PMID- 16308226
OWN - NLM
STAT- MEDLINE
DCOM- 20060125
LR  - 20091119
IS  - 0036-5548 (Print)
IS  - 0036-5548 (Linking)
VI  - 37
IP  - 11-12
DP  - 2005
TI  - Genetic evolution of HIV in patients remaining on a stable HAART regimen despite 
      insufficient viral suppression.
PG  - 890-901
AB  - Our objective was to investigate whether steadily increasing resistance levels 
      are inevitable in the course of a failing but unchanged Highly Active 
      Antiretroviral Therapy (HAART) regimen. Patients having an unchanged HAART 
      regimen and a good CD4 response (100 cells/microl above nadir) despite consistent 
      HIV-RNA levels above 200 copies/ml were included in the study. The study period 
      spanned at least 12 months and included 47 plasma samples from 17 patients that 
      were sequenced and analysed with respect to evolutionary changes. At inclusion, 
      the median CD4 count was 300 cells/ml (inter-quartile range (IQR): 231-380) and 
      the median HIV-RNA was 2000 copies/ml (IQR: 1301-6090). Reverse transcription 
      inhibitor (RTI) mutations increased 0.5 mutations per y (STD = 0.8 mutations per 
      y), while major protease inhibitor (PI) resistance mutations increased at a rate 
      of 0.2 mutations per y (STD = 0.8 mutations per y) and minor PI resistance 
      mutations increased at a rate of 0.3 mutations per y (STD = 0.7 mutations per y). 
      The rate at which RTI mutations accumulated decreased during the study period (p 
      = 0.035). Interestingly, the rate of mutation accumulation was not associated 
      with HIV-RNA level. The majority of patients kept accumulating new resistance 
      mutations. However, 3 out of 17 patients with viral failure were caught in an 
      apparent mutational deadlock, thus the development of additional resistance 
      during a failing HAART is not inevitable. We hypothesize that certain patterns of 
      mutations can cause a mutational deadlock where the evolutionary benefit of 
      further resistance mutation is limited if the patient is kept on a stable HAART 
      regimen.
FAU - Kristiansen, Thomas B
AU  - Kristiansen TB
AD  - Centre for Biological Sequence Analysis, Technical University of Denmark, 
      Copenhagen, Denmark. ThomasBirk@Dadlnet.dk
FAU - Pedersen, Anders G
AU  - Pedersen AG
FAU - Eugen-Olsen, Jesper
AU  - Eugen-Olsen J
FAU - Katzenstein, Terese L
AU  - Katzenstein TL
FAU - Lundgren, Jens D
AU  - Lundgren JD
LA  - eng
PT  - Journal Article
PL  - England
TA  - Scand J Infect Dis
JT  - Scandinavian journal of infectious diseases
JID - 0215333
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Adult
MH  - *Antiretroviral Therapy, Highly Active
MH  - CD4 Lymphocyte Count
MH  - Cohort Studies
MH  - Drug Resistance, Viral/genetics
MH  - Evolution, Molecular
MH  - Female
MH  - Genes, Viral
MH  - Genotype
MH  - HIV Infections/*drug therapy/immunology/*virology
MH  - HIV-1/*drug effects/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Phylogeny
MH  - RNA, Viral/blood/genetics
MH  - Selection, Genetic
MH  - Time Factors
MH  - Treatment Failure
EDAT- 2005/11/26 09:00
MHDA- 2006/01/26 09:00
CRDT- 2005/11/26 09:00
PHST- 2005/11/26 09:00 [pubmed]
PHST- 2006/01/26 09:00 [medline]
PHST- 2005/11/26 09:00 [entrez]
AID - NPX228712235X037 [pii]
AID - 10.1080/00365540500333491 [doi]
PST - ppublish
SO  - Scand J Infect Dis. 2005;37(11-12):890-901. doi: 10.1080/00365540500333491.