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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Published on: December 11, 2017

Overcoming pharmacologic sanctuaries.

Theodore J Cory1, Timothy W Schacker, Mario Stevenson

  • 1Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy, Omaha, NE 68198, USA.

Current Opinion in HIV and AIDS
|March 5, 2013
PubMed
Summary
This summary is machine-generated.

Achieving a functional cure for HIV-1 is hindered by low antiretroviral drug levels in sanctuary sites. New strategies aim to increase drug concentrations in these reservoirs to improve HIV-1 treatment outcomes.

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Last Updated: May 13, 2026

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Area of Science:

  • Virology
  • Pharmacology
  • Immunology

Background:

  • Current antiretroviral therapy (ART) has improved HIV-1 management but has not achieved a cure.
  • Suboptimal antiretroviral drug concentrations in sanctuary sites (CNS, lymphoid tissue, macrophages) may impede a cure.
  • Understanding drug distribution is crucial for developing effective HIV-1 eradication strategies.

Purpose of the Study:

  • To review challenges in achieving adequate antiretroviral concentrations in HIV-1 sanctuary sites.
  • To explore strategies for overcoming barriers to effective drug distribution in these reservoirs.
  • To discuss the potential impact of optimized drug delivery on achieving an HIV-1 cure.

Main Methods:

  • Review of existing literature on antiretroviral drug distribution and pharmacokinetics in HIV-1 infection.
  • Analysis of data on drug concentrations in various body tissues and reservoirs.
  • Evaluation of novel strategies aimed at enhancing antiretroviral penetration into sanctuary sites.

Main Results:

  • Antiretroviral drug distribution is non-uniform, with low concentrations in certain tissues potentially promoting viral replication.
  • Several approaches, including drug modification and altered pharmacokinetics, are being investigated to boost drug levels in reservoirs.
  • Current methods show promise in increasing antiretroviral concentrations but have not yet led to complete HIV-1 clearance.

Conclusions:

  • Enhanced antiretroviral concentrations in viral sanctuaries may offer a path toward eliminating persistent HIV-1 reservoirs.
  • Further research is essential to optimize drug distribution for complete viral inhibition and prevention of resistance.
  • Targeting antiretroviral delivery to sanctuary sites is a critical area for advancing HIV-1 cure strategies.