PMID- 16299731
OWN - NLM
STAT- MEDLINE
DCOM- 20060413
LR  - 20071115
IS  - 0146-6615 (Print)
IS  - 0146-6615 (Linking)
VI  - 78
IP  - 1
DP  - 2006 Jan
TI  - Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic 
      resistance to nucleoside and non-nucleoside inhibitors.
PG  - 9-17
AB  - An extended spectrum of HIV-1 reverse-transcriptase (RT) mutations in 
      HAART-treated patients has been recently described. To verify the possible 
      association of previously unreported RT mutations with a decrease of phenotypic 
      susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors, 
      the RT sequence of 328 HIV-1-positive patients (102 naive and 226 treated with 
      HAART participating in either the PhenGen or Genpherex study) was analyzed. All 
      treated patients were tested at the time of therapeutic failure with both 
      phenotypic (Antivirogram, Virco) and genotypic analyses (VircoGen); the frequency 
      of RT substitutions (positions 1-240) with respect to consensus B was compared to 
      that of naive patients using a Chi-square test. Amino acid changes at 13 
      positions not included in the IAS list of resistance-associated mutations were 
      detected more frequently in treated than in naive subjects. The mutations 
      involving 10 of these positions were associated with a reduced susceptibility to 
      antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were 
      correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR 
      were associated to NNRTI resistance. A correlation was found between K20R and 
      lamivudine resistance (P = 0.006) while T39A (P = 0.005), K43EQN (<0.001), E203KD 
      (P = 0.010), and H208Y (P = < 0.001) seemed to be associated with a previous use 
      of zidovudine and stavudine and with the development of thymidine analog 
      resistance. For H208Y, an association with use/resistance to abacavir (P = 0.004) 
      was also noted. D218E showed a weak association to didanosine resistance (P = 
      0.013). The data confirm that previously unreported mutations are associated with 
      antiretroviral drug experience and, more importantly, with a reduced 
      susceptibility to NRTIs and NNRTIs.
FAU - Saracino, A
AU  - Saracino A
AD  - Clinic of Infectious Diseases, University of Foggia, Foggia, Italy.
FAU - Monno, L
AU  - Monno L
FAU - Scudeller, L
AU  - Scudeller L
FAU - Cibelli, D C
AU  - Cibelli DC
FAU - Tartaglia, A
AU  - Tartaglia A
FAU - Punzi, G
AU  - Punzi G
FAU - Torti, C
AU  - Torti C
FAU - Lo Caputo, S
AU  - Lo Caputo S
FAU - Mazzotta, F
AU  - Mazzotta F
FAU - Scotto, G
AU  - Scotto G
FAU - Carosi, G
AU  - Carosi G
FAU - Angarano, G
AU  - Angarano G
LA  - eng
SI  - GENBANK/AY994317
SI  - GENBANK/AY994318
SI  - GENBANK/AY994319
SI  - GENBANK/AY994320
SI  - GENBANK/AY994321
SI  - GENBANK/AY994322
SI  - GENBANK/AY994323
SI  - GENBANK/AY994324
SI  - GENBANK/AY994325
SI  - GENBANK/AY994326
SI  - GENBANK/AY994327
SI  - GENBANK/AY994328
SI  - GENBANK/AY994329
SI  - GENBANK/AY994330
SI  - GENBANK/AY994331
SI  - GENBANK/AY994332
SI  - GENBANK/AY994333
SI  - GENBANK/AY994334
SI  - GENBANK/AY994335
SI  - GENBANK/AY994336
SI  - GENBANK/AY994337
SI  - GENBANK/AY994338
SI  - GENBANK/AY994339
SI  - GENBANK/AY994340
SI  - GENBANK/AY994341
SI  - GENBANK/AY994342
SI  - GENBANK/AY994343
SI  - GENBANK/AY994344
SI  - GENBANK/AY994345
SI  - GENBANK/AY994346
SI  - GENBANK/AY994347
SI  - GENBANK/AY994348
SI  - GENBANK/AY994349
SI  - GENBANK/AY994350
SI  - GENBANK/AY994351
SI  - GENBANK/AY994352
SI  - GENBANK/AY994353
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amino Acid Substitution
MH  - Anti-HIV Agents/*pharmacology
MH  - Drug Resistance, Viral/*genetics
MH  - Female
MH  - HIV Infections/drug therapy/*virology
MH  - HIV Reverse Transcriptase/*genetics
MH  - HIV-1/*drug effects/genetics/isolation & purification
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Reverse Transcriptase Inhibitors/*pharmacology
MH  - Sequence Analysis, DNA
MH  - Statistics as Topic
EDAT- 2005/11/22 09:00
MHDA- 2006/04/14 09:00
CRDT- 2005/11/22 09:00
PHST- 2005/11/22 09:00 [pubmed]
PHST- 2006/04/14 09:00 [medline]
PHST- 2005/11/22 09:00 [entrez]
AID - 10.1002/jmv.20500 [doi]
PST - ppublish
SO  - J Med Virol. 2006 Jan;78(1):9-17. doi: 10.1002/jmv.20500.