Journal Article

Analysis of protease inhibitor combinations <i>in vitro</i>: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates

Elisabetta Bulgheroni, Paola Citterio, Francesco Croce, Mirko Lo Cicero, Ottavia Viganò, Francesca Soster, Ting-Chao Chou, Massimo Galli and Stefano Rusconi

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 3, pages 464-468
Published in print March 2004 | ISSN: 0305-7453
Published online March 2004 | e-ISSN: 1460-2091 | DOI:
Analysis of protease inhibitor combinations in vitro: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates

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Background: Despite the increasing number of antiretroviral compounds, the number of useful drug regimens is limited owing to the high frequency of cross-resistance.

Patients and methods: 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).

Results: In 14aPre experiments, the combination tipranavir + lopinavir demonstrated synergy at low concentrations (IC50), an additive effect at IC75 and antagonism at IC90–IC95; tipranavir + amprenavir were antagonistic at all concentrations except IC95, 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 IC95.

Conclusions: 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 IC95 in infections by a wild-type isolate.

Keywords: Keywords: HIV-1, protease inhibitors, in vitro combinations, drug resistance, combination index

Journal Article.  3945 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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