Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease

Garvey, L, Winston, A, Walsh, J, Post, F, Porter, K, Gazzard, B, Fisher, M, Leen, C, Pillay, D, Hill, T, Johnson, M, Gilson, R, Anderson, J, Easterbrook, P, Bansi, L, Orkin, C, Ainsworth, J, Palfreeman, A, Gompels, M, Phillips, A N, Sabin, C A and The UK Collaborative HIV Cohort (CHIC) Study, (2011) Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease. Neurology, 76 (8). pp. 693-700. ISSN 0028-3878

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The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study.


Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations.


The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death.


Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Division of Medical Education
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Ellen Thomas
Date Deposited: 17 Feb 2014 09:41
Last Modified: 17 Feb 2014 09:41
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