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- Title
Analysis of protease inhibitor combinations in vitro: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates.
- Authors
Bulgheroni, Elisabetta; Citterio, Paola; Croce, Francesco; Lo Cicero, Mirko; Viganò, Ottavia; Soster, Francesca; Chou, Ting-Chao; Galli, Massimo; Rusconi, Stefano
- Abstract
<bold>Background: </bold>Despite the increasing number of antiretroviral compounds, the number of useful drug regimens is limited owing to the high frequency of cross-resistance.<bold>Patients and Methods: </bold>We studied in vitro two-drug combinations using three protease inhibitors (PIs), tipranavir, amprenavir and lopinavir, on isolates (003 and 004) derived from patients with resistance to multiple PIs compared with the drug-susceptible isolate 14aPre in peripheral blood mononuclear cells. Drug interactions were determined by median dose-effect analysis, with the combination index calculated at several inhibitory concentrations (IC).<bold>Results: </bold>In 14aPre experiments, the combination tipranavir + lopinavir demonstrated synergy at low concentrations (IC(50)), an additive effect at IC(75) and antagonism at IC(90)-IC(95); tipranavir + amprenavir were antagonistic at all concentrations except IC(95), where they were synergic; and the lopinavir + amprenavir combination was always antagonistic. In 003 and 004 infections, tipranavir + lopinavir and tipranavir + amprenavir combinations were antagonistic, and lopinavir + amprenavir were synergic, at all concentrations, with the exception of being additive at IC(95).<bold>Conclusions: </bold>Our in vitro experiments did not show any advantage in combining second generation PIs as a therapeutic strategy in naive or multi-treatment failure subjects, with the exception of tipranavir + amprenavir at IC(95) in infections by a wild-type isolate.
- Subjects
COMPARATIVE studies; DRUG resistance in microorganisms; ENZYME-linked immunosorbent assay; HETEROCYCLIC compounds; HIV; HIV infections; RESEARCH methodology; MEDICAL cooperation; PYRIDINE; RESEARCH; RNA; SULFONAMIDES; EVALUATION research; ACYCLIC acids; HIV protease inhibitors; GENOTYPES; PHARMACODYNAMICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2004, Vol 53, Issue 3, p464
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkh103