Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains

Molecules. 2018 Jul 2;23(7):1599. doi: 10.3390/molecules23071599.

Abstract

Reverse transcriptase inhibitors (RTIs), including nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs), are critical antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infection. Emergence of multi-RTI resistance calls for the development of more potent therapeutics or regimens against RTI-resistant strains. Here, we demonstrated that combining azidothymidine (AZT) with a new NNRTIs under development, diarylpyridine (DAPA)-2e, diarylanilin (DAAN)-14h, or DAAN-15h, resulted in strong synergism against infection by divergent HIV-1 strains, including those resistant to NRTIs and NNRTIs, suggesting the potential for developing these novel NNRTIs as salvage therapy for HIV/acquired immune deficiency syndrome (AIDS) patients.

Keywords: HAART; HIV-1; NNRTIs; antiviral activity; combination; synergism.

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / metabolism
  • Anti-HIV Agents / pharmacology*
  • Drug Interactions
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects*
  • Humans
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Zidovudine / pharmacology*

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • HIV Reverse Transcriptase