TY - JOUR
T1 - Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study
AU - Mancuso, Salvatrice
AU - Bansi, Loveleen
AU - Fanti, Iuri
AU - Prosperi, Mattia C.F.
AU - Van Laethem, Kristel
AU - Kaiser, Rolf
AU - Van De Vijver, David A.M.C.
AU - Camacho, Ricardo
AU - Di Giambenedetto, Simona
AU - Geretti, Anna Maria
AU - Mackie, Nicola
AU - Torti, Carlo
AU - Zazzi, Maurizio
AU - Sönnerborg, Anders
AU - De Luca, Andrea
AU - Codoñer, Francisco M.
AU - Camacho, Ricardo
PY - 2011
Y1 - 2011
N2 - Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. Methods: A total of 16511 HIV-1 reverse transcriptase and protease sequences from 11492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs. Results: Overall, 2500/16 511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL. Conclusions: Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
AB - Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. Methods: A total of 16511 HIV-1 reverse transcriptase and protease sequences from 11492 treatment-experienced patients were identified, and linked to clinical data on viral load, CD4 T cell counts and antiretroviral treatment history. Test results from 3162 treatment-naive patients served as controls. Multivariable analysis was employed to identify predictors of reverse transcriptase and protease DRMs. Results: Overall, 2500/16 511 (15.14%) test results were obtained at a viral load <1000 copies/mL. Individuals with viral load levels of 1000-10000 copies/mL showed the highest probability of drug resistance to any drug class. Independently from other measurable confounders, treatment-experienced patients showed a trend for DRMs and other mutations to decrease at viral load levels <500 copies/mL. Conclusions: Genotypic testing at low viral load may identify emerging antiretroviral drug resistance at an early stage, and thus might be successfully employed in guiding prompt management strategies that may reduce the accumulation of resistance and cross-resistance, viral adaptive changes, and larger viral load increases. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
KW - Genotypic testing; HIV; Viral load; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Europe; Female; Genotype; HIV Infections; HIV-1; Humans; Male; RNA
KW - Missense; Viral Load; Pharmacology; Pharmacology (medical); Infectious Diseases
KW - Viral; Mutation
KW - Viral; Viral Proteins; Drug Resistance
KW - Genotypic testing; HIV; Viral load; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Cohort Studies; Europe; Female; Genotype; HIV Infections; HIV-1; Humans; Male; RNA
KW - Missense; Viral Load; Pharmacology; Pharmacology (medical); Infectious Diseases
KW - Viral; Mutation
KW - Viral; Viral Proteins; Drug Resistance
UR - http://hdl.handle.net/10447/215395
M3 - Article
VL - 66
SP - 1886
EP - 1896
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
ER -