BACKGROUND: We evaluated reliability and clinical usefulness of genotypic resistance testing (GRT) in patients for whom combination antiretroviral therapy (cART) was unsuccessful with viremia levels 50-1000 copies/mL, for whom GRT is generally not recommended by current guidelines. METHODS: The genotyping success rate was evaluated in 12 828 human immunodeficiency virus type 1 (HIV-1) plasma samples with viremia >50 copies/mL, tested using the commercial ViroSeq HIV-1 Genotyping System or a homemade system. Phylogenetic analysis was performed to test the reliability and reproducibility of the GRT at low-level viremia (LLV). Drug resistance was evaluated in 3895 samples from 2200 patients for whom treatment was unsuccessful (viremia >50 copies/mL) by considering the resistance mutations paneled in the 2013 International Antiviral Society list. RESULTS: Overall, the success rate of amplification/sequencing was 96.4%. Viremia levels of 50-200 and 201-500 copies/mL afforded success rates of 67.2% and 88.1%, respectively, reaching 93.2% at 501-1000 copies/mL and ≥97.3% above 1000 copies/mL. A high homology among sequences belonging to the same subject for 96.4% of patients analyzed was found. The overall resistance prevalence was 74%. Drug resistance was commonly found also at LLV. In particular, by stratifying for different viremia ranges, detection of resistance was as follows: 50-200 copies/mL = 52.8%; 201-500 = 70%; 501-1000 = 74%; 1001-10 000 = 86.1%; 10 001-100 000 = 76.7%; and >100 000 = 63% (P < .001). Similar bell-shaped results were found when the GRT analysis was restricted to 2008-2012, although at a slightly lower prevalence. CONCLUSIONS: In patients failing cART with LLV, HIV-1 genotyping provides reliable and reproducible results that are informative about emerging drug resistance

Santoro, M., Fabeni, L., Armenia, D., Alteri, C., Di Pinto, D., Forbici, F., et al. (2014). Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels. CLINICAL INFECTIOUS DISEASES, 58(8), 1156-1164 [10.1093/cid/ciu020].

Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels

SANTORO, MARIA;BERTOLI, ADA;ANDREONI, MASSIMO;CECCHERINI SILBERSTEIN, FRANCESCA;PERNO, CARLO FEDERICO
2014-04

Abstract

BACKGROUND: We evaluated reliability and clinical usefulness of genotypic resistance testing (GRT) in patients for whom combination antiretroviral therapy (cART) was unsuccessful with viremia levels 50-1000 copies/mL, for whom GRT is generally not recommended by current guidelines. METHODS: The genotyping success rate was evaluated in 12 828 human immunodeficiency virus type 1 (HIV-1) plasma samples with viremia >50 copies/mL, tested using the commercial ViroSeq HIV-1 Genotyping System or a homemade system. Phylogenetic analysis was performed to test the reliability and reproducibility of the GRT at low-level viremia (LLV). Drug resistance was evaluated in 3895 samples from 2200 patients for whom treatment was unsuccessful (viremia >50 copies/mL) by considering the resistance mutations paneled in the 2013 International Antiviral Society list. RESULTS: Overall, the success rate of amplification/sequencing was 96.4%. Viremia levels of 50-200 and 201-500 copies/mL afforded success rates of 67.2% and 88.1%, respectively, reaching 93.2% at 501-1000 copies/mL and ≥97.3% above 1000 copies/mL. A high homology among sequences belonging to the same subject for 96.4% of patients analyzed was found. The overall resistance prevalence was 74%. Drug resistance was commonly found also at LLV. In particular, by stratifying for different viremia ranges, detection of resistance was as follows: 50-200 copies/mL = 52.8%; 201-500 = 70%; 501-1000 = 74%; 1001-10 000 = 86.1%; 10 001-100 000 = 76.7%; and >100 000 = 63% (P < .001). Similar bell-shaped results were found when the GRT analysis was restricted to 2008-2012, although at a slightly lower prevalence. CONCLUSIONS: In patients failing cART with LLV, HIV-1 genotyping provides reliable and reproducible results that are informative about emerging drug resistance
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - Microbiologia e Microbiologia Clinica
English
Con Impact Factor ISI
HIV-1 low viremia; phylogenesis; drug resistance; HIV-1 genotyping; clinical outcome
Santoro, M., Fabeni, L., Armenia, D., Alteri, C., Di Pinto, D., Forbici, F., et al. (2014). Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels. CLINICAL INFECTIOUS DISEASES, 58(8), 1156-1164 [10.1093/cid/ciu020].
Santoro, M; Fabeni, L; Armenia, D; Alteri, C; Di Pinto, D; Forbici, F; Bertoli, A; Di Carlo, D; Gori, C; Carta, S; Fedele, V; D'Arrigo, R; Berno, G; Ammassari, A; Pinnetti, C; Nicastri, E; Latini, A; Tommasi, C; Boumis, E; Petrosillo, N; D'Offizi, G; Andreoni, M; CECCHERINI SILBERSTEIN, F; Antinori, A; Perno, Cf
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/89703
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