Document Detail


Failure of atorvastatin to modulate CSF HIV-1 infection: results of a pilot study.
MedLine Citation:
PMID:  18695163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: HIV-1 infection of the CSF space is nearly universal in untreated systemic infection, and correlates strongly with intrathecal and systemic immunoactivation and CSF pleocytosis. Based on the potential immunomodulatory and antiviral properties of HMG-CoA reductase inhibitors (statins), we examined the effect of atorvastatin on CSF HIV-1 infection and associated CSF abnormalities in a small pilot study. METHODS: Seven male HIV-1-infected, antiretroviral-naïve subjects with a mean blood CD4+ T cell count of 473 cells/muL were studied in an open-label, single-arm pilot study to assess the effects of 80 mg atorvastatin daily for 8 weeks. The primary endpoint was the change in CSF HIV-1 RNA levels, both absolutely and relative to plasma HIV-1 RNA, at 4 and 8 weeks of treatment. Other outcome measures included CSF white blood cell counts and neopterin concentrations as indices of intrathecal immunoactivation, and blood HIV-1 RNA levels, neopterin concentrations, and T lymphocyte counts. Effects on blood lipids were used to monitor the established biologic effects of atorvastatin and treatment adherence. RESULTS: No significant changes in CSF virologic and inflammatory indices or in systemic HIV-1 infection were observed during atorvastatin treatment despite potent reduction of blood lipids. CONCLUSION: Atorvastatin showed no appreciable effect on CSF HIV-1 infection or intrathecal immunoactivation in this small uncontrolled study and thus appears to have little promise as an immunomodulatory adjuvant therapy for CNS HIV-1 infection, at least in neuroasymptomatic subjects with preserved CD4+ T cell counts.
Authors:
J C Probasco; S S Spudich; J Critchfield; E Lee; N Lollo; S G Deeks; R W Price
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurology     Volume:  71     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-12     Completed Date:  2008-10-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  521-4     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurology, University of California San Francisco, CA, USA. rwprice@sfgh.ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / therapeutic use*
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / drug effects
HIV Infections / cerebrospinal fluid*,  drug therapy*
HIV-1 / drug effects*
Heptanoic Acids / therapeutic use*
Humans
Male
Neopterin / blood
Pilot Projects
Pyrroles / therapeutic use*
Viral Load
Grant Support
ID/Acronym/Agency:
K23 MH074466/MH/NIMH NIH HHS; R01 MH62701/MH/NIMH NIH HHS; UL1 RR024131/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Heptanoic Acids; 0/Pyrroles; 110862-48-1/atorvastatin; 670-65-5/Neopterin
Comments/Corrections

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