Raltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection |
| |
Authors: | Aylin Yilmaz Magnus Gisslén Serena Spudich Evelyn Lee Anura Jayewardene Francesca Aweeka Richard W Price |
| |
Institution: | 1. Department of Infectious Diseases, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; 2. Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.; 3. Department of Pharmacology, University of California San Francisco, San Francisco, California, United States of America.;Instituto de Pesquisa Clinica Evandro Chagas, FIOCRUZ, Brazil |
| |
Abstract: | IntroductionRaltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug.MethodsRaltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma.ResultsTwenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0–126.0). The median plasma raltegravir concentration was 448 ng/ml (range, 37–5180). CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations.ConclusionsApproximately 50% of the CSF specimens exceeded the IC95 levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry. |
| |
Keywords: | |
|
|