Impact of Antiretroviral Treatment Containing Tenofovir Difumarate on the Telomere Length of Aviremic HIV-Infected Patients

Abstract

Our data do not suggest that telomerase activity inhibition caused by TDF in vitro leads to telomere shortening in peripheral blood of HIV-infected patients.

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

“…Regarding antiretroviral therapy, there is a lot of similarity in function between HIV reverse transcriptase and telomerase, which results in telomerase being putatively blocked by NRTIs [5,17,18]. In vivo trials have indicated that TDF is the only NRTI that significantly inhibits telomerase activity and reduces telomere size at therapeutic concentrations [5], although these findings were not confirmed by other studies [19,20]. In this setting, our study is consistent with previous results, according to which TDF treatment had no effect on RTL.…”

ATM Deficiency Accelerates DNA Damage, Telomere Erosion, and Premature T Cell Aging in HIV-Infected Individuals on Antiretroviral Therapy

“…Specifically, HIV latency in the era of cART is characterized by the existence of viral reservoirs that prevent HIV-1 eradication and likely drive inflammaging (46, 47). Thus, HIV-mediated inflammaging could result from a myriad of insults, such as viral particles or viral RNAs/proteins released from the reservoirs, cell-secreted pro-inflammatory cytokines, HIV-enhanced gut permeability and altered gut microbiota or dysbiosis, frequent cytomegalovirus (CMV), Epstein–Barr virus (EBV), hepatitis B virus (HBV), and HCV coinfections, the cART regimen itself (NRTIs may take part in telomere damage and T cell senescence, as telomerase has been shown to be inhibited by some NRTIs) (48), as well as other comorbidities including malignancies, personal stresses, or social and environmental factors (49–52). In addition to central memory CD4 T cells, several groups have reported that T stem cell memory (T SCM ) cells harbor HIV-1 provirus and are relatively “spared” from depletion as compared to other CD4 T cells (53, 54).…”

Determinants of blood telomere length in antiretroviral treatment‐naïve HIV‐positive participants enrolled in the NEAT 001/ANRS 143 clinical trial

“…Genomic DNA was isolated from whole blood using the QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Relative telomere length, expressed as the ratio of telomere (T) to single‐copy gene (S), was determined by monochrome quantitative multiplex PCR assay with minor modifications as described in our previous study . A standard curve was prepared with genomic DNA from a pool of three healthy volunteers by serial dilution and was included in triplicate in each run together with a reference sample and negative control.…”

“…Although it is well known that HIV-infected persons have a shorter blood TL than the general population, to the best of our knowledge there are no studies evaluating factors associated with TL during untreated chronic HIV infection. The majority of previous studies have evaluated determinants of TL shortening in persons living with HIV who are already receiving ART [9][10][11][12][13][14]. The few studies evaluating TL in untreated HIV infection were very limited in sample size, with a maximum of 73 participants [15][16][17].…”