title: Evolution of proviral DNA HIV-1 tropism under selective pressure of maraviroc-based therapy.
abstract: OBJECTIVE
  To evaluate the evolution of HIV-1 coreceptor tropism in proviral DNA of patients during maraviroc-based therapy.
  
  
  METHODS
  Fourteen heavily high active antiretroviral therapy (HAART)-treated patients with a CCR5 Trofile profile were monitored over a 24 month period from the start of maraviroc therapy. Whole-blood samples were obtained at different timepoints, and coreceptor tropism was determined for proviral DNA from the V3-loop region sequence using the Geno2Pheno algorithm [false positive rate (FPR): 20%].
  
  
  RESULTS
  At the start of maraviroc treatment, 13/14 patients were viraemic (median: 4.33 log copies/mL). Concordance in R5 tropism (R5/R5) was observed between circulating HIV-RNA (Trofile) and HIV-DNA provirus in 10/14 patients (median FPR = 54.0%), while 4 patients showed a CXCR4-tropic R5/X4 variant in their provirus (FPR: 5.8%, 5.7%, 16.6% and 1.1%, respectively). All R5/R5 patients showed a stable HIV-1 DNA coreceptor usage. Two out of four R5/X4 patients showed a tropism shift in their archived provirus and, after 6 months a prevalence of R5-tropic virus was detected in DNA. The other two R5/X4 patients harboured the 11/25 genotype, and maintained X4 tropism in provirus during the study. Virological response did not reveal differences in RNA decay and CD4+ cell recovery in patients with discordant tropism.
  
  
  CONCLUSIONS
  A relatively good correlation between RNA and DNA tropism was observed at baseline. Proviral DNA tropism remained stable over 24 months of maraviroc-based therapy, indicating that determination of proviral DNA V3 sequence could be used in tropism prediction in clinical practice. The data also confirm the importance of the 11/25 rule in predicting viral tropism.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy. silvia.baroncelli@iss.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Clementina Maria
authors.initials: CM
authors.lastname: Galluzzo
authors.forename: Liliana Elena
authors.initials: LE
authors.lastname: Weimer
authors.forename: Maria Franca
authors.initials: MF
authors.lastname: Pirillo
authors.forename: Anna
authors.initials: A
authors.lastname: Volpe
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mercuri
authors.forename: Albertina
authors.initials: A
authors.lastname: Cavalli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fragola
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
authors.forename: Anna
authors.initials: A
authors.lastname: Degli Antoni
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.forename: Daniela
authors.initials: D
authors.lastname: Francisci
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bucciardini
authors.forename: Marco
authors.initials: M
authors.lastname: Floridia
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003510:Cyclohexanes / Q000008:administration & dosage* / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D012641:Selection, Genetic; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology; D056189:Viral Tropism
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D014230:Triazoles; D000077592:Maraviroc