Tropism Testing in the Clinical Management of HIV-1 Infection

Overview

Journal Curr Opin HIV AIDS

Specialty Infectious Diseases

Date 2010 Jan 6

PMID 20048714

Citations 12

Authors

Nina H Lin

Daniel R Kuritzkes

Affiliations

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Abstract

Purpose Of Review: A variety of methods are available to determine HIV-1 co-receptor usage, commonly referred to as viral tropism. This article reviews recent data on phenotypic and genotypic assays of HIV-1 tropism.

Recent Findings: Tropism assays are used to determine co-receptor usage of HIV-1 in patients who may be candidates for treatment with CCR5 antagonists. Phenotypic assays are used most often in the clinical trials of CCR5 antagonists, and are considered the 'gold standard' for comparison with other methods of tropism testing. Enhancements have allowed detection of a lower threshold of minor CXCR4-using species. When compared with phenotypic assays, genotypic methods have poor sensitivity but good specificity at detecting CXCR4-using HIV-1. Preliminary results from a recent comparative study suggest that some genotypic methods may perform as well as phenotypic tests in predicting virologic response to CCR5 antagonists. Several studies show that tropism testing may provide useful prognostic information regarding the risk of disease progression.

Summary: Understanding the characteristic of different tropism assays is important for their clinical use. Although phenotypic testing currently is favored, genotypic assays may be a suitable alternative in appropriate settings.

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References

Garrido C, Roulet V, Chueca N, Poveda E, Aguilera A, Skrabal K . Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes. J Clin Microbiol. 2008; 46(3):887-91. PMC: 2268339. DOI: 10.1128/JCM.01611-07. View

Weber J, Piontkivska H, Quinones-Mateu M . HIV type 1 tropism and inhibitors of viral entry: clinical implications. AIDS Rev. 2006; 8(2):60-77. View

Gulick R, Su Z, Flexner C, Hughes M, Skolnik P, Wilkin T . Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. J Infect Dis. 2007; 196(2):304-12. DOI: 10.1086/518797. View

Weiser B, Philpott S, Klimkait T, Burger H, Kitchen C, Burgisser P . HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy. AIDS. 2008; 22(4):469-79. DOI: 10.1097/QAD.0b013e3282f4196c. View

Jensen M, Coetzer M, van t Wout A, Morris L, Mullins J . A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on envelope V3 sequences. J Virol. 2006; 80(10):4698-704. PMC: 1472078. DOI: 10.1128/JVI.80.10.4698-4704.2006. View

Fouchier R, Groenink M, Kootstra N, Tersmette M, Huisman H, Miedema F . Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol. 1992; 66(5):3183-7. PMC: 241084. DOI: 10.1128/JVI.66.5.3183-3187.1992. View

Pillai S, Good B, Richman D, Corbeil J . A new perspective on V3 phenotype prediction. AIDS Res Hum Retroviruses. 2003; 19(2):145-9. DOI: 10.1089/088922203762688658. View

Schuitemaker H, Koot M, Kootstra N, Dercksen M, de Goede R, van Steenwijk R . Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol. 1992; 66(3):1354-60. PMC: 240857. DOI: 10.1128/JVI.66.3.1354-1360.1992. View

Jensen M, van t Wout A . Predicting HIV-1 coreceptor usage with sequence analysis. AIDS Rev. 2003; 5(2):104-12. View

10.

Wilkin T, Su Z, Kuritzkes D, Hughes M, Flexner C, Gross R . HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis. 2007; 44(4):591-5. DOI: 10.1086/511035. View

11.

Waters L, Mandalia S, Randell P, Wildfire A, Gazzard B, Moyle G . 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(10):1617-23. DOI: 10.1086/587660. View

12.

Tsibris A, Kuritzkes D . Chemokine antagonists as therapeutics: focus on HIV-1. Annu Rev Med. 2006; 58:445-59. DOI: 10.1146/annurev.med.58.080105.102908. View

13.

de Roda Husman A, Koot M, Cornelissen M, Keet I, Brouwer M, Broersen S . Association between CCR5 genotype and the clinical course of HIV-1 infection. Ann Intern Med. 1998; 127(10):882-90. DOI: 10.7326/0003-4819-127-10-199711150-00004. View

14.

Fatkenheuer G, Nelson M, Lazzarin A, Konourina I, Hoepelman A, Lampiris H . Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med. 2008; 359(14):1442-55. DOI: 10.1056/NEJMoa0803154. View

15.

Hunt P, Harrigan P, Huang W, Bates M, Williamson D, McCune J . Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients with detectable viremia. J Infect Dis. 2006; 194(7):926-30. DOI: 10.1086/507312. View

16.

Brumme Z, Goodrich J, Mayer H, Brumme C, Henrick B, Wynhoven B . Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis. 2005; 192(3):466-74. DOI: 10.1086/431519. View

17.

Delobel P, Sandres-Saune K, Cazabat M, Pasquier C, Marchou B, Massip P . R5 to X4 switch of the predominant HIV-1 population in cellular reservoirs during effective highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2005; 38(4):382-92. DOI: 10.1097/01.qai.0000152835.17747.47. View

18.

Saag M, Goodrich J, Fatkenheuer G, Clotet B, Clumeck N, Sullivan J . A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009; 199(11):1638-47. DOI: 10.1086/598965. View

19.

Koot M, Keet I, Vos A, de Goede R, Roos M, Coutinho R . Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993; 118(9):681-8. DOI: 10.7326/0003-4819-118-9-199305010-00004. View

20.

Goetz M, Leduc R, Kostman J, Labriola A, Lie Y, Weidler J . Relationship between HIV coreceptor tropism and disease progression in persons with untreated chronic HIV infection. J Acquir Immune Defic Syndr. 2009; 50(3):259-66. PMC: 2670851. DOI: 10.1097/QAI.0b013e3181989a8b. View