title: Universal antiretroviral regimens: thinking beyond one-pill-once-a-day.
abstract: OBJECTIVE
  Poor adherence to oral antiretroviral treatment in a subpopulation of persons with HIV-1 infection interferes with the potential success of the drug regimens in treating the infection. Here, we review long-acting antiretroviral strategies currently in clinical development that could prove useful for the treatment of HIV-1 infection in individuals not succeeding with short-acting oral regimens.
  
  
  RESULTS
  Pharmaceutical nanotechnology has succeeded in creating two novel long-acting injectable antiretroviral compounds, carbotegravir and rilpivirine, which have completed early clinical trials demonstrating the safety, tolerability and prolonged antiretroviral activity. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA; MK8591) is a novel nucleoside reverse transcriptase inhibitor in early clinical development as a long-acting orally administered drug and in a long-acting polymer implant. Broadly neutralizing and cell-entry inhibitor monoclonal antibodies have demonstrated potent antiviral activity in early human trials; however, there is substantial baseline resistance. In addition, monotherapy leads to rapid resistance in those with baseline susceptibility.
  
  
  CONCLUSIONS
  Long-acting antiretroviral chemical compounds and monoclonal antibodies have demonstrated potent anti-HIV activity in the early-stage clinical investigations, and are actively being studied in advanced clinical trials for treatment and prevention. Strategies to manage toxicities and waning drug levels of chemical compounds, as well as primary and secondary resistance to current monoclonal antibodies are important considerations.
authors.affiliation: aDepartments of Medicine and Neuroscience, Center for Translational AIDS Research, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania bDivisions of Clinical Pharmacology and Infectious Diseases, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Charles W
authors.initials: CW
authors.lastname: Flexner
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000627:therapeutic use; D003839:Deoxyadenosines / Q000008:administration & dosage* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D007267:Injections; D053758:Nanoparticles; D018894:Reverse Transcriptase Inhibitors
chemical_list: D044966:Anti-Retroviral Agents; D003692:Delayed-Action Preparations; D003839:Deoxyadenosines; D018894:Reverse Transcriptase Inhibitors; C558823:islatravir