Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice

Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with impr...

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Bibliographic Details
Published in:	Clinical microbiology and infection Vol. 18; no. 6; pp. 606 - 612
Main Authors:	Symons, J., Vandekerckhove, L., Paredes, R., Verhofstede, C., Bellido, R., Demecheleer, E., van Ham, P.M., van Lelyveld, S.F.L., Stam, A.J., van Versendaal, D., Nijhuis, M., Wensing, A.M.J.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Elsevier Ltd 01-06-2012 Blackwell Publishing Ltd Wiley-Blackwell Elsevier Limited
Subjects:	Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences CCR5 Clinical Laboratory Techniques - methods Clinical medicine CXCR4 Genotype genotypic HIV HIV Infections - virology HIV-1 HIV-1 - genetics HIV-1 - isolation & purification HIV-1 - pathogenicity Human immunodeficiency virus Human immunodeficiency virus 1 Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology Infectious diseases maraviroc Medical research Medical sciences Pharmacology. Drug treatments R5-tropic RNA, Viral - genetics Sequence Analysis, DNA - methods tropism Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Tropism Virology - methods X4-tropic HIV-1 maraviroc X4-tropic genotypic tropism CXCR4 CCR5 R5-tropic Tropism Immunopathology Antiretroviral agent HIV-1 virus Retroviridae HIV-I Genotype AIDS Immune deficiency Lentivirus Infection Virus CCR5 chemokine receptor Maraviroc Viral disease Antiviral Human immunodeficiency virus Predictive factor CXCR4 chemokine receptor
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Summary:	Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with improved prediction of virological response by increasing the detection of X4-tropic variants. Our objective was to evaluate the impact of triplicate genotypic analysis on prediction of co-receptor usage in routine clinical practice. Samples from therapy-naive and therapy-experienced patients were collected for routine tropism testing at three European clinical centres. Viral RNA was isolated from plasma and proviral DNA from peripheral blood mononuclear cells. Gp120-V3 was amplified in a triplicate nested RT-PCR procedure and sequenced. Co-receptor usage was predicted using the Geno2Pheno[coreceptor] algorithm and analysed with a false-positive rate (FPR) of 5.75%, 10%, or an FPR of 20% and according to the current European guidelines on the clinical management of HIV-1 tropism testing. A total of 266 sequences were obtained from 101 patient samples. Discordance in tropism prediction for the triplicates was observed in ten samples using an FPR of 10%. Triplicate testing resulted in a 16.7% increase in X4-predicted samples and to reclassification from R5 to X4 tropism for four cases rendering these patients ineligible for Maraviroc treatment. In conclusion, triplicate genotypic tropism testing increases X4 tropism detection in individual cases, which may prove to be pivotal when CCR5-inhibitor therapy is applied.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1198-743X 1469-0691
DOI:	10.1111/j.1469-0691.2011.03631.x