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Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Caniglia Ellen C, Cain Lauren E, Justice Amy, Tate Janet, Logan Roger, Sabin Caroline, Winston Alan, van Sighem Ard, Miro Jose M, Podzamczer Daniel, Olson Ashley, Arribas José Ramón, Moreno Santiago, Meyer Laurence, del Romero Jorge, Dabis François, Bucher Heiner C, Wandeler Gilles, Vourli Georgia, Skoutelis Athanasios, Lanoy Emilie, Gasnault Jacques, Costagliola Dominique, Hernán Miguel A,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal Neurology
Volume (Issue) 83(2)
Page(s) 134 - 41
Title of proceedings Neurology
DOI 10.1212/wnl.0000000000000564

Open Access

URL https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24907236/
Type of Open Access Repository (Green Open Access)

Abstract

The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.
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