| Mutations in the protease gene associated with virological failure to lopinavir/ritonavir-containing regimens. | |
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MedLine Citation:
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PMID: 22431669 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVES: To assess the most frequent resistance-associated mutations (RAMs) to lopinavir/ritonavir in a cohort of patients attended in daily practice. METHODS: We retrospectively identified 195 multitreated subjects with virological failure. Patients were classified as follows: (i) 71 (36.4%) never received lopinavir/ritonavir (lopinavir/ritonavir naive); (ii) 75 (38.5%) had previously failed on lopinavir/ritonavir; and (iii) 49 (25.1%) were on lopinavir/ritonavir at failure. RAM patterns were assessed. Medians, IQRs, percentages, Kruskal-Wallis, χ(2) or Fisher's exact test, and multinomial logistic regression were used whenever appropriate. RESULTS: L10I/F, K20R, L24I, L33F, M36I, M46I/L, I47V, G48V, F53L, I54V, A71V, G73S, V82A, I84V and L90M (all with P ≤ 0.037) were protease RAMs overexpressed in patients with lopinavir/ritonavir failure. L10I, M36I, M46I, I54V, L63P, A71V, V82A, I84V and L90M were the most common in lopinavir/ritonavir-naive patients. Other IAS-USA RAMs for lopinavir/ritonavir (L10R/V, K20M, V32I, I47A, I50V, I54L/A/M/T/S, A71T, L76V and V82F/T/S) were not associated with previous or current failure to lopinavir/ritonavir. Lopinavir/ritonavir failure was associated with the number of protease RAMs (OR = 1.146, 95% CI = 1.287, 1.626), higher exposure to protease inhibitors, and the presence of E44D, L33F, I54V and I84V. CONCLUSIONS: In multitreated patients with previous or current lopinavir/ritonavir failure, some protease mutations are selected at significantly greater rates. L10I, M36I, I54V, L63P, A71V, V82A and L90M were found in >50% of cases. Thus, their presence should be expected when genotypic testing results are not available. The number of protease RAMs and higher prior exposures to protease inhibitors were significantly associated with lopinavir/ritonavir failure. |
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Authors:
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José R Santos; Josep M Llibre; Arkaitz Imaz; Pere Domingo; José A Iribarren; Ana Mariño; Celia Miralles; María J Galindo; Arelly Ornelas; Santiago Moreno; Jonathan M Schapiro; Bonaventura Clotet; |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-19 |
Journal Detail:
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Title: The Journal of antimicrobial chemotherapy Volume: - ISSN: 1460-2091 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7513617 Medline TA: J Antimicrob Chemother Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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