric adverse events: a randomized trial. Ann Intern Med 2009, 151:149–156.PubMed
44.
Morgan EE, Woods SP, Weber E, et al.: HIV-associated episodic memory impairment: evidence of a possible differential deficit in source memory for complex visual stimuli. J Neuropsychiatry Clin Neurosci 2009, 21:189–198.PubMed
45.
Woods SP, Iudicello JE, Moran LM, et al.: HIV-associated prospective memory impairment increases risk of dependence in everyday functioning. Neuropsychology 2008, 22:110–117.CrossRefPubMed
46.
Hubben GA, Bishai D, Pechlivanoglou P, et al.: The societal burden of HIV/AIDS in Northern Italy: an analysis of costs and quality of life. AIDS Care 2008, 20:449–455.CrossRefPubMed
47.
Zachariah R, Ford N, Philips M, et al.: Task shifting in HIV/AIDS: opportunities, challenges and proposed actions for sub-Saharan Africa. Trans R Soc Trop Med Hyg 2009, 103:549–558.CrossRefPubMed
48.
Robertson K, Liner J, Heaton R: Neuropsychological assessment of HIV-infected populations in international settings. Neuropsychol Rev 2009,19:232–249.CrossRefPubMed
49.
• Robertson K, Jiang H, Tripathy S, et al.: Improved neuropsychological function during HAART in diverse resource-limited settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study. In 16th Conference on Retroviruses and Opportunistic Infections. Montreal, CA; 2009. The ACTG 5199 study spanning seven developing countries reveals that ART is associated with NP improvement internationally, though the magnitude of improvement varies by country.
50.
Heaton RK, Cysique LA, Jin H, et al.: Neurobehavioral effects of human immunodeficiency virus infection among former plasma donors in rural China. J Neurovirol 2008, 1–14.
51.
Cysique LA, Jin H, Franklin DR Jr, et al.: Neurobehavioral effects of HIV-1 infection in China and the United States: a pilot study. J Int Neuropsychol Soc 2007, 13:781–790.PubMed
52.
Valcour VG, Shiramizu BT, Sithinamsuwan P, et al.: HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 Cohort Study. Neurology 2009, 72:992–998.CrossRefPubMed
53.
Sacktor N, Nakasujja N, Skolasky RL, et al.: Benefits and risks of stavudine therapy for HIV-associated neurologic complications in Uganda. Neurology 2009, 72:165–170.CrossRefPubMed
54.
55.
Sacktor N, Nakasujja N, Skolasky RL, et al.: HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda. Clin Infect Dis 2009, 49:780–786.CrossRefPubMed
56.
Gupta JD, Satishchandra P, Gopukumar K, et al.: Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India. J Neurovirol 2007, 13:195–202.CrossRefPubMed
Metadata
Title
HIV, Antiretroviral Therapies, and the Brain
Authors
Kevin J. Liner II
Michelle J. Ro
Kevin R. Robertson
Publication date
01-05-2010
Publisher
Current Science Inc.
Published in
Current HIV/AIDS Reports / Issue 2/2010
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI
https://doi.org/10.1007/s11904-010-0042-8

Other articles of this Issue 2/2010

Current HIV/AIDS Reports 2/2010 Go to the issue

ReviewPaper

Does Antiretroviral Therapy Increase or Decrease the Risk of Cardiovascular Disease?

ReviewPaper

Epidemiology of HIV Among Injecting and Non-injecting Drug Users: Current Trends and Implications for Interventions

ReviewPaper

Systems Biology-Based Approaches to Understand HIV-Exposed Uninfected Women

ReviewPaper

When to Start Antiretroviral Therapy

ReviewPaper

HIV and Aging: Time for a New Paradigm

ReviewPaper

Deconstructing Most Recent Antiretroviral Recommendations
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits