PMID- 10792990
OWN - NLM
STAT- MEDLINE
DCOM- 20000613
LR  - 20071115
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 270
IP  - 2
DP  - 2000 May 10
TI  - Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain 
      and MDR mutations) of HIV-1 reverse transcriptase from extensively treated 
      patients: incidence and association with other resistance mutations.
PG  - 310-6
AB  - Multiple nucleoside resistance involves specific mutational patterns of the HIV-1 
      pol gene that are independent of the classic mutations conferring resistance to 
      individual dideoxynucleosides. These include a cluster of five mutations in the 
      reverse-transcriptase (RT) coding region (A62V, V75I, F77L, F116Y, and Q151M) 
      generally referred to as multidrug resistance (MDR) mutations, and insertions of 
      one or several amino acid residues between codons 67 and 70 of RT, a flexible 
      region joining two antiparrallel beta sheets (beta3-beta4 insertions). The 
      objectives of this study were (i) to determine the prevalence of multidrug 
      resistance genotypes (MDR mutations and beta3-beta4 insertions) in a cohort of 
      632 patients who were extensively pretreated with anti-HIV drugs and not 
      responding to their current antiretroviral therapy, and (ii) to analyze the 
      association of multidrug resistance genotypes with other resistance mutations in 
      the RT and protease genes. Among viruses sequenced from these patients, 15 (2.4%) 
      of them contained an insertion and 2 (0.3%) contained a deletion in the 
      beta3-beta4 finger subdomain of RT. In 9 cases, the insertion was associated with 
      a D67S, G, or E mutation. In addition, we identified 13 (2.1%) viruses harboring 
      specific MDR mutations (mainly Q151M and/or A62V, V75I, F116Y). Interestingly, 
      the A62V mutation was found in 6 of the 15 strains with an insertion, whereas the 
      other MDR mutations were not observed in insertion mutant strains. Especially 
      high levels of resistance to zidovudine were observed for viruses with a 
      beta3-beta4 insertion in the background of A62V, L210W, and T215Y. Otherwise, MDR 
      mutations and beta3-beta4 insertions were found in association with the classic 
      mutations conferring resistance to zidovudine, lamivudine, nonnucleoside RT 
      inhibitors, and protease inhibitors, according to treatment history. Finally, we 
      observed a genome with a deletion of codon 70 associated with a Q151M MDR 
      mutation. These data suggest that the emergence of HIV-1 multidrug resistance, 
      which may occur in various genetic contexts, poses a challenging problem in 
      formulating treatment strategies.
CI  - Copyright 2000 Academic Press.
FAU - Tamalet, C
AU  - Tamalet C
AD  - Laboratoire de Virologie, CISIH-Marseille, France.
FAU - Yahi, N
AU  - Yahi N
FAU - Tourres, C
AU  - Tourres C
FAU - Colson, P
AU  - Colson P
FAU - Quinson, A M
AU  - Quinson AM
FAU - Poizot-Martin, I
AU  - Poizot-Martin I
FAU - Dhiver, C
AU  - Dhiver C
FAU - Fantini, J
AU  - Fantini J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Anti-HIV Agents)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*drug therapy
MH  - Anti-HIV Agents/*pharmacology/therapeutic use
MH  - *Genes, MDR
MH  - Genome, Viral
MH  - HIV Reverse Transcriptase/*genetics
MH  - HIV-1/*drug effects/*genetics
MH  - Humans
MH  - Incidence
MH  - *Mutation
EDAT- 2000/05/04 09:00
MHDA- 2000/06/17 09:00
CRDT- 2000/05/04 09:00
PHST- 2000/05/04 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/05/04 09:00 [entrez]
AID - S0042-6822(00)90261-7 [pii]
AID - 10.1006/viro.2000.0261 [doi]
PST - ppublish
SO  - Virology. 2000 May 10;270(2):310-6. doi: 10.1006/viro.2000.0261.