Document Detail


Mutations in the protease gene associated with virological failure to lopinavir/ritonavir-containing regimens.
MedLine Citation:
PMID:  22431669     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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;
Related Documents :
19480249 - Risk of malignancy index for adnexal masses.
8445059 - Immunophenotypic and genotypic analysis in cutaneous lymphoid hyperplasias.
9836059 - Treatment of lichen planus and lichen nitidus with itraconazole: reports of six cases.
1761349 - Spleen cell dialyzable extracts (scde) mediated immunotherapy for patients with myasthe...
20859119 - Caspr2 antibodies in patients with thymomas.
10987869 - Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid.
11576629 - Histological insight into the pathogenesis of severe laryngomalacia.
12730539 - Progression of peripheral joint disease in psoriatic arthritis: a 5-yr prospective study.
20189159 - Topical mecamylamine for diabetic macular edema.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-19
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  -     ISSN:  1460-2091     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Are intracostal sutures better than pericostal sutures for closing a thoracotomy?
Next Document:  Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses o...