Maraviroc concentrations in cerebrospinal fluid in HIV-infected patients.
OBJECTIVE
To determine maraviroc (MVC) concentrations in cerebrospinal fluid (CSF) in HIV-infected patients.


METHODS
Twelve CCR5+ HIV-1 adult antiretroviral-experienced patients receiving MVC-containing regimens for at least 1 month were enrolled. Both CSF and blood samples were taken around 12 hours after the last MVC dose. liquid chromatography tandem mass spectrometry was used to determine MVC concentrations, and HIV-1 viral load was determined by real-time polymerase chain reaction, (LOD, 40 copies/mL).


RESULTS
Twelve blood and 12 CSF samples were collected. Median CD4 count was 281(120-759) cells per microliter, and median HIV-1 viral load was <40 copies per milliliter. Median time on MVC was 13.5 weeks (4-60). Nucleoside analogues (tenofovir/didanosine) were given in only 1 case. Median MVC concentrations in plasma were 124.75 (7.3-517) ng/mL. In all except one, CSF sample-receiving an erroneous MVC dose while taking concomitantly nevirapine-MVC concentrations [2.58 (<0.5-7.22) ng/mL] were within the EC(90) range (0.06-10.70). Median MVC CSF: plasma ratio was 0.022 (0.004-0.17), and when the free MVC plasma concentration was used, 0.094 (2.58-27.44). CSF viral load was <40 copies per milliliter in all 9 patients with undetectable plasma viral load.


CONCLUSIONS
MVC achieves concentrations within the EC(90) range in CSF. All patients with undetectable plasma viral load although receiving nucleoside-sparing regimens including new drugs showed viral suppression in CSF.
Tiraboschi
Juan Manuel
JM
HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Niubo
Jordi
J
Curto
Jordi
J
Podzamczer
Daniel
D
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D002853:Chromatography, Liquid; D003510:Cyclohexanes / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D000068698:Tenofovir; D014230:Triazoles / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D063065:Organophosphonates; D014230:Triazoles; D000068698:Tenofovir; D000225:Adenine; D016049:Didanosine; D000077592:Maraviroc