Rapid Decrease in Peripheral Blood Mononucleated Cell Telomere Length After HIV Seroconversion, but Not HCV Seroconversion

González‐Serna, Alejandro; Ajaykumar, Abhinav; Gadawski, Izabelle; Muñoz‐Fernández, María Ángeles; Hayashi, Kanna; Harrigan, P. Richard; Côté, Hélène

doi:10.1097/qai.0000000000001446

Cited by 22 publications

(12 citation statements)

References 19 publications

(23 reference statements)

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“…In our study, HIV infection had a great impact on telomere length, because HIV/HCV-coinfected patients had lower RTL values in PBMCs than HCV-monoinfected patients, both at baseline and at 48 weeks after DAA therapy, regardless of other clinical and epidemiological factors. HIV triggers a reduction of telomere length [3,4], which may be mitigated by ART [1]. However, this putative protective effect is not enough to compensate for the HIV reduction of telomere length, as RTL values are lower in HIV patients on ART than in healthy controls [16].…”

Section: Discussionmentioning

confidence: 99%

“…HIV promotes chronic immune activation, oxidative stress, inflammation, and an accelerating loss of telomere length in immune cells during the acute and chronic phase of infection [2]. Telomere reduction seems to occur from the first point of HIV infection, and may be maintained during HIV infection without antiretroviral therapy (ART) [3,4]. There is evidence that ART and control of HIV viremia have beneficial effects on telomere length [1].…”

Section: Introductionmentioning

confidence: 99%

“…Chronic hepatitis C (CHC) leads to a decrease in telomere length of T-cells, which seems to be more related to the severity of liver disease than to the HCV infection itself [4,6,7]. In the liver, hepatocyte telomeres are shorter in cirrhotic patients [8].…”

Section: Introductionmentioning

confidence: 99%

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

Molina-Carrión

Brochado-Kith

González-García

et al. 2020

JCM

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Introduction: Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Methods: Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child–Pugh–Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. Results: In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). Conclusion: HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Molina-Carrión

Brochado-Kith

González-García

et al. 2020

JCM

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“…Blood TL substantially shortens early after HIV seroconversion. In one study of 51 injecting drug users [2], blood TL had decreased by 13% 3 months after HIV seroconversion. In another study of 31 injecting drug users [3], blood TL decreased at a rate of approximately 650 base pairs/year during the first 2 years following HIV seroconversion.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Objectives Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open‐label trial comparing ritonavir‐boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)‐naïve HIV‐positive adults. Methods A cross‐sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. Results The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV‐1 RNA load was 4.7 log10 HIV‐1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/μL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV‐1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/μL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. Conclusions Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.

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“…Notably, most data on TL in HIV-positive persons is limited by a cross-sectional design and the absence of appropriate controls; however, it tends to suggest shorter TL in HIV-positive persons compared to HIV-negative controls [15, 16]. Preliminary data on patients with pre- and post-HIV seroconversion measurements suggests that significant TL shortening occurs in the setting of HIV seroconversion [17]. However, there is no solid data suggesting that, after seroconversion, HIV-positive persons have accelerated TL shortening over time compared to HIV-negative persons.…”

Section: Have Studies On Telomere Length Improved Our Understanding Omentioning

confidence: 99%

HIV and Aging – Perhaps Not as Dramatic as We Feared?

et al. 2018

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Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to “metabolic” complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims of this viewpoint paper are to summarize recent data and to examine the possibility that the problem of aging-related morbidity in HIV might not be as dramatic as previously believed.

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Rapid Decrease in Peripheral Blood Mononucleated Cell Telomere Length After HIV Seroconversion, but Not HCV Seroconversion

Cited by 22 publications

References 19 publications

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

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

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

HIV and Aging – Perhaps Not as Dramatic as We Feared?

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