Predictors of virological response to atazanavir in protease inhibitor-experienced patients

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Liste des auteurs: Barrios A, Rendon AL, Gallego O, Martin-Carbonero L, Valer L, Riois P, Maida I, Garcia-Benayas T, Jimenez-Nacher I, Gonzalez-Lahoz J, Soriano V
Editeur: Taylor & Francis: STM, Behavioural Science and Public Health Titles
Année de publication: 2004
Numéro du volume: 5
Numéro de publication: 4
Page d'accueil: 201
Dernière page: 205
Nombre de pages: 5
ISSN: 1528-4336
Languages: Anglais-Royaume-Uni (EN-GB)


Background: Atazanavir (ATV) is the latest approved HIV protease inhibitor (PI). Even though it is very convenient (only two capsules once a day), concerns have risen about its potency.Method: The clinical performance of ATV 400 mg once a day was examined in all PI-experienced patients who were included in the ATV expanded access program conducted in a single institution. The predictive value of baseline drug resistance HIV genotypes, ATV plasma trough levels, and the genotypic inhibitory quotient (GIQ) on the virological response at week 24 was assessed.Results: Data from 92 patients were analyzed. ATV was prescribed as part of a rescue intervention (45%), a simplification strategy (11 %), or an attempt to ameliorate hyperlipidernias (23%) or other toxicities (16%). Tenofovir (TDF) was concomitantly used with ATV in 78% of patients. None received ritonavir boosting. In patients with detectable viremia at baseline (65%), the median HIV RNA drop was 0.7 logs. The median ATV C-min was 0.12 mug/mL (IQR, 0.05-0.22 mug/mL), which is clearly above the IC90 (90% inhibitory concentration) for AT V in wild-type viruses. The virological response did not correlate significantly with ATV C The median number of protease resistance mutations was lower in patients showing virological response than in nonresponders (1 vs. 5; p =.07). A higher HIV RNA drop was associated with a higher GIQ (p =.02; beta = -5.4; 95% Cl, -10 to -1). Only 4 patients (4%) discontinued treatment due to ATV-related toxicities (hyperbilirubinemia in 1). Bilirubin levels were associated with ATV plasma concentrations (p =.05; P = 3.2; 95% CI, -0.1 to 6.5). The rate of hypertriglyceridemia and hypercholesterolemia declined significantly with respect to baseline.Conclusion: ATV is relatively safe and provides significant virological response in PI-experienced patients, mainly among those with a low number of protease resistance mutations. The GIQ predicts accurately the virological response in patients receiving ATV. Hyperbilirubinemia is associated with higher ATV plasma levels.


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