Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment.

Cyclohexanes/therapeutic use; Genotype; HIV Infections/drug therapy/metabolism; HIV-1/drug effects/genetics/physiology; Humans; Phenotype; Receptors, CCR5/metabolism; Receptors, CXCR4/metabolism; Triazoles/therapeutic use; Viral Tropism

Abstract :

[en] BACKGROUND: Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care. METHODS: Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call. RESULTS: According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value. CONCLUSIONS: In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.

Disciplines :

Immunology & infectious disease

Author, co-author :

Vandekerckhove, Linos

Verhofstede, Chris

Demecheleer, Els

De Wit, Stephane

Florence, Eric

Fransen, Katrien

Moutschen, Michel ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.

Mostmans, Wendy

Kabeya, Kabamba

Mackie, Nicola

More authors (9 more)

Language :

English

Title :

Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment.

Publication date :

2011

Journal title :

Journal of Antimicrobial Chemotherapy

ISSN :

0305-7453

eISSN :

1460-2091

Publisher :

Oxford University Press, United Kingdom

Volume :

Issue :

Pages :

265-72

Available on ORBi :

since 31 January 2012

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Bibliography

Llibre JM, Schapiro JM, Clotet B. Clinical implications of genotypic resistance to the newer antiretroviral drugs in HIV-1-infected patients with virological failure. Clin Infect Dis 2010; 50: 872-81.
Feeney Eoin R, Mallon Patrick WG. Impact of mitochondrial toxicity of HIV-1 antiretroviral drugs on lipodystrophy and metabolic dysregulation. Curr Pharm Des 2010; in press.
Lang S, Mary-Krause M, Cotte L et al. Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med 2010; 170: 1228-38.
Friis-Moller N, Reiss P, Sabin CA et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356: 1723-35.
Sabin CA, Worm SW, Weber R et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008; 371: 1417-26.
Cormier EG, Dragic T. The crown and stem of the V3 loop play distinct roles in human immunodeficiency virus type 1 envelope glycoprotein interactions with the CCR5 coreceptor. J Virol 2002; 76: 8953-7.
Tsibris AM, Kuritzkes DR. Chemokine antagonists as therapeutics: focus on HIV-1. Annu Rev Med 2007; 58: 445-59.
Whitcomb JM, Huang W, Fransen S et al. Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother 2007; 51: 566-75.
Petropoulos C, Limoli K, Whitcomb J et al. Validation studies defining the performance of Monogram's HIV coreceptor tropism assay. In: Abstracts of the Fifth European HIV Drug Resistance Workshop, Cascais, Portugal, 2007. Abstract 57.
Saag M, Heera J, Goodrich J. Reanalysis of the MERIT study with the enhanced Trofile assay (MERIT-ES). In: Abstracts of the Forty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008. Abstract H-1232a. American Society for Microbiology, Washington, DC, USA.
Van Baelen K, Vandenbroucke I, Rondelez E et al. HIV-1 coreceptor usage determination in clinical isolates using clonal and population-based genotypic and phenotypic assays. J Virol Methods 2007; 146: 61-73.
Vandekerckhove L, Verhofstede C, Vandenbroucke I et al. on behalf of the Tropism Study Group. Comparison of population and 454 genotyping and Trofile phenotyping for tropism determination in patients selected for maraviroc initiation. In: Abstracts of the Eighteenth International HIV Drug Resistance Workshop, Fort Myers, FL, 2009. Abstract 57.
Chan SY, Speck RF, Power C et al. V3 recombinants indicate a central role for CCR5 as a coreceptor in tissue infection by human immunodeficiency virus type 1. J Virol 1999; 73: 2350-8.
Jensen MA, van 't Wout AB. Predicting HIV-1 coreceptor usage with sequence analysis. AIDS Rev 2003; 5: 104-12.
O'Meara D, Wilbe K, Leitner T et al. Monitoring resistance to human immunodeficiency virus type 1 protease inhibitors by pyrosequencing. J Clin Microbiol 2001; 39: 464-73.
Ronaghi M. Pyrosequencing sheds light on DNA sequencing. Genome Res 2001; 11: 3-11.
Shi MM. Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies. Clin Chem 2001; 47: 164-72.
Mitsuya Y, Varghese V, Wang C et al. Minority human immunodeficiency virus type 1 variants in antiretroviral-naive persons with reverse transcriptase codon 215 revertant mutations. J Virol 2008; 82: 10747-55.
Vandekerckhove LPR, Wensing AMJ, Kaiser R et al. Consensus statement of the European guidelines on clinical management of HIV-1 tropism testing. In: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, Scotland, 2010. Abstract O121.
Geretti A, Mackie N. British HIV Association Guidelines on Determining HIV-1 Tropism in Routine Clinical Practice. http://www.bhiva.org/Tropism.aspx (October 2010, date last accessed).
German Recommendations for Determining HIV-1 Coreceptor Usage. http://www.viro.med.uni-erlangen.de/nrz/recommendation080324.pdf (September 2010, date last accessed).
McGovern R, Dong W, Mo T et al. Optimization of clinically relevant cutpoints for the determination of HIV co-receptor usage to predict maraviroc responses in treatment experienced (TE) patients using population V3 genotyping. In: Abstracts of the EACS Conference, Cologne, 2009. Abstract PE3.4/8.
Su Z, Gulick RM, Krambrink A et al. Response to vicriviroc in treatment-experienced subjects, as determined by an enhanced-sensitivity coreceptor tropism assay: reanalysis of AIDS clinical trials group A5211. J Infect Dis 2009; 200:1724-8.
Vandenbroucke I, Van Marck H, Mostmans W et al. HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in phenotypic tropism assays. AIDS Res Ther 2010; 7:4.
Vandenbroucke I, Eygen VV, Rondelez E et al. Minor variant detection at different template concentrations in HIV-1 phenotypic and genotypic tropism testing. Open Virol J 2008; 2: 8-14.
Sing T, Low AJ, Beerenwinkel N et al. Predicting HIV coreceptor usage on the basis of genetic and clinical covariates. Antivir Ther 2007; 12: 1097-106.
Napolitano L, Tressler T, Coakley E et al. Incorporation of optimized primers into the Trofile assay substantially improves determination of viral tropism in genetically diverse HIV subtypes. In: Abstracts of the Forty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, 2009. Abstract 908. American Society for Microbiology, Washington, DC, USA.
Swenson LC, McGovern AR, Dong W et al. Phenotypic screening for HIV tropism versus both population-based and "deep" sequencing. In: Abstracts of the Forty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, 2009. Abstract H-899/378. American Society for Microbiology, Washington, DC, USA.