Analysis of protease inhibitor combinations in vitro: Activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates Journal Article
| Authors: | Bulgheroni, E.; Citterio, P.; Croce, F.; Lo Cicero, M.; Viganò, O.; Soster, F.; Chou, T. C.; Galli, M.; Rusconi, S. |
| Article Title: | Analysis of protease inhibitor combinations in vitro: Activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates |
| Abstract: | 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. © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved. |
| Keywords: | controlled study; hydroxyurea; drug potentiation; nonhuman; pyridines; human immunodeficiency virus infection; protease inhibitors; genotype; in vitro study; drug resistance; pyrimidinones; wild type; drug antagonism; mononuclear cell; sulfonamides; enzyme-linked immunosorbent assay; drug sensitivity; proteinase inhibitor; concentration response; multidrug resistance; carbamates; hiv infections; rna, viral; human immunodeficiency virus 1; drug resistance, viral; hiv-1; zidovudine; lamivudine; virus isolation; ritonavir; saquinavir; didanosine; abacavir; amprenavir; efavirenz; combination index; hiv protease inhibitors; nevirapine; pyrones; humans; human; article; in vitro combinations; lopinavir; tipranavir; zalcitabine |
| Journal Title: | Journal of Antimicrobial Chemotherapy |
| Volume: | 53 |
| Issue: | 3 |
| ISSN: | 0305-7453 |
| Publisher: | Oxford University Press |
| Date Published: | 2004-03-01 |
| Start Page: | 464 |
| End Page: | 468 |
| Language: | English |
| DOI: | 10.1093/jac/dkh103 |
| PROVIDER: | scopus |
| PUBMED: | 14963061 |
| DOI/URL: | |
| Notes: | J. Antimicrob. Chemother. -- Cited By (since 1996):21 -- Export Date: 16 June 2014 -- CODEN: JACHD -- Source: Scopus |
