S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1

Antimicrob Agents Chemother. 1998 Jun;42(6):1340-5. doi: 10.1128/AAC.42.6.1340.


S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

MeSH terms

  • Animals
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology*
  • Cells, Cultured
  • Drug Resistance, Microbial
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Imidazoles / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes
  • Virus Replication / drug effects*


  • Anti-HIV Agents
  • Imidazoles
  • S 1153