Ultra-long-acting removable drug delivery system for HIV treatment and prevention

Nat Commun. 2018 Oct 8;9(1):4156. doi: 10.1038/s41467-018-06490-w.


Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. We use two pre-clinical models for HIV transmission and treatment, non-human primates (NHP) and humanized BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously administered ultra-LA dolutegravir effectively delivers the drug in both models and show suppression of viremia and protection from multiple high-dose vaginal HIV challenges in BLT mice. This approach represents a potentially effective strategy for the ultra-LA drug delivery with multiple possible therapeutic applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use*
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • HIV Infections / drug therapy*
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Macaca mulatta
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Oxazines
  • Piperazines
  • Pyridones
  • Time Factors
  • Tissue Distribution
  • Virus Replication / drug effects
  • Virus Replication / genetics


  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir