| Higher CNS Penetration-Effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid. | |
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MedLine Citation:
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PMID: 23018371 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE:: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments (cART) with higher CNS penetration effectiveness (CPE) achieve better CSF viral suppression. METHODS:: Viral loads and drug concentrations of lopinavir, atazanavir and efavirenz, were measured in plasma and CSF. The CPE was calculated using two different methods. RESULTS:: We analysed 87 CSF samples of 60 patients. In 4 CSF samples HIV-1 RNA was detectable with 43 to 82 copies/mL. Median CPE in patients with detectable CSF viral load was significantly lower compared to individuals with undetectable viral load: 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) with the method of 2010 (p= 0.022). The extrapolated CSF trough levels for atazanavir (n=12) were clearly above the IC50 in only 25% of samples; both patients on atazanavir/r 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% respectively 78% 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 PI or NNRTI in plasma or CSF. |
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Authors:
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A Cusini; P L Vernazza; S Yerly; L A Decosterd; B Ledergerber; C A Fux; J Rohrbach; N Widmer; B Hirschel; R Gaudenz; M Cavassini; Th Klimkait; F Zenger; C Gutmann; M Opravil; H F Günthard; |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-26 |
Journal Detail:
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Title: Journal of acquired immune deficiency syndromes (1999) Volume: - ISSN: 1944-7884 ISO Abbreviation: J. Acquir. Immune Defic. Syndr. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100892005 Medline TA: J Acquir Immune Defic Syndr Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich 2Division of Infectious Diseases Cantonal Hospital St. Gallen 3Laboratory of Virology Geneva University Hospital 4Division of Clinical Pharmacology, University Hospital Centre and University of Lausanne 5Division of Infectious Diseases University Hospital Bern 6Division of Infectious Diseases University Hospital Geneva 7Division of Infectious Diseases University Hospital Lausanne 8Department of Biomedicine, University of Basel 9Division of Infectious Diseases Cantonal Hospital Aarau, Switzerland. |
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