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

Prosperi, Mattia C F, Mackie, Nicola, Di Giambenedetto, Simona, Zazzi, Maurizio, Camacho, Ricardo, Fanti, Iuri, Torti, Carlo, Sönnerborg, Anders, Kaiser, Rolf, Codoñer, Francisco M, Van Laethem, Kristel, Bansi, Loveleen, van de Vijver, David A M C, Geretti, Anna Maria, De Luca, Andrea, The SEHERE Consortium, and Fisher, Martin (2011) Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study. The Journal of antimicrobial chemotherapy, 66 (8). pp. 1886-1896. ISSN 1460-2091

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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.

Item Type: Article
Additional Information: Martin Fisher is not named author on this journal article but is a member of The SEHERE Consortium.
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Ellen Thomas
Date Deposited: 14 Feb 2014 12:27
Last Modified: 14 Feb 2014 12:27
URI: http://sro.sussex.ac.uk/id/eprint/47510
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