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J Infect Dis. 2007 Feb 1;195(3):392-8. Epub 2006 Dec 21.

Phenotypic susceptibility to didanosine is associated with antiviral activity in treatment-experienced patients with HIV-1 infection.

Author information

1
Unité INSERM U720, BP 335-75625, Paris, France. pflandre@ccde.chups.jussieu.fr

Abstract

OBJECTIVE:

We investigated the relationship between human immunodeficiency virus (HIV) phenotypic susceptibility to didanosine and the antiviral activity of didanosine (ddI) in the JAGUAR study.

METHODS:

Baseline plasma HIV phenotypic susceptibility to ddI was assessed using a phenotype assay of patients randomized to receive ddI or placebo for 4 weeks in addition to their current regimen. Phenotypic susceptibility scores (PSSs) were then calculated for each sample. Associations between PSS and week 4 reductions in plasma HIV-1 RNA load or virologic response were assessed using linear regression and Jonckherre's test and the Wilcoxon and Cochran-Armitage tests, respectively.

RESULTS:

In the ddI arm, a significant association between reduction in viral load and continuous PSS was observed (P<.0001). Using distinct categories, an increasing fold change (FC) in susceptibility to ddI was strongly associated with smaller reductions in plasma HIV-1 RNA load (P<.0001). The proportion of virologic responders was 83% (15/18) for patients with a ddI FC < or =1.3, 50% (33/66) for patients with an FC of 1.3-2.2, and 29% (4/14) for patients with an FC > or =2.2 (P=.0008). After we determined these findings, 3 ddI FC categories were defined using 1.3 and 2.2 as thresholds.

CONCLUSIONS:

The relationship between phenotypic susceptibility to ddI and reduction in plasma HIV-1 RNA load describes a continuum. The establishment of a lower clinical cutoff at 1.3 and an upper clinical cutoff at 2.2 are clinically relevant.

PMID:
17205478
DOI:
10.1086/510754
[Indexed for MEDLINE]

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