Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc

PLoS One. 2015 May 13;10(5):e0125502. doi: 10.1371/journal.pone.0125502. eCollection 2015.


Objectives: We analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.

Methods: 87 RNA and 60 DNA samples were used. The viral tropism was predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in triplicate, 43 samples with the ESTA assay and 45 with next-generation sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC-resistance mutations on clinical outcome was also studied.

Results: Concordance between single-amplification testing compared to ESTA and to NGS was in the order of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of baseline R5 viruses in RNA and DNA samples by all methods significantly correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC. No influence of the GSS or MVC-resistance mutations but adherence to treatment, on the clinical outcome was detected.

Conclusions: Proviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug. In addition, the new prediction system T-CUP produced reliable results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cyclohexanes / therapeutic use*
  • Female
  • Genes, Viral
  • Genetic Association Studies
  • Genotype
  • HIV Fusion Inhibitors / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Male
  • Maraviroc
  • Middle Aged
  • Treatment Outcome
  • Triazoles / therapeutic use*
  • Viral Tropism / genetics*
  • Young Adult


  • Cyclohexanes
  • HIV Fusion Inhibitors
  • Triazoles
  • Maraviroc

Grants and funding

This work was supported by the RESINA Project (BMG IIA5-2010-2510AUK361), CHAIN Project (EU-223131), EURESIST project (IST-4-027173), MedSys HIV cell entry project (BMBF-0315489C) and CORUS Project (BMBF 01ES0712). The funding sources of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.