Abstract
Combinations of antiretroviral drugs that prevent or delay the appearance of drug-resistant human immunodeficiency virus-type 1 (HIV-1) mutants are urgently required. Mutants resistant to 3'-azidothymidine (AZT, zidovudine) became phenotypically sensitive in vitro by mutation of residue 184 of viral reverse transcriptase to valine, which also induced resistance to (-)2'-deoxy-3'-thiacytidine (3TC). Furthermore, AZT-3TC coresistance was not observed during extensive in vitro selection with both drugs. In vivo AZT-3TC combination therapy resulted in a markedly greater decreased in serum HIV-1 RNA concentrations than treatment with AZT alone, even though valine-184 mutants rapidly emerged. Most samples assessed from the combination group remained AZT sensitive at 24 weeks of therapy, consistent with in vitro mutation studies.
Publication types
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Clinical Trial
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Clinical Trial, Phase II
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Clinical Trial, Phase III
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Randomized Controlled Trial
MeSH terms
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Antiviral Agents / pharmacology*
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Antiviral Agents / therapeutic use
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Base Sequence
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CD4 Lymphocyte Count
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Cell Line
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Codon
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Drug Resistance, Microbial
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Drug Therapy, Combination
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HIV Infections / drug therapy*
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HIV Infections / virology
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HIV Reverse Transcriptase
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HIV-1 / drug effects*
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HIV-1 / enzymology
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HIV-1 / genetics
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HIV-1 / growth & development
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HeLa Cells
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Humans
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Lamivudine
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Point Mutation
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RNA, Viral / blood
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RNA-Directed DNA Polymerase / genetics
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Reverse Transcriptase Inhibitors*
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Serial Passage
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Zalcitabine / analogs & derivatives*
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Zalcitabine / pharmacology
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Zalcitabine / therapeutic use
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Zidovudine / pharmacology*
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Zidovudine / therapeutic use
Substances
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Antiviral Agents
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Codon
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RNA, Viral
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Reverse Transcriptase Inhibitors
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Lamivudine
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Zidovudine
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Zalcitabine
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HIV Reverse Transcriptase
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RNA-Directed DNA Polymerase