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2 results on '"genotypic resistance tests"'

1. Mutations in the protease gene associated with virological failure to lopinavir/ritonavir-containing regimens.

Author

Santos, José R., Llibre, Josep M., Imaz, Arkaitz, Domingo, Pere, Iribarren, José A., Mariño, Ana, Miralles, Celia, Galindo, María J., Ornelas, Arelly, Moreno, Santiago, Schapiro, Jonathan M., and Clotet, Bonaventura

Subjects
*LOPINAVIR-ritonavir, *VIROLOGY, *SALVAGE therapy, *THERAPEUTICS, *CANCER treatment
Abstract

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, χ2 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. [ABSTRACT FROM PUBLISHER]

Published
2012

2. Mutations in the protease gene associated with virological failure to lopinavir/ritonavir-containing regimens

Author

Josep M. Llibre, Arelly Ornelas, Jonathan M. Schapiro, María José Galindo, Pere Domingo, Ana Mariño, Arkaitz Imaz, Santiago Moreno, Celia Miralles, José Antonio Iribarren, Bonaventura Clotet, and José R. Santos

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, resistance-associated mutations, Anti-HIV Agents, medicine.medical_treatment, Mutation, Missense, Lopinavir/ritonavir, HIV Infections, Gastroenterology, Lopinavir, Cohort Studies, HIV Protease, immune system diseases, Internal medicine, medicine, Humans, Pharmacology (medical), Treatment Failure, salvage therapy, Retrospective Studies, Pharmacology, Protease, Ritonavir, business.industry, Proteolytic enzymes, virus diseases, HIV, biochemical phenomena, metabolism, and nutrition, Virological failure, Virology, United States, Exact test, Infectious Diseases, genotypic resistance tests, Amino Acid Substitution, Female, business, Protease Gene, medicine.drug
Abstract

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.

Published
2012

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