Long-acting slow effective release antiretroviral therapy

ABSTRACT

Introduction: Advances in long-acting antiretroviral therapy (ART) can revolutionize current HIV/AIDS treatments. We coined the term ‘long-acting slow effective release ART’ (LASER ART) to highlight the required formulation properties of slow drug dissolution, poor water-solubility, bioavailability, little-to-no off-target toxicities and improved regimen adherence. Drug carrier technologies characterized by high antiretroviral drug (ARV) payloads in a single carrier improve the pharmacokinetic and pharmacodynamic profiles. The surface modifications of ARV carriers target monocyte-macrophages and facilitate drug transport across physiological barriers and to virus-susceptible CD4 + T cells.

Areas covered: The review highlights developments of reservoir-targeted LASER ART for improved therapeutic outcomes. Such nanoART delivery platforms include decorated multifunctional nano- and micro-particles, prodrugs and polymer conjugates. Therapeutic strategies such as gene-editing technologies boost ART effectiveness.

Expert opinion: The persistence of HIV-1 in lymphoid, gut and nervous system reservoirs poses a challenge to viral eradication. Emerging slow-release drug carriers can target intracellular pathogens, activate antiviral immunity, promote genome editing, sustain drug depots and combine therapeutics with image contrast agents, and can meet unmet clinical needs for HIV-infected patients. Such efforts will bring the medicines to reservoir sites and accelerate viral clearance.

KEYWORDS:

• Antiretroviral therapy
• viral reservoirs
• long-acting slow effective release
• nanoformulated ART
• targeted drug delivery
• HIV-1 proviral excision
• anti-inflammatory activities
• neuroprotection
• theranostics
• prodrugs

Article highlights

• Long-acting slow effective release of antiretroviral therapy for patient regimen adherence

• Macrophage carriage of antiretroviral therapy for drug delivery

• Particle decoration with targeting ligands that promote cell and tissue entry

• Polymer encased hydrophobic prodrugs and conjugates

• Magnetite nanoparticles as theranostic tools for assessment of ART biodistribution

• Autophagy stimulation facilitates intracellular accumulation of ARV nanoparticles

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by National Institutes of Health grants P01 DA028555, R01 NS36126, P01 NS31492, 2R01 NS034239, P01 MH64570, P01 NS43985, P30 MH062261 and R01 AG043540.