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Göteborgs universitets publikationer

Antiviral activity and CSF concentrations of 600/100 mg of darunavir/ritonavir once daily in HIV-1 patients with plasma viral suppression

Författare och institution:
M. S. Di Yacovo (-); J. Molto (-); E. Ferrer (-); A. Curran (-); L. Else (-); Magnus Gisslén (Institutionen för biomedicin, avdelningen för infektionssjukdomar); B. Clotet (-); J. M. Tiraboschi (-); J. Niubo (-); A. Vila (-); Henrik Zetterberg (Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi); D. Back (-); D. Podzamczer (-)
Publicerad i:
Journal of Antimicrobial Chemotherapy, 70 ( 5 ) s. 1513-1516
ISSN:
0305-7453
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2015
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Objectives: The objective of this study was to assess whether a lower dose than the currently used one of darunavir/ritonavir might achieve good CSF concentrations and contribute to inhibition of CNS viral replication. Patients and methods: This was a substudy of a randomized, open, multicentre study (eudraCT 2011-006272-39), comparing the efficacy and safety of 800/100 mg of darunavir/ritonavir (darunavir 800) versus 600/100 mg of darunavir/ritonavir (darunavir 600) once daily plus tenofovir/emtricitabine or abacavir/lamivudine in 100 virologically suppressed patients. Paired blood and CSF samples were obtained. Total plasma darunavir concentrations were determined by HPLC, and CSF concentrations by liquid chromatography-tandem MS. Viral load (VL) was determined in plasma and CSF (limit of detection = 40 copies/mL) by PCR. Results: Sixteen patients were enrolled. The median (range) of darunavir CSF concentrations in darunavir 600 (n = 8) and darunavir 800 (n = 8) patients was 17.08 (5.79-30.19) and 13.23 (3.47-32.98) ng/mL, respectively (P = 0.916). The median (range) darunavir CSF: plasma ratio was 0.010 (0.005-0.022) in darunavir 600 patients and 0.008 (0.004-0.017) in the darunavir 800 arm (P = 0.370). All 16 patients had a VL <40 copies/mL in plasma and 14 had a VL <40 copies/mL in CSF. Of the two patients with detectable CSF VL (280 copies/mL and 159 copies/mL), one was receiving darunavir 600 and the other darunavir 800 plus tenofovir/emtricitabine. Of note, these patients had the lowest CSF darunavir concentrations in their respective groups: 5.79 ng/mL (802 ng/mL in plasma) and 3.47 ng/mL (958 ng/mL in plasma). Conclusions: Darunavir CSF and plasma concentrations were comparable between the two arms. However, one patient from each group (with the lowest CSF darunavir concentrations in their respective groups) had detectable CSF VL despite undetectable plasma VL.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Hematologi
Nyckelord:
antiretroviral therapy, HIV/AIDS, CSF, ART, CENTRAL-NERVOUS-SYSTEM, CEREBROSPINAL-FLUID, ANTIRETROVIRAL THERAPY, INFECTED PATIENTS, DARUNAVIR, PENETRATION, IMPACT, CNS, Infectious Diseases, Microbiology, Pharmacology & Pharmacy
Postens nummer:
219493
Posten skapad:
2015-07-06 15:27
Posten ändrad:
2016-05-18 08:05

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