Inhibition of HIV-1 replication in macrophages by red blood cell-mediated delivery of a heterodinucleotide of lamivudine and tenofovir

Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):953-7. doi: 10.1080/15257770701508067.

Abstract

Homo- and heterodimers of nucleoside/nucleotide analogues as reverse transcriptase inhibitors are effective on HIV-1-infected human monocyte-derived macrophages (M/M) compared to the single drugs or their combination. Since the combined treatment of lamivudine (3TC) and tenofovir ((R)PMPA) has an antiretroviral efficacy and a synergic effect respect to separate drugs, the heterodinucleotide 3TCpPMPA was synthesized. A single administration of the dimer as free drug or 3TCpPMPA-loaded RBC selectively targeted to M/M was able to almost completely protect macrophages from "de novo" infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis
  • Adenine / chemistry
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Drug Delivery Systems
  • Drug Design
  • Erythrocytes / metabolism
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Humans
  • In Vitro Techniques
  • Lamivudine / administration & dosage
  • Lamivudine / analogs & derivatives*
  • Lamivudine / chemical synthesis
  • Lamivudine / chemistry
  • Macrophages / drug effects
  • Macrophages / virology
  • Organophosphonates / administration & dosage*
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Tenofovir
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents
  • Organophosphonates
  • Lamivudine
  • Tenofovir
  • Adenine