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HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy

Weiser, B. and Philpott, S. and Klimkait, T. and Burger, H. and Kitchen, C. and Bürgisser, P. and Gorgievski, M. and Perrin, L. and Piffaretti, J. C. and Ledergerber, B. and Swiss, HIV Cohort Study. (2008) HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy. AIDS, Vol. 22. pp. 469-479.

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Official URL: http://edoc.unibas.ch/dok/A6003504

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Abstract

BACKGROUND: Although combination antiretroviral therapy (cART) dramatically reduces rates of AIDS and death, a minority of patients experience clinical disease progression during treatment. OBJECTIVE: To investigate whether detection of CXCR4(X4)-specific strains or quantification of X4-specific HIV-1 load predict clinical outcome. METHODS: From the Swiss HIV Cohort Study, 96 participants who initiated cART yet subsequently progressed to AIDS or death were compared with 84 contemporaneous, treated nonprogressors. A sensitive heteroduplex tracking assay was developed to quantify plasma X4 and CCR5 variants and resolve HIV-1 load into coreceptor-specific components. Measurements were analyzed as cofactors of progression in multivariable Cox models adjusted for concurrent CD4 cell count and total viral load, applying inverse probability weights to adjust for sampling bias. RESULTS: Patients with X4 variants at baseline displayed reduced CD4 cell responses compared with those without X4 strains (40 versus 82 cells/microl; P = 0.012). The adjusted multivariable hazard ratio (HR) for clinical progression was 4.8 [95% confidence interval (CI) 2.3-10.0] for those demonstrating X4 strains at baseline. The X4-specific HIV-1 load was a similarly independent predictor, with HR values of 3.7 (95% CI, 1.2-11.3) and 5.9 (95% CI, 2.2-15.0) for baseline loads of 2.2-4.3 and < 4.3 log10 copies/ml, respectively, compared with > 2.2 log10 copies/ml. CONCLUSIONS: HIV-1 coreceptor usage and X4-specific viral loads strongly predicted disease progression during cART, independent of and in addition to CD4 cell count or total viral load. Detection and quantification of X4 strains promise to be clinically useful biomarkers to guide patient management and study HIV-1 pathogenesis.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Molecular Virology (Klimkait)
UniBasel Contributors:Klimkait, Thomas
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Current Science
ISSN:0269-9370
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:22
Deposited On:08 Nov 2012 16:09

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