ABSTRACT
Summary................................................................................................................ 178 Introduction............................................................................................................ 178 Inhibition.of.HIV-1.Replication.(Cytopathicity).................................................... 179 Emergence.of.Drug-resistant.HIV-1.Mutants......................................................... 186 Cross-Resistance.of.Thiocarboxanilide.Derivatives.with.Other.NnrtIs................ 188 Switching.from.One.Compound.to.Another.......................................................... 188 Drug.Combinations................................................................................................ 191 HIV-1.Knockout.Concentrations............................................................................ 192 HIV-1.Knockout.Concentrations.of.Different.Drugs.Combined........................... 193 Conclusion.............................................................................................................. 194 Acknowledgments.................................................................................................. 196 References............................................................................................................... 196
The.thiocarboxanilides.fulfill.the.requirements.of.ideal.anti-HIV-1.drug.candidates.. They.are.highly.potent.and.selective.inhibitors.of.HIV-1.replication.that.are.targeted. at.the.nonsubstrate.binding.site.of.the.HIV-1.reverse.transcriptase..Like.all.the.other. nonnucleoside.reverse.transcriptase.inhibitors.(NNRTIs),.they.lead.to.the.emergence. of. drug-resistant. virus. strains.. Yet,. resistance. development. in. cell. culture. can. be. circumvented.by.(1).switching.from.one.NNRTI.(i.e.,.thiocarboxanilide).to.another;. (2).combining.thiocarboxanilides.with.other.NNRTIs;.(3).using.the.thiocarboxanilides.from.the.start.at.sufficiently.high.(“knockout”).concentrations;.and.(4).starting. with.combinations.of.thiocarboxanilides.and.other.drugs.(whether.NNRTIs.or.not). at.knockout.concentrations.so.as.to.completely.suppress.virus.replication.and.thus. prevent.resistance.from.emerging.
