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

Details

Serval ID
serval:BIB_48F2088F8B2C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy
Journal
Aids
Author(s)
Weiser Barbara, Philpott Sean, Klimkait Thomas, Burger Harold, Kitchen Christina, Buergisser Philippe, Gorgievski Meri, Perrin Luc., Piffaretti Jean-Claude, Ledergerber Bruno
ISSN
0269-9370
Publication state
Published
Issued date
2008
Volume
22
Number
4
Pages
469-479
Language
english
Abstract
Background: Although combination antiretroviral therapy (cART) dramatically reduces rates of AIDS and death, a minority of patients experience clinical disease progression during treatment. <p>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/mu l; P= 0.012). The adjusted multivariable hazard ratio (HR) for clinical progression was 4.8 [95% confidence interval (Cl) 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%Cl, 1.2-11.3) and 5.9 (95% Cl, 2.2-15.0) for baseline loads of 2.2-4.3 and > 4.3 log(10)copies/ml, respectively, compared with < 2.2 log(10)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.
Keywords
aIDS, antiretroviral therapy, CCR5, CXCR4, heteroduplex tracking assay, HIV-1 tropism, Immunodeficiency-Virus Type-1, Syncytium-Inducing Phenotype, In-Vivo Evolution, Cd4 Cell Count, V3 Loop, Virological Failure, Infected Patients, Hiv-1-Infected Individuals, Prognostic Importance, Genital-Tract
Web of science
Create date
13/10/2009 11:56
Last modification date
20/08/2019 13:56
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