Use of cellular HIV DNA to predict virologic response to maraviroc: performance of population-based and deep sequencing.

2013 | Clinical Infectious Disease

Program(s): Laboratory |

Abstract:

BACKGROUND:

A tropism test is required before administration of the antiretroviral drug maraviroc. However, plasma RNA testing is not possible in patients with undetectable plasma viral loads. Here we assess genotypic testing of cellular human immunodeficiency virus (HIV) DNA from peripheral blood mononuclear cells (PBMCs) to predict virologic responses in treatment-experienced patients beginning maraviroc-containing regimens.

METHODS:

PBMC samples from 181 maraviroc recipients at study entry in MOTIVATE or A4001029 (51% R5 by original Trofile). The V3 loop was amplified in triplicate from cellular HIV DNA, and matching plasma RNA (n = 156). Sequencing was performed using standard population-basedmethods and next-generation deep sequencing, with tropism assessment as previously defined.

RESULTS:

Genotypic DNA-based tropism testing from the cellular compartment had 78%-81% sensitivity relative to RNA-based Trofile at the same time point. Cell-based genotypic tropism methods and plasma-based phenotypic and genotypic methods were predictive of virologic response. However, when classifications were discordant, the outcomes favored the plasma predictions over the DNA ones.

CONCLUSIONS:

Genotypic determination of HIV tropism can be performed using cell-derived viral DNA, and is a predictor of virologic success onmaraviroc in therapy-experienced patients. However, the PBMC compartment appears to be a suboptimal predictor compared to plasma.

Text or Node

Swenson L

BC Centre for Excellence in HIV/AIDS

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Use of cellular HIV DNA to predict virologic response to maraviroc: performance of population-based and deep sequencing.

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