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Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Pharmacology

Background:

  • Antiretroviral therapy (ART) simplification aims to reduce pill burden and potential toxicity.
  • Central nervous system (CNS) penetration and effects of ART are critical considerations during simplification.

Purpose of the Study:

  • To review current knowledge on CNS considerations in ART simplification strategies.
  • To evaluate the efficacy and tolerability of simplified ART regimens in the CNS.

Main Methods:

  • Literature review of studies on ART, CNS penetration, and simplification strategies.
  • Analysis of factors influencing virologic and neurocognitive outcomes in simplified ART regimens.

Main Results:

  • ART regimens effective in plasma are generally effective in cerebrospinal fluid (CSF).
  • ART simplification failure can occur with <2 active drugs, low genetic barrier drugs, or archived resistance.
  • Dual therapies with boosted protease inhibitors (PI) or dolutegravir (DTG) show CNS efficacy.
  • Switching from efavirenz (EFV) or DTG can resolve neurotoxicity, but non-ART factors may limit improvement.

Conclusions:

  • Careful selection of ART regimens is crucial for successful simplification while maintaining CNS efficacy.
  • Dual therapies with boosted PI or DTG offer effective CNS coverage.
  • Addressing non-ART related factors is important for complete resolution of CNS symptoms in patients on simplified ART.