Publication Abstract Display | Type: Published Manuscript | Title: Low CSF concentrations of the nucleotide HIV reverse transcriptase inhibitor, Tenofovir. | Authors: Best BM, Letendre SL, Koopmans P, Rossi SS, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Capparelli EV, Ellis RJ, Grant I, and the CHARTER Study Group | Year: 2012 | Publication: Journal of AIDS | Volume: 59 Issue: 4 Pages: 376-381 | Abstract:ABSTRACT: Tenofovir is a nucleotide HIV reverse transcriptase inhibitor whose chemical properties suggest that it may not penetrate into the central nervous system in therapeutic concentrations. The study objective was to determine tenofovir penetration into cerebrospinal fluid (CSF).CHARTER is a multi-center, observational study to determine effects of antiretroviral therapy on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within an hour of each other from subjects taking tenofovir between October 2003 and March 2007. All samples were assayed by mass spectrometry with a detection limit of 0.9 ng/mL.183 participants (age 44 ± 8 years; 83 ± 32 kg; 33 females; CSF protein 44 ± 16 mg/dL) had plasma and CSF samples drawn 12.2 ± 6.9 and 11 ± 7.8 hours post-dose respectively. Median plasma and CSF tenofovir concentrations were 96 ng/mL (IQR 47 - 153) and 5.5 ng/mL (IQR 2.7 - 11.3), respectively. Thirty-four of 231 (14.7%) plasma and 9/77 (11.7%) CSF samples were below detection. CSF/plasma concentration ratio from paired samples was 0.057 (IQR 0.03 - 0.1; n=38). Median CSF/wild-type IC50 ratio was 0.48 (IQR 0.24 - 0.98). Seventy-seven percent of CSF concentrations were below the tenofovir wild-type IC50. More subjects had detectable CSF HIV with lower (≤ 7 ng/mL) versus higher (> 7ng/mL) CSF tenofovir concentrations (29% vs. 9%; p=0.05).Tenofovir concentrations in the CSF are only 5% of plasma concentrations, suggesting limited transfer into the CSF, and possibly active transport out of the CSF. CSF tenofovir concentrations may not effectively inhibit viral replication in the CSF. |
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