Lamivudine or stavudine in two- and three-drug combinations against human immunodeficiency virus type 1 replication in vitro

J Infect Dis. 1996 Feb;173(2):355-64. doi: 10.1093/infdis/173.2.355.

Abstract

Two- and three-drug combinations of lamivudine or stavudine with other antiretroviral drugs were evaluated for activity against human immunodeficiency virus type 1 (HIV-1) activity in peripheral blood mononuclear cells. Other agents included zidovudine, didanosine, nevirapine, and saquinavir. Paired zidovudine-sensitive and -resistant clinical HIV-1 isolates were used. Additive or synergistic interactions were observed against the zidovudine-sensitive isolate with the following combinations: lamivudine-zidovudine, lamivudine-stavudine, lamivudine-saquinavir, lamivudine-nevirapine, stavudine-zidovudine, stavudine-didanosine, stavudine-saquinavir, stavudine-nevirapine, lamivudine-zidovudine-saquinavir, lamivudine-zidovudine-stavudine, stavudine-zidovudine-nevirapine, lamivudine-zidovudine-nevirapine, and stavudine-zidovudine-saquinavir. Against the zidovudine-resistant isolate, additive or synergistic interactions were seen with most two- and three-drug combinations, but the combination of stavudine-zidovudine was antagonistic. The clinical implications of these in vitro observations should be explored.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Drug Combinations
  • Drug Synergism
  • HIV Reverse Transcriptase
  • HIV Seropositivity / virology
  • HIV-1 / drug effects*
  • HIV-1 / isolation & purification
  • HIV-1 / physiology
  • Humans
  • Lamivudine
  • RNA-Directed DNA Polymerase / drug effects
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stavudine / pharmacology*
  • Virus Replication / drug effects*
  • Zalcitabine / analogs & derivatives*
  • Zalcitabine / pharmacology

Substances

  • Antiviral Agents
  • Drug Combinations
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Zalcitabine
  • Stavudine
  • HIV Reverse Transcriptase
  • RNA-Directed DNA Polymerase