| Publication Abstract Display | | Type: Published Abstract | | Title: Raltegravir concentrations in CSF exceed the median inhibitory concentration. | | Authors: Letendre S, Rossi S, Best B, Way L, Ueland S, Grant I, Ellis R, Capparelli E, and the HNRC Group | | Year: 2009 | | Publication: 49th Interscience Conference on Antimicrobial Agents & Chemotherapy | | Volume: A1-1311 Issue: Pages: 44 | | Abstract:Background: HIV-associated neurocognitive disorders continue to be highly prevalent in domestic and international settings. Antiretrovirals (ARVs) that achieve higher concentrations in CSF are associated with better control of HIV and improved neuropsychological performance. The objective of this study was to measure raltegravir (RTG) in CSF and compare the findings to concentrations in matched blood specimens and in vitro inhibitory concentrations.
Methods: 18 HIV-infected participants (pts) were evaluated at the UCSD HIV Neurobehavioral Research Center between April 2007 and February 2009 and were selected based on use of RTG-containing regimens and the availability of CSF and blood plasma stored at -70oC since collection. Raltegravir was measured in 22 CSF and matched plasma specimens by HPLC (plasma) or LC/MS (CSF). The lower limit of detection of each assay was 5 ng/mL. HIV RNA was measured by RT-PCR (limit of quantitation 50 copies/mL). Concentrations were compared to the median inhibitory concentration (IC50) for wild-type HIV (3.4 ng/mL). Descriptive and bivariate statistics were calculated using standard methods.
Results: Pts were mostly middle-aged (median 46 years) white (89%) men (94%) with AIDS (83%) who did not have HCV co-infection (88%). Median CD4 count at assessment was 276 and 28% were below 200/µL. HIV RNA was detectable in 38% of blood and 4% of CSF specimens. Median duration of RTG was 4.2 months. RTG was present in all CSF specimens with a median concentration of 13.9 ng/mL (IQR 8.9, 24.6). The median CSF-to-plasma ratio was 7.3% (IQR 2.2%, 17%). CSF concentrations correlated with plasma concentrations (rho = 0.47, p = 0.03) but not with post-dose sampling time. RTG concentrations in CSF exceeded the IC50 of wild-type HIV in all but 1 specimen by a median of 4.1-fold (IQR 2.6, 7.2).
Conclusions: Raltegravir is present in CSF and reaches sufficiently high concentrations to inhibit wild-type HIV in nearly all individuals. Regimens containing raltegravir should contribute to control of HIV replication in the nervous system as a component of effective antiretroviral regimens. |
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