Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

TitleDetection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study
Publication TypeJournal Article
Year of Publication2011
AuthorsProsperi M.C, Mackie N, Di Giambenedetto S., Zazzi M, Camacho R., Fanti I., Torti C., Sonnerborg A., Kaiser R., Codoner F.M, Van Laethem K., Bansi L, van de Vijver D.A, Geretti AM, De Luca A.
JournalJ Antimicrob Chemother
Volume66
Pagination1886-96
Date PublishedAug
ISBN Number0305-7453
Accession Number21624929
Keywords*Drug Resistance, Viral, *Mutation, Missense, *Viral Load, Adult, Anti-HIV Agents/administration & dosage, CD4 Lymphocyte Count, Cohort Studies, Europe, Female, Genotype, HIV Infections/drug therapy/*virology, HIV-1/*drug effects/isolation & purification, Humans, Male, RNA, Viral/*genetics/isolation & purification, Viral Proteins/*genetics
Abstract

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 16 511 HIV-1 reverse transcriptase and protease sequences from 11 492 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.

Short TitleThe Journal of antimicrobial chemotherapy
Alternate JournalThe Journal of antimicrobial chemotherapy