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Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease
journal contribution
posted on 2023-06-08, 16:41 authored by L Garvey, A Winston, J Walsh, F Post, K Porter, B Gazzard, M Fisher, C Leen, D Pillay, T Hill, M Johnson, R Gilson, J Anderson, P Easterbrook, L Bansi, C Orkin, J Ainsworth, A Palfreeman, M Gompels, A N Phillips, C A Sabin, The UK Collaborative HIV Cohort (CHIC) StudyOBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.
History
Publication status
- Published
Journal
NeurologyISSN
0028-3878Publisher
American Academy of NeurologyExternal DOI
Issue
8Volume
76Page range
693-700Department affiliated with
- Division of Medical Education Publications
Full text available
- No
Peer reviewed?
- Yes