Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid.

Détails

ID Serval
serval:BIB_84E92CDBD71B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid.
Périodique
Journal of Acquired Immune Deficiency Syndromes
Auteur(s)
Cusini A., Vernazza P.L., Yerly S., Decosterd L.A., Ledergerber B., Fux C.A., Rohrbach J., Widmer N., Hirschel B., Gaudenz R., Cavassini M., Klimkait T., Zenger F., Gutmann C., Opravil M., Günthard H.F.
Collaborateur(s)
Swiss HIV Cohort Study
Contributeur(s)
Barth J., Battegay M., Bernasconi E., Böni J., Bucher HC., Burton-Jeangros C., Calmy A., Cavassini M., Cellerai C., Egger M., Elzi L., Fehr J., Fellay J., Flepp M., Francioli P., Furrer H., Fux CA., Gorgievski M., Günthard H., Haerry D., Hasse B., Hirsch HH., Hirschel B., Hösli I., Kahlert C., Kaiser L., Keiser O., Kind C., Klimkait T., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Metzner K., Müller N., Nadal D., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schöni-Affolter F., Schüpbach J., Speck R., Taffé P., Tarr P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1944-7884 (Electronic)
ISSN-L
1525-4135
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
62
Numéro
1
Pages
28-35
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
OBJECTIVES: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments with higher central nervous system penetration-effectiveness (CPE) achieve better CSF viral suppression.
METHODS: Viral loads (VLs) and drug concentrations of lopinavir, atazanavir, and efavirenz were measured in plasma and CSF. The CPE was calculated using 2 different methods.
RESULTS: The authors analyzed 87 CSF samples of 60 patients. In 4 CSF samples, HIV-1 RNA was detectable with 43-82 copies per milliliter. Median CPE in patients with detectable CSF VL was significantly lower compared with individuals with undetectable VL: CPE of 1.0 (range, 1.0-1.5) versus 2.3 (range, 1.0-3.5) using the method of 2008 (P = 0.011) and CPE of 6 (range, 6-8) versus 8 (range, 5-12) using the method of 2010 (P = 0.022). The extrapolated CSF trough levels for atazanavir (n = 12) were clearly above the 50% inhibitory concentration (IC50) in only 25% of samples; both patients on atazanavir/ritonavir with detectable CSF HIV-1 RNA had trough levels in the range of the presumed IC50. The extrapolated CSF trough level for lopinavir (n = 42) and efavirenz (n = 18) were above the IC50 in 98% and 78%, respectively, of samples, including the patients with detectable CSF HIV-1 RNA.
CONCLUSIONS: This study suggests that treatment regimens with high intracerebral efficacy reflected by a high CPE score are essential to achieve CSF HIV-1 RNA suppression. The CPE score including all drug components was a better predictor for treatment failure in the CSF than the sole concentrations of protease inhibitor or nonnucleoside reverse transcriptase inhibitor in plasma or CSF.
Mots-clé
Adult, Anti-Retroviral Agents/administration & dosage, Anti-Retroviral Agents/pharmacokinetics, Antiretroviral Therapy, Highly Active/methods, Benzoxazines/administration & dosage, Benzoxazines/pharmacokinetics, Cerebrospinal Fluid/chemistry, Cerebrospinal Fluid/virology, Female, HIV Infections/drug therapy, HIV Infections/virology, HIV-1/isolation & purification, Humans, Lopinavir/administration & dosage, Lopinavir/pharmacokinetics, Male, Middle Aged, Oligopeptides/administration & dosage, Oligopeptides/pharmacokinetics, Plasma/chemistry, Plasma/virology, Pyridines/administration & dosage, Pyridines/pharmacokinetics, RNA, Viral/cerebrospinal fluid, Treatment Outcome, Viral Load
Pubmed
Web of science
Création de la notice
17/01/2013 19:12
Dernière modification de la notice
03/03/2018 18:55
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