title: Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy.
abstract: BACKGROUND
  HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada.
  
  
  METHODS
  We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of most viral load assays at the time. Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR).
  
  
  RESULTS
  When virologic suppression was defined as two-consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre-therapy R5-virus switched to non-R5 at viral load rebound after a median of 19 months (IQR 8-41 months) of undetectable viremia. Duration of viral load suppression was not a predictor of switch, but lower CD4 count during suppression (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non-R5 HIV by "deep" sequencing (median 0.2% versus 3.2%) were independently associated with switch (p = 0.03 and p<0.0001, respectively).
  
  
  CONCLUSIONS
  R5-to-non-R5 tropism switches in plasma virus after undetectable viremia were relatively rare events especially among patients with higher CD4 counts during virologic suppression. Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.
authors.forename: Guinevere Q
authors.initials: GQ
authors.lastname: Lee
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Winnie
authors.initials: W
authors.lastname: Dong
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Theresa
authors.initials: T
authors.lastname: Mo
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.
authors.forename: David J H F
authors.initials: DJ
authors.lastname: Knapp
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Conan K
authors.initials: CK
authors.lastname: Woods
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Kanters
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Benita
authors.initials: B
authors.lastname: Yip
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D019143:Evolution, Molecular; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012641:Selection, Genetic / Q000187:drug effects; D056189:Viral Tropism / Q000187:drug effects*; D014766:Viremia / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology*