Trans-Activation Response Element RNA is Detectable in the Plasma of a Subset of Aviremic HIV-1-Infected Patients.

Anžej Hladnik,Ana Plemenitaš,Boris M Peterlin,Vita Dolžan,Katja Goričar,Metka Lenassi,Jana Ferdin,Steven G Deeks

doi:10.17344/acsi.2016.2863

Anžej Hladnik, Ana Plemenitaš + Show 6 more

Open Access

https://doi.org/10.17344/acsi.2016.2863

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Abstract

Determining the HIV-1 reservoir size in infected individuals is of great importance for improvement of their treatment. Plasma trans-activation response element (TAR) RNA has been suggested as one of the possible biomarkers. TAR RNA is produced during non-processive transcription in HIV-1 productively infected and latent T cells. Here, plasma samples and paired exosome samples of 55 subjects from the observational SCOPE cohort were analysed for the presence of TAR RNA. First, a PCR-based assay was optimized, which provided 100% specificity and 100% sensitivity in differentiating HIV-1 infected non-controllers from uninfected individuals. Next, TAR RNA was detected in the plasma of 63% of aviremic HIV-1-infected patients, who were either treated with antiretroviral therapy or were elite controllers. Although TAR RNA levels did not correlate with patient gender, age, CD4 levels, CD8 levels, they tended to correlate with CD4/CD8 ratio (P = 0.047). This study is the first to investigate plasma TAR RNA in a relatively large cohort of HIV-1-infected patients. We additionally show that the TAR RNA molecules in the plasma of aviremic patients are not limited to exosomes.

Highlights

HIV remains a major global public health issue, and the World Health Organisation has estimated that around 36.7 million people were infected at the end of 2015
Determination of the HIV-1 reservoir size in infected individuals is of great importance for the improvement of their treatment, and plasma trans-activation response element (TAR) RNA might serve as one such biomarker
TAR RNA was previously detected in two sera and sera-exosome-enriched samples from aviremic antiretroviral therapy (ART)-suppressed patients and elite controllers,[16] and in an additional four sera exosome-enriched samples from aviremic ART-suppressed patients.[17]

Summary

Introduction

HIV remains a major global public health issue, and the World Health Organisation has estimated that around 36.7 million people were infected at the end of 2015. In the majority of HIV-1–infected patients, the combination antiretroviral therapy (ART) reduces plasma HIV-1 RNA to clinically undetectable levels. This treatment cannot eradicate proviruses hidden in CD4 T cells and other latent reservoirs.[1] Over 90% of these proviruses are believed to be defective, such that they cannot produce intact viruses,[2] they were recently shown to produce novel protein-encoding RNA species.[3] These might contribute to chronic inflammation, which together with antiretroviral drug toxicity and the traditional risk factors, might promote increased risk of developing non-. AIDS–associated diseases in ART-treated adults (e.g., cardiovascular, liver, renal and bone diseases, cancers).[4,5,6] determination of the size of the HIV-1 reservoir in aviremic individuals is important for the understanding of HIV pathogenesis and to adjust the therapy to improve the quality of life of the patient

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