Objectives: Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients. Methods: An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10000, 10001-100000 and >100000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients. Results: Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10000 = 53.7%; 10001-100000 = 30.0%; and >100000 = 30.8%). At viraemia <= 500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL. Conclusions: Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.
HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia / D. Armenia, L. Fabeni, C. Alteri, D. Di Pinto, D. Di Carlo, A. Bertoli, C. Gori, S. Carta, V. Fedele, F. Forbici, R. D'Arrigo, V. Svicher, G. Berno, D. Pizzi, E. Nicastri, L. Sarmati, C. Pinnetti, A. Ammassari, G. D'Offizi, A. Latini, M. Andreoni, A. Antinori, F. Ceccherini-Silberstein, C. Perno, M. Santoro. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 70:6(2015 Jun), pp. 1865-1873.
HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia
C. Alteri;D. Di Carlo;C. PernoPenultimo
;
2015
Abstract
Objectives: Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients. Methods: An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10000, 10001-100000 and >100000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients. Results: Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10000 = 53.7%; 10001-100000 = 30.0%; and >100000 = 30.8%). At viraemia <= 500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL. Conclusions: Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.File | Dimensione | Formato | |
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