Inhibition of Telomerase Activity by Human Immunodeficiency Virus (HIV) Nucleos(t)ide Reverse Transcriptase Inhibitors: A Potential Factor Contributing to HIV-Associated Accelerated Aging

Leeansyah, Edwin; Cameron, Paul; Solomon, Ajantha; Tennakoon, Surekha; Velayudham, Pushparaj; Gouillou, Maëlenn; Spelman, Tim; Hearps, Anna C.; Fairley, Christopher K.; Smit, De Villiers; Pierce, Anna; Armishaw, Jude; Crowe, Suzanne; Cooper, David A.; Koelsch, Kersten K.; Liu, Junping; Chuah, John; Lewin, Sharon R.

doi:10.1093/infdis/jit006

Cited by 115 publications

(93 citation statements)

References 47 publications

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“…In the early times of HIV epidemic, NRTIs, including azidothymidine (AZT), didanosine (ddI), and abacavir (ABC) [156-160] were proven to be able to reduce telomerase activity and TL in vitro. More recently, tenofovir (TDF), lamivudine (3TC), and emtricitabine (FTC) have also been found to diminish telomerase activity and TL in vitro [161]. Given the key role of telomerase in the ageing process [162], it has been hypothesized that telomerase inhibition, and possibly NRTI-associated mitochondrial damage, could participate in the premature ageing observed in ART-treated patients.…”

Section: Effect Of Art On Telomerase Activity Of T Cellsmentioning

confidence: 99%

“…In the study by Leeansyah et al [165], TL and telomerase activity was analysed in total PBMCs, because the authors hypothesized that if NRTI inhibits telomerase activity, this should occur not only in CD4+ T cells, but in all peripheral blood cells expressing telomerase [161]. The authors detected a significant reduction of telomerase activity (but not of TL) in patients on NRTI-containing therapy, and suggested that the lack of significant shortening of TL in total PBMCs could be ascribed to the divergent changes in TL that have been described for CD4+ and CD8+ T cells.…”

Section: Effect Of Art On Telomerase Activity Of T Cellsmentioning

confidence: 99%

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Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Franzese¹,

Barbaccia²,

Bonmassar³

et al. 2018

Chemotherapy

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Since the introduction of highly active antiretroviral therapy more than 2 decades ago, HIV-related deaths have dramatically decreased and HIV infection has become a chronic disease. Due to the inability of antiretroviral drugs to eradicate the virus, treatment of HIV infection requires a systemic lifelong therapy. However, even when successfully treated, HIV patients still show increased incidence of age-associated co-morbidities compared with uninfected individuals. Virus- induced immunosenescence, a process characterized by a progressive decline of immune system function, contributes to the premature ageing observed in HIV patients. Although antiretroviral therapy has significantly improved both the quality and length of patient lives, the life expectancy of treated patients is still shorter compared with that of uninfected individuals. In particular, while antiretroviral therapy can contrast some features of HIV-associated immunosenescence, several anti-HIV agents may themselves contribute to other aspects of immune ageing. Moreover, older HIV patients tend to have a worse immunological response to the antiviral therapy. In this review we will examine the available evidence on the role of antiretroviral therapy in the control of the main features regulating immunosenescence.

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Section: Effect Of Art On Telomerase Activity Of T Cellsmentioning

confidence: 99%

Section: Effect Of Art On Telomerase Activity Of T Cellsmentioning

confidence: 99%

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Franzese¹,

Barbaccia²,

Bonmassar³

et al. 2018

Chemotherapy

View full text Add to dashboard Cite

show abstract

“…It is important to note that data from diverse experiments suggest alternatives to the OS theory of aging and have produced results implicating other causal factors for changes in aging processes, such as a lowering of body temperature and associated hypometabolic state, telomerase shortening and alterations in gene expression [78,79]. These factors have been associated with an increased production of prooxidants and induction of OS.…”

Section: Integrative Analysismentioning

confidence: 99%

“…TERT activity is vital to telomerase functions and because of the key role of telomerase in aging theories, it was hypothesized that this inhibition could contribute to the premature aging in HIV/AIDS, and help promote the looming epidemic of premature aging in that population [59,78].…”

Section: Integrative Analysismentioning

confidence: 99%

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

Valle¹

2014

Epidemiol

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Metabolic issues persist in HIV patients who are otherwise stable with and without antiretroviral treatment. Metabolic alterations are associated to chronic inflammation, severe mitochondrial toxicity and oxidative stress as critical factors influencing HIV disease outcomes even during antiretroviral treatment. These aspects could also be involved in comorbidities and premature aging. Both factors should be managed during therapy and they should be focus of intense ongoing investigation.The aim of this mini-review is to describe essential mechanisms of in vivo reactive oxygen species generation, antioxidants pathways, and oxidative stress involved in HIV disease. Potential impact on reactive oxygen species, oxidative damage, cellular function, and how these responses change could mediate aging in pathophysiological situations are discussed. Accrual experimental and clinical reports analyses allow us a better understanding of various inter-related contributing factors. In addition, oxidative stress as an often-overlooked link between HIVinfection and the progression of aids, during antiretroviral treatment, is analyzed. Potential long-term consequences of antioxidant treatment require on-going investigation in order to obtain important clinical issues that have recently been reported. Currently, the most practical advice is to start antiretroviral therapy early and to manage traditional risk factors of non-aids-related conditions.

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“…15,17 Moreover, telomerase activity could be also compromised by HIV-1 treatment because this enzyme shares homology with one of the main cART targets, the nucleoside reverse transcriptase. 19 In fact, nucleoside reverse transcriptase inhibitors (NRTI) have been shown to inhibit telomerase activity both in vitro and ex vivo [20][21][22] and to shorten TL. [22][23][24] Oxidative reactions are also important factors underlying the aging process.…”

Section: Introductionmentioning

confidence: 99%

Shorter Telomere Length Predicts Poorer Immunological Recovery in Virologically Suppressed HIV-1–Infected Patients Treated With Combined Antiretroviral Therapy

Blanco

Jarrín

Martı́nez

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Inhibition of Telomerase Activity by Human Immunodeficiency Virus (HIV) Nucleos(t)ide Reverse Transcriptase Inhibitors: A Potential Factor Contributing to HIV-Associated Accelerated Aging

Cited by 115 publications

References 47 publications

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

Shorter Telomere Length Predicts Poorer Immunological Recovery in Virologically Suppressed HIV-1–Infected Patients Treated With Combined Antiretroviral Therapy

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