In:
Antiviral Therapy, SAGE Publications, Vol. 13, No. 2 ( 2008-02), p. 271-280
Abstract:
We assessed the association of baseline HIV-1 mutations, phenotypic sensitivity and pharmacokinetics with virological failure (VF) at week 12 (W12) after onset of a darunavir/ritonavir (DRV/r)-based regimen in a cohort of 67 antiretroviral-experienced HIV-patients failing on highly active antiretroviral therapy (HAART). Methods VF was defined as HIV RNA 〉 2.3 log 10 copies/ml at W12. HIV reverse transcriptase and protease sequencing was performed at W0; mutations with a P-value 〈 0.25 in univariable analyses were used for a backward selection to find the best mutation set for VF prediction. Genotypic and phenotypic sensitivity scores were calculated and virtual phenotype predicted fold change (FC) assessed. DRV C min , C max , AUC 0→12 h and genotypic inhibitory quotient (GIQ) were determined. Results Patients had a median of 15 previous treatments for 10 years. Median W0 values included a T-cell count of 129 cells/μl, 4.7 log 10 HIV RNA copies/ml, four major protease and six nucleoside reverse transcriptase inhibitor resistance mutations. At W12, median HIV RNA decrease was -2.1 log 10 copies/ml with a gain of +67 CD4 + T-cells/μl; 40% of patients failed. We determined the genotypic score I13V+V32I+L33F/I/V+E35D+ M36I/L/V+I47V+F53L+I62V According to 〈 4, 4–5 and 〉 5 mutations, failure occurred in 11%, 48% and 100% of patients. Failure was associated with CDC stage, baseline CD4 + T-cell count, number of major protease inhibitor resistance mutations, FC and DRV/r score. Pharmacokinetics were not associated with failure, but GIQ was. Conclusion At W12, 60% of heavily pretreated patients responded on DRV/r-based HAART. Genotypic and phenotypic information constituted the main virological response determinant in patients with optimal drug concentrations.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
DOI:
10.1177/135965350801300214
Language:
English
Publisher:
SAGE Publications
Publication Date:
2008
detail.hit.zdb_id:
2118396-X
SSG:
15,3
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