Publikation
Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid
Wissenschaftlicher Artikel/Review - 01.01.2013
Cusini Alexia, Günthard Huldyrich F, Opravil Milos, Gutmann Christine, Zenger Franziska, Klimkait Thomas, Cavassini Matthias, Gaudenz Roman, Hirschel Bernhard, Widmer Nicolas, Rohrbach Janine, Fux Christoph A, Ledergerber Bruno, Decosterd Laurent A, Yerly Sabine, Vernazza Pietro, Swiss HIV Cohort Study
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OBJECTIVES
To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments with higher central nervous system penetration-effectiveness (CPE) achieve better CSF viral suppression.
METHODS
Viral loads (VLs) and drug concentrations of lopinavir, atazanavir, and efavirenz were measured in plasma and CSF. The CPE was calculated using 2 different methods.
RESULTS
The authors analyzed 87 CSF samples of 60 patients. In 4 CSF samples, HIV-1 RNA was detectable with 43-82 copies per milliliter. Median CPE in patients with detectable CSF VL was significantly lower compared with individuals with undetectable VL: CPE of 1.0 (range, 1.0-1.5) versus 2.3 (range, 1.0-3.5) using the method of 2008 (P = 0.011) and CPE of 6 (range, 6-8) versus 8 (range, 5-12) using the method of 2010 (P = 0.022). The extrapolated CSF trough levels for atazanavir (n = 12) were clearly above the 50% inhibitory concentration (IC50) in only 25% of samples; both patients on atazanavir/ritonavir with detectable CSF HIV-1 RNA had trough levels in the range of the presumed IC50. The extrapolated CSF trough level for lopinavir (n = 42) and efavirenz (n = 18) were above the IC50 in 98% and 78%, respectively, of samples, including the patients with detectable CSF HIV-1 RNA.
CONCLUSIONS
This study suggests that treatment regimens with high intracerebral efficacy reflected by a high CPE score are essential to achieve CSF HIV-1 RNA suppression. The CPE score including all drug components was a better predictor for treatment failure in the CSF than the sole concentrations of protease inhibitor or nonnucleoside reverse transcriptase inhibitor in plasma or CSF.