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Science. 1995 Aug 4;269(5224):696-9.

Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy.

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  • 1Antiviral Therapeutic Research Unit, Wellcome Research Laboratories, Beckenham, Kent, UK.

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.

PMID:
7542804
[PubMed - indexed for MEDLINE]
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