Tipranavir (TPV) genotypic inhibitory quotient predicts virological response at 48 weeks to TPV-based salvage regimens
| Autor: | Mauro Sciandra, Lorena Baietto, Daniel Gonzalez de Requena, Antonio D'Avolio, Silvia Garazzino, Stefano Bonora, L. Trentini, Giovanni Di Perri, Silvia Fontana, Marco Siccardi, Maria Grazia Milia, Antonio Di Garbo, Andrea Calcagno |
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| Rok vydání: | 2007 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Enfuvirtide Genotype Anti-HIV Agents Pyridines Salvage therapy Fosamprenavir HIV Infections Microbial Sensitivity Tests Biology Antiviral Agents HIV Protease Predictive Value of Tests Internal medicine Drug Resistance Viral medicine Humans Pharmacology (medical) Pharmacology Salvage Therapy Sulfonamides Ritonavir Lopinavir HIV Protease Inhibitors Middle Aged Regimen Infectious Diseases Treatment Outcome Pyrones Immunology HIV-1 Reverse Transcriptase Inhibitors Drug Therapy Combination Female Tipranavir Viral load medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 52(3) |
| ISSN: | 0066-4804 |
| Popis: | Tipranavir (TPV) is a nonpeptidic protease inhibitor with potent in vitro activity against most human immunodeficiency virus (HIV) type 1 (HIV-1) strains resistant to other protease inhibitors (PIs) (1, 14, 15). In vitro data have shown that resistance to TPV develops slowly (5). When TPV is coadministered with ritonavir (RTV) as a booster, TPV has been shown to have potent antiviral activity in multidrug-experienced patients (3, 6, 9, 12). In the RESIST-1 and the RESIST-2 studies, the efficacy and safety of TPV-RTV (500 mg/200 mg twice daily) in 1,509 highly treatment-experienced HIV-1-positive patients were assessed. Analysis at 48 weeks showed that the TPV-RTV-containing regimens significantly improved the immune and virological responses (VRs) compared to the responses to an RTV-boosted comparator PI plus an optimized background (OB) regimen (3, 6, 8). Different factors have been found to be associated with the virological and immunological responses: a lower viral load (VL) at the baseline, the use of enfuvirtide (T20) as a part of the OB regimen, the presence of two or more active drugs in the OB regimen (OB score [OBS], ≥2) (3, 6, 8), and the baseline numbers of specific TPV-associated resistance mutations (TPV RMs) (2). Moreover, the TPV trough concentration (Ctrough) and phenotypic inhibitory quotient (IQ) have also been shown to be associated with the VR at week 24 (12a, 16). The genotypic IQ (gIQ), which is the ratio between the PI Ctrough and the number of PI-associated mutations, is simpler to derive than the IQ in the clinical setting. The gIQ has previously been shown to be a predictor of the therapeutic response to PI-based salvage regimens, e.g., lopinavir or fosamprenavir (7, 10, 11, 13). Preliminary data showed that TPV-gIQ correlated with the early and the middle VRs (2a, 2b). However, no data are yet available on the predictive value of the TPV gIQ on the long-term efficacy of TPV-based regimens. Therefore, the aim of our study was to perform a pharmacokinetic/pharmacodynamic evaluation of the predictors of the VR at week 48 to salvage TPV-containing regimens in the clinical setting. |
| Databáze: | OpenAIRE |
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