Document Detail

Overcoming pharmacologic sanctuaries.
MedLine Citation:
PMID:  23454865     Owner:  NLM     Status:  MEDLINE    
PURPOSE OF REVIEW: Current antiretroviral treatment regimens represent significant improvements in the management of HIV-1 infection; however, these regimens have not achieved a functional or sterilizing cure. One barrier to achieving a cure may be suboptimal antiretroviral concentrations in sanctuary sites throughout the body, including the central nervous system, gut-associated lymphoid tissue, lymph nodes, and tissue macrophages. This review will focus on the problems associated with achieving effective concentrations in these restricted sanctuary sites, and potential strategies to overcome these barriers.
RECENT FINDINGS: Sufficient data exist to conclude that antiretroviral drug distribution is not uniform throughout the body. Low tissue/reservoir concentrations may be associated with viral replication. Multiple means to increase drug concentrations in sanctuary sites are being investigated, including modification of currently utilized drugs, blockade of transporters and enzymes that affect drug metabolism and pharmacokinetics, and local drug administration. Accumulating data suggest these methods increase antiretroviral concentrations in reservoirs of viral replication. No method has yet resulted in the complete clearance of HIV.
SUMMARY: New strategies for increasing antiretroviral concentrations in predominant sites of viral replication may provide more effective means for elimination of viral sanctuaries. Additional research is necessary to optimize antiretroviral tissue distribution in order to inhibit virus replication fully, and avoid resistance and replenishment of viral reservoirs that may persist in the face of antiretroviral therapy.
Theodore J Cory; Timothy W Schacker; Mario Stevenson; Courtney V Fletcher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current opinion in HIV and AIDS     Volume:  8     ISSN:  1746-6318     ISO Abbreviation:  Curr Opin HIV AIDS     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-09-25     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  101264945     Medline TA:  Curr Opin HIV AIDS     Country:  United States    
Other Details:
Languages:  eng     Pagination:  190-5     Citation Subset:  IM; X    
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MeSH Terms
Anti-HIV Agents / administration & dosage*,  pharmacokinetics*
Drug Resistance, Viral
HIV Infections / drug therapy*,  metabolism*,  virology
Tissue Distribution
Grant Support
Reg. No./Substance:
0/Anti-HIV Agents

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