The lowest X4 Geno2Pheno false-positive rate is associated with greater CD4 depletion in HIV-1 infected patients

Clinical Microbiology and Infection

Volumn 18, Issue 8, 2012, Pages

  Santoro, M M ^a   Armenia, D ^a   Fabeni, L ^b   Santoro, M ^a,c   Gori, C ^b   Forbici, F ^b   Svicher, V ^a   Bertoli, A ^d   Dori, L ^d   Surdo, M ^a   Balestra, E ^a   Palamara, G ^e   Girardi, E ^b   Angarano, G ^f   Andreoni, M ^a,d   Narciso, P ^b   Antinori, A ^b   Ceccherini Silberstein, F ^a   Perno, C F ^a,b,d  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b NATIONAL INSTITUTE FOR INFECTIOUS DISEASES L SPALLANZANI   (Italy)

^c LABORATORIO DI PATOLOGIA VASCOLARE   (Italy)

^d TOR VERGATA UNIVERSITY HOSPITAL   (Italy)

^e SAN GALLICANO DERMATOLOGICAL INSTITUTE   (Italy)

^f UNIVERSITY OF BARI   (Italy)

Author keywords

Advanced HIV 1 infection; CD4 cell count; False positive rate; HIV genotypic tropism; V3 mutations; Viraemia

Indexed keywords

CHEMOKINE RECEPTOR CXCR4; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR; INTEGRASE INHIBITOR; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS RNA;

ADULT; ALGORITHM; ARTICLE; CD4 LYMPHOCYTE COUNT; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE SEVERITY; DRUG TREATMENT FAILURE; FALSE POSITIVE RESULT; FEMALE; GENE MUTATION; GENE SEQUENCE; GENOTYPE; GENOTYPING TECHNIQUE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; TROPISM; VIREMIA; VIRUS LOAD;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84864026622     PISSN: 1198743X     EISSN: 14690691     Source Type: Journal    
DOI: 10.1111/j.1469-0691.2012.03905.x     Document Type: Article

References (29)

1. Jensen MA, Li FS, van't Wout AB et al. Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol 2003; 77: 13376-13388.
2. Berger EA, Doms RW, Fenyö EM et al. A new classification for HIV-1. Nature 1998; 39: 240.
3. Feinberg MB, McCune JM, Miedema F et al. HIV tropism and CD4+ T-cell depletion. Nat Med 2002; 8: 537.
4. Waters L, Mandalia S, Randell P et al. The impact of HIV tropism on decreases in CD4 cell count, clinical progression, and subsequent response to a first antiretroviral therapy regimen. Clin Infect Dis 2008; 46: 1617-1623.
5. Goetz MB, Leduc R, Kostman JR et al. Relationship between HIV coreceptor tropism and disease progression in persons with untreated chronic HIV infection. J Acquir Immune Defic Syndr 2009; 50: 259-266.
6. Raymond S, Delobel P, Mavigner M et al. CXCR4-using viruses in plasma and peripheral blood mononuclear cells during primary HIV-1 infection and impact on disease progression. AIDS 2010; 24: 2305-2312.
7. De Clercq E. The AMD3100 story: the path to the discovery of a stem cell mobilizer (Mozobil). Biochem Pharmacol 2009; 77: 1655-1664.
8. Hendrix CW, Collier AC, Lederman MM et al. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 2004; 37: 1253-1262.
9. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of AntiretroviralAgents in HIV-1-Infected Adults and Adolescents. Available at: (last accessed 30 May 2012).
10. European AIDS Clinical Society. Clinical management and treatment of HIV-infected adults in Europe. Version 6, October 2011. Available at:
11. Vandekerckhove L, Wensing A, Kaiser R et al. European guidelines on the clinical management of HIV-1 tropism testing. Lancet Infect Dis 2011; 11: 394-407.
12. Coakley E, Reeves JD, Huang W et al. Comparison of human immunodeficiency virus type 1 tropism profiles in clinical samples by the Trofile and MT-2 assays. Antimicrob Agents Chemother 2009; 53: 4686-4693.
13. Sing T, Low AJ, Beerenwinkel N et al. Predicting HIV coreceptor usage on the basis of genetic and clinical covariates. Antivir Ther 2007; 12: 1097-1106.
14. Poveda E, Seclen E, Gonzalez MM et al. Design and validation of new genotypic tools for easy and reliable estimation of HIV tropism before using CCR5 antagonists. J Antimicrob Chemother 2009; 63: 1006-1010.
15. Prosperi MC, Bracciale L, Fabbiani M et al. Comparative determination of HIV-1 co-receptor tropism by Enhanced Sensitivity Trofile, gp120V3-loop RNA and DNA genotyping. Retrovirol 2010; 7: 56.
16. Simon B, Grabmeier-Pfistershammer K, Rieger A et al. HIV coreceptor tropism in antiretroviral treatment-naive patients newly diagnosed at a late stage of HIV infection. AIDS 2010; 24: 2051-2058.
17. Svicher V, D'Arrigo R, Alteri C et al. Performance of genotypic tropism testing in clinical practice using the enhanced sensitivity version of Trofile as reference assay: results from the OSCAR Study Group. New Microbiol 2010; 33: 195-206.
18. Wilgenbusch JC, Swofford D. Inferring evolutionary trees with PAUP*. In: Curr Protoc Bioinformatics, Chapter 6, Unit 6.4. 2003.
19. Posada D, Buckley TR. Model selection and model averaging in phylogenetics: advantages of akaike information criterion and bayesian approaches over likelihood ratio tests. Syst Biol 2004; 53: 793-808.
20. Hochberg Y, Benjamini Y. More powerful procedures for multiple significance testing. Stat Med 1990; 9: 811-818.
21. Svicher V, Balestra E, Cento V et al. HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro. Antiviral Res 2011; 90: 42-53.
22. Svicher V, Altreri C, Artese A et al. Identification and structural characterization of novel genetic elements in HIV-1 -V3 loop regulating co-receptor usage. Antivir Ther 2011; 16: 1035-1045.
23. Shimizu N, Haraguchi Y, Takeuchi Y et al. Changes in and discrepancies between cell tropisms and coreceptor uses of human immunodeficiency virus type 1 induced by single point mutations at the V3 tip of the env protein. Virology 1999; 259: 224-333.
24. Briggs D, Tuttle D, Sleasman J, Goodenow M. Envelope V3 amino acid sequence predicts HIV-1 phenotype (co-receptor usage and tropism for macrophages). AIDS 2000; 14: 2937-2939.
25. Hu Q, Trent J, Tomaras G et al. Identification of ENV determinants in V3 that influence the molecular anatomy of CCR5 utilization. J Mol Biol 2000; 302: 359-375.
26. Carrillo A, Ratner L. Human immunodeficiency virus type 1 tropism for T-lymphoid cell lines: role of the V3 loop and C4 envelope determinants. J Virol 1996; 70: 1301-1309.
27. Ross TM, Cullen BR. The ability of HIV type 1 to use CCR-3 as a coreceptor is controlled by envelope V1/V2 sequences acting in conjunction with a CCR-5 tropic V3 loop. Proc Natl Acad Sci 1998; 95: 7682-7686.
28. 3 signatures in the regulation of co-receptor usage. Retrovirol 2011; 12: 8.
29. Poveda E, Briz V, de Mendoza C et al. Prevalence of X4 tropic HIV-1 variants in patients with differences in disease stage and exposure to antiretroviral therapy. J Med Virol 2007; 79: 1040-1046.