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Publication Abstract Display
Type: Published Manuscript
Title: Total Raltegravir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for wild-type HIV-1.
Authors: Croteau D, Letendre S, Best BM, Ellis RJ, Breidinger S, Clifford D, Collier A, Gelman B, Marra C, Mbeo G, McCutchan A, Morgello S, Simpson D, Way L, Vaida F, Ueland S, Capparelli E, Grant I; and the CHARTER Group
Year: 2010
Publication: Antimicrobial Agents and Chemotherapy
Volume: 54 Issue: Pages: 5156-5160
Abstract:HIV-associated neurocognitive disorders continue to be common. Antiretrovirals that achieve higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV and improved cognition. The objective of this study was to measure total raltegravir (RAL) concentrations in CSF and to compare them with matched plasma concentrations and in vitro inhibitory concentrations. Eighteen subjects with HIV-1 infection were enrolled based on use of RAL-containing regimens and availability of CSF and matched plasma. RAL was measured in 21 CSF and plasma pairs by liquid chromatography tandem mass spectrometry and HIV RNA by RT-PCR. RAL concentrations were compared to the 50% inhibitory concentration (IC50) for wild-type HIV-1 (3.2 ng/mL). Volunteers were predominantly middle-aged white men with AIDS and without HCV co-infection. Median concurrent CD4+ cell count was 276/μL and 28% were below 200/μL. HIV RNA was detectable in 38% of plasma and 4% of CSF specimens. RAL was present in all CSF specimens with a median total concentration of 14.5 ng/mL. The median plasma concentration was 260.9 ng/mL with a median CSF-toplasma ratio of 0.058. CSF concentrations correlated with plasma concentrations (r2 = 0.24, p = 0.02) but not with post-dose sampling time (p > 0.50). RAL concentrations in CSF exceeded the IC50 of wild-type HIV in all specimens by a median of 4.5-fold. RAL is present in CSF and reaches sufficiently high concentrations to inhibit wild-type HIV in all individuals. RAL likely contribute to the control of HIV replication in the nervous system as a component of effective antiretroviral regimens or as the main antiretroviral.

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