Correlation between blood telomere length and CD4+ CD8+ T-cell subsets changes 96 weeks after initiation of antiretroviral therapy in HIV-1-positive individuals.

Mathieu Chalouni,Rodolphe Thiebaut,Natalia Stella-Ascariz,On Behalf Of The Neat 001/Anrs 143 Trial Study Group ,Assia Samri,Hernando Knobel,Belen Alejos Ferreras,François Raffi,Javier Rodriguez-Centeno,David Zucman,Julian Blanco,Brigitte Autran,Jose Ramon Arribas,Cedrick Wallet

doi:10.1371/journal.pone.0230772

Mathieu Chalouni, Rodolphe Thiebaut + Show 12 more

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In 31 participants who started first-line antiretroviral therapy in the NEAT 001/ANRS 143 clinical trial, we found after 96 weeks a statistically significant increase in blood telomere length (TL) of 0.04 (T/S Ratio) (p = 0.03). This increase was positively correlated with both the change in the percentage of CD4+ T-cells and with the decrease of CD38+ molecules on Central Memory CD8+ and negatively correlated with the change in the percentage of CD4+ Effector Memory cells. Increase in TL could be an expression of immune reconstitution and the associated decrease in immune activation. We acknowledge for the low statistical power due to the small sample size and the potential for false positive results due to multiple testing. Hence, further studies are needed to confirm these observations.

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Untreated HIV infection causes an accelerated aging of the human immune system, an alteration known as immunosenescence
In the NEAT 001/ANRS 143 study, a randomised clinical trial that showed non-inferiority over 96 weeks of boosted darunavir/ritonavir plus raltegravir vs boosted darunavir/ritonavir (DRV/r) plus tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) in 805 antiretroviral naïve HIV-infected adults [3], we have reported a significant increase of blood telomere length (TL) after 96 weeks of follow-up, with a significant higher gain in blood TL in participants receiving boosted darunavir/ritonavir plus TDF/FTC compared to those receiving boosted darunavir/ritonavir plus raltegravir [4]
Mode of HIV transmission was significantly different between included participants and participants excluded due to inappropriate blood samples or flow cytometry was not performed were frequently

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Untreated HIV infection causes an accelerated aging of the human immune system, an alteration known as immunosenescence. HIV associated immunosenescence shares many characteristics inherent to the normal aging of the human immune system [1]: reduced thymic function, low naïve/memory cell ratio, low CD4+/CD8+ ratio, a shift of the maturation of Tcells towards phenotypes of limited proliferative potential (CD27- CD28-) with short telomeres and increased expression of the immunosenescence marker CD57. French National Institute for Health and Medical Research–France Recherche Nord and Sud SidaHIV Hepatites (Inserm-ANRS) was the sponsor and a founder of the trial. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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