PMID- 19864933
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20211020
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 24
IP  - 3
DP  - 2010 Jan 28
TI  - Development of a didanosine genotypic resistance interpretation system based on 
      large derivation and validation datasets.
PG  - 365-71
LID - 10.1097/QAD.0b013e32833338ba [doi]
AB  - OBJECTIVE: To assess the genotypic determinants of the virological response to 
      didanosine (ddI) in HIV-infected patients. METHODS: The Forum database on ddI was 
      randomly divided into a derivation set (n = 1000) and a validation set (n = 453). 
      Linear regression models and bootstrap sampling were used to select resistance 
      mutations and to estimate their resistance scores. Linear regression models, 
      accounted for the censoring of viral load measurements due to assay lower limits, 
      of the week 8 reduction in viral load from baseline were adjusted for baseline 
      viral load, the exact number of weeks between baseline and the week 8 viral load 
      measurements, and the Stanford genotypic sensitivity score. RESULTS: The ddI 
      resistance mutations and their resistance scores based on the derivation set were 
      as follows: M41L (score of 14), T69D (24), D123S (40), T139M (54), I180V (53), 
      M184V (-12), V189I (55), Q207K (37), L210W (25), and T215Y (eight). The total 
      score is obtained by adding the individual scores. Viruses with scores of 19 or 
      less, 20-59, and 60 or more are considered sensitive, intermediate, and 
      resistant, respectively. In the validation set, respectively, 58.7, 36.9, and 
      4.4% of viruses were predicted to be sensitive, intermediate, and resistant to 
      ddI. The observed viral load reductions at week 8 were, respectively, 1.51 log10 
      copies/ml [interquartile range (IQR) 1.26-1.76] (P = 0.0001 versus resistant), 
      1.11 (0.94-1.30) (P = 0.0077 versus sensitive), and 0.46 (0.32-0.74) (P = 0.0079 
      versus intermediate). CONCLUSION: We developed a genotypic resistance score for 
      didanosine including four mutations never previously used.
FAU - Assoumou, Lambert
AU  - Assoumou L
AD  - INSERM U943, UPMC Univ Paris 06, UMR S 943, Paris, France.
FAU - Cozzi-Lepri, Alessandro
AU  - Cozzi-Lepri A
FAU - Brun-Vezinet, Francoise
AU  - Brun-Vezinet F
FAU - Degruttola, Victor
AU  - Degruttola V
FAU - Kuritzkes, Daniel R
AU  - Kuritzkes DR
FAU - Phillips, Andrew
AU  - Phillips A
FAU - Zolopa, Andrew
AU  - Zolopa A
FAU - Miller, Veronica
AU  - Miller V
FAU - Flandre, Philippe
AU  - Flandre P
FAU - Costagliola, Dominique
AU  - Costagliola D
CN  - Standardization, Clinical Relevance of HIV Drug Resistance Testing Project from 
      the Forum for Collaborative HIV Research
LA  - eng
GR  - G0900274/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Anti-HIV Agents)
RN  - 0 (RNA, Viral)
RN  - K3GDH6OH08 (Didanosine)
SB  - IM
MH  - Adult
MH  - Algorithms
MH  - Anti-HIV Agents/*pharmacology
MH  - Didanosine/*pharmacology
MH  - Drug Resistance, Viral/*genetics
MH  - Female
MH  - Genotype
MH  - HIV Infections/*drug therapy/genetics/virology
MH  - HIV-1/*drug effects/genetics
MH  - Humans
MH  - Linear Models
MH  - Male
MH  - Middle Aged
MH  - *Mutation/genetics
MH  - RNA, Viral/genetics
MH  - Viral Load
FIR - Ribaudo, H
IR  - Ribaudo H
FIR - Bohlin, P
IR  - Bohlin P
FIR - Wantman, M
IR  - Wantman M
FIR - Masquelier, B
IR  - Masquelier B
FIR - Zazzi, M
IR  - Zazzi M
FIR - Hogg, B
IR  - Hogg B
FIR - Harrigan, R
IR  - Harrigan R
FIR - Lundgren, J
IR  - Lundgren J
FIR - Kjaer, J
IR  - Kjaer J
FIR - d'Arminio Monforte, A
IR  - d'Arminio Monforte A
FIR - Gatell, J
IR  - Gatell J
FIR - Perez, M J
IR  - Perez MJ
FIR - Seekins, D
IR  - Seekins D
FIR - Costagliola, D
IR  - Costagliola D
FIR - Brun-Vezinet, F
IR  - Brun-Vezinet F
FIR - Ledergerber, B
IR  - Ledergerber B
FIR - Shafer, R
IR  - Shafer R
FIR - De Luca, A
IR  - De Luca A
FIR - Pillay, D
IR  - Pillay D
FIR - Dunn, D
IR  - Dunn D
FIR - Sabin, C
IR  - Sabin C
EDAT- 2009/10/30 06:00
MHDA- 2011/01/11 06:00
CRDT- 2009/10/30 06:00
PHST- 2009/10/30 06:00 [entrez]
PHST- 2009/10/30 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
AID - 10.1097/QAD.0b013e32833338ba [doi]
PST - ppublish
SO  - AIDS. 2010 Jan 28;24(3):365-71. doi: 10.1097/QAD.0b013e32833338ba.