PMID- 11920313
OWN - NLM
STAT- MEDLINE
DCOM- 20020507
LR  - 20071115
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 185
IP  - 7
DP  - 2002 Apr 1
TI  - Broad nucleoside-analogue resistance implications for human immunodeficiency 
      virus type 1 reverse-transcriptase mutations at codons 44 and 118.
PG  - 898-904
AB  - Two large, independent human immunodeficiency virus type 1 resistance databases 
      containing >7700 reverse-transcriptase (RT) sequences were used to analyze the 
      epidemiology of amino acid substitutions at codons 44 and 118, which confer 
      moderate lamivudine resistance in the presence of zidovudine resistance. As 
      expected, E44A/D and V118I mutations were strongly associated with M41L, D67N, 
      L210W, and T215Y but also with other mutations, including K43E/N/Q, T69D, V75M, 
      H208Y, R211K, and K219R. Both E44D and V118I were more frequently associated with 
      stavudine and didanosine than with zidovudine and lamivudine treatment. However, 
      selection of E44A/D and V118I was also detected in association with a switch to 
      other nucleoside RT inhibitors, including zalcitabine and abacavir. Site-directed 
      mutagenesis confirmed that 44D and 118I can decrease phenotypic susceptibility 
      not only to lamivudine but also to most other nucleoside analogues, particularly 
      stavudine and abacavir. Thus, substitutions at RT codons 44 and 118 have broad 
      implications in nucleoside RT inhibitor resistance in the setting of several 
      nucleoside-associated mutations.
FAU - Romano, Laura
AU  - Romano L
AD  - Sezione di Microbiologia, Dipartimento di Biologia Molecolare, Universita di 
      Siena, Siena, Italy. romanol@unisi.it
FAU - Venturi, Giulietta
AU  - Venturi G
FAU - Bloor, Stuart
AU  - Bloor S
FAU - Harrigan, Richard
AU  - Harrigan R
FAU - Larder, Brendan A
AU  - Larder BA
FAU - Major, Jennifer C
AU  - Major JC
FAU - Zazzi, Maurizio
AU  - Zazzi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020311
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Codon)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
SB  - IM
MH  - *Amino Acid Substitution
MH  - Anti-HIV Agents/pharmacology/therapeutic use
MH  - Codon/*genetics
MH  - *Drug Resistance, Multiple, Viral
MH  - HIV Infections/drug therapy/virology
MH  - HIV Reverse Transcriptase/*genetics
MH  - HIV-1/*drug effects/enzymology/genetics
MH  - Humans
MH  - Microbial Sensitivity Tests
MH  - Mutagenesis, Site-Directed
MH  - Mutation
MH  - Reverse Transcriptase Inhibitors/pharmacology/therapeutic use
EDAT- 2002/03/29 10:00
MHDA- 2002/05/08 10:01
CRDT- 2002/03/29 10:00
PHST- 2001/07/11 00:00 [received]
PHST- 2001/10/11 00:00 [revised]
PHST- 2002/03/29 10:00 [pubmed]
PHST- 2002/05/08 10:01 [medline]
PHST- 2002/03/29 10:00 [entrez]
AID - JID010811 [pii]
AID - 10.1086/339706 [doi]
PST - ppublish
SO  - J Infect Dis. 2002 Apr 1;185(7):898-904. doi: 10.1086/339706. Epub 2002 Mar 11.