Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy.
Science
; 269(5224): 696-9, 1995 Aug 04.
Article
in En
| MEDLINE
| ID: mdl-7542804
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Zidovudine
/
HIV Infections
/
HIV-1
/
Zalcitabine
/
Reverse Transcriptase Inhibitors
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
Science
Year:
1995
Type:
Article
Affiliation country:
United kingdom