title: Long-acting slow effective release antiretroviral therapy.
abstract: 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.
authors.affiliation: a Department of Pharmacology and Experimental Neuroscience , University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Benson
authors.initials: B
authors.lastname: Edagwa
authors.affiliation: a Department of Pharmacology and Experimental Neuroscience , University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: JoEllyn
authors.initials: J
authors.lastname: McMillan
authors.affiliation: a Department of Pharmacology and Experimental Neuroscience , University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Brady
authors.initials: B
authors.lastname: Sillman
authors.affiliation: a Department of Pharmacology and Experimental Neuroscience , University of Nebraska Medical Center , Omaha , NE , USA.|b Departments of Pharmaceutical Sciences , University of Nebraska Medical Center , Omaha , NE , USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004279:DNA, Viral; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000893:Anti-Inflammatory Agents; D004279:DNA, Viral; D003692:Delayed-Action Preparations; D018696:Neuroprotective Agents; D011355:Prodrugs
keywords: Antiretroviral therapy; HIV-1 proviral excision; anti-inflammatory activities; long-acting slow effective release; nanoformulated ART; neuroprotection; prodrugs; targeted drug delivery; theranostics; viral reservoirs