Document Detail


Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid.
MedLine Citation:
PMID:  23018371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Alexia Cusini; Pietro L Vernazza; Sabine Yerly; Laurent A Decosterd; Bruno Ledergerber; Christoph A Fux; Janine Rohrbach; Nicolas Widmer; Bernhard Hirschel; Roman Gaudenz; Matthias Cavassini; Thomas Klimkait; Franziska Zenger; Chistine Gutmann; Milos Opravil; Huldyrich F Günthard;
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  62     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-24     Completed Date:  2013-02-26     Revised Date:  2014-02-06    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  28-35     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-Retroviral Agents / administration & dosage*,  pharmacokinetics*
Antiretroviral Therapy, Highly Active / methods*
Benzoxazines / administration & dosage,  pharmacokinetics
Cerebrospinal Fluid / chemistry,  virology*
Female
HIV Infections / drug therapy*,  virology
HIV-1 / isolation & purification*
Humans
Lopinavir / administration & dosage,  pharmacokinetics
Male
Middle Aged
Oligopeptides / administration & dosage,  pharmacokinetics
Plasma / chemistry,  virology
Pyridines / administration & dosage,  pharmacokinetics
RNA, Viral / cerebrospinal fluid
Treatment Outcome
Viral Load*
Chemical
Reg. No./Substance:
0/Anti-Retroviral Agents; 0/Benzoxazines; 0/Oligopeptides; 0/Pyridines; 0/RNA, Viral; 2494G1JF75/Lopinavir; JE6H2O27P8/efavirenz; QZU4H47A3S/atazanavir
Investigator
Investigator/Affiliation:
J Barth / ; M Battegay / ; E Bernasconi / ; J Böni / ; H C Bucher / ; C Burton-Jeangros / ; A Calmy / ; M Cavassini / ; C Cellerai / ; M Egger / ; L Elzi / ; J Fehr / ; J Fellay / ; M Flepp / ; P Francioli / ; H Furrer / ; C A Fux / ; M Gorgievski / ; H Günthard / ; D Haerry / ; B Hasse / ; H H Hirsch / ; B Hirschel / ; I Hösli / ; C Kahlert / ; L Kaiser / ; O Keiser / ; C Kind / ; T Klimkait / ; H Kovari / ; B Ledergerber / ; G Martinetti / ; B Martinez de Tejada / ; K Metzner / ; N Müller / ; D Nadal / ; G Pantaleo / ; A Rauch / ; S Regenass / ; M Rickenbach / ; C Rudin / ; P Schmid / ; D Schultze / ; F Schöni-Affolter / ; J Schüpbach / ; R Speck / ; P Taffé / ; P Tarr / ; A Telenti / ; A Trkola / ; P Vernazza / ; R Weber / ; S Yerly /
Comments/Corrections
Comment In:
J Acquir Immune Defic Syndr. 2013 Apr 1;62(4):e118-9   [PMID:  24135736 ]
Erratum In:
J Acquir Immune Defic Syndr. 2013 Aug 15;63(5):e170-1

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