 |
|
|
| |
Telomere length: neurocognitive biomarker in HIV-1-infected subjects
|
| |
| |
Reported by Jules Levin
CROI 2017 Feb 14-16 Seattle, WA
Marilia L. Araujo1,2 , Maria Rita. P Gascon3 , Augusto Cesar P. Oliveira3, Luiz A. Fonseca4, Raquel Paiva5 , Barbara Santana5, Rodrigo Calado5 , WellingtonDuarte1,2, Jorge Casseb1,2
1Laboratory of Dermatology andImmunodeficiencies, Dermatology Division, Clinics Hospital, Sao Paulo, Brazil; 2Institute of Tropical Medicine, University of Sao Paulo, Brazil; 3Institute of Infectious Diseases EmilioRibas, Sao Paulo, Brazil; 4Department of Preventive Medicine, University of Sao Paulo MedicalSchool,Brazil;5Laboratory of Hematology, University Hospital ofRibeiraoPreto, Sao Paulo, SP, Brazil
--------------------------------
"The relationship between NRTI, reduced telomerase activity, and accelerated aging requires further investigation in HIV-infected individuals on cART.....Another potential cause of accelerated or accentuated aging in HIV-infected patientscould be telomere shortening caused by antiretroviral drugs"
Inhibition of Telomerase Activity by Human Immunodeficiency Virus (HIV) Nucleos(t)ide Reverse Transcriptase Inhibitors: A Potential Factor Contributing to HIV-Associated Accelerated Aging - (01/20/17)
In summary, we have demonstrated that all NRTIs inhibit telomerase activity and TL in activated PBMC in vitro, with the greatest effect observed with TDF. Reduced telomerase activity was greatest in HIV-infected patients on NRTI-containing cART. An important future clinical question will be to determine whether any inhibition of telomerase by NRTIs in vivo is reversible following cessation of NRTI. The long-term effects in HIV-infected patients of NRTI exposure on telomerase activity, TL, and accelerated aging warrant further investigation."
Brief Report: Differential Effects of Tenofovir, Abacavir, Emtricitabine, and Darunavir on Telomerase Activity In Vitro- (12/09/16)
There is growing concern about the issue of aging of HIV-infected patients. It is well established that HIV-infected patients have an increased risk for several "non-AIDS" complications (cardiovascular disease, malignancy, liver disease, kidney disease, bone disease, and neurocognitive decline)that are classically associated with the normal aging process......It is also unknown if this accentuated or accelerated aging [from Jules: its accelerated in general, not accentuated depending on the specific comorbidity] is caused by theproinflammatory state associated with even well-controlled HIV infection, traditional risk factors (such as smoking) that are more prevalent among HIV-infected people, or other still unknown causes.......Another potential cause of accelerated or accentuated aging in HIV-infected patientscould be telomere shortening caused by antiretroviral drugs.5There is a close association between shortened telomere length (TL) in peripheral blood mononuclear cells (PBMCs) and diseases of aging, including increased cardiovascular diseases and dementia.6,7
"In our study, we explored if N(t)RTIs could play a role in the aging process of HIV-infected patients by means of inhibition of telomerase activity and whether DRV could have a similar effect. We have found that TFV and ABC, but not FTC, produced a significant dose-dependent decrease of telomerase activity in PHA-activated PBMCs within the therapeutic concentration range in vivo. After 72 hours of treatment, telomerase inhibition caused by TFV was more than double the inhibition caused by ABC: 29% and 12%, respectively. The observed decrease in telomerase activity caused by TFV and ABC was not associated with a decrease in hTERT protein level, or a change in the expression ofhTERTgene or the other genes that code for the subunits of the telomerase/shelterin complexes. Furthermore, we have shown that DRV did not affect telomerase activity,hTERTgene expression, or hTERT protein levels."
---------------------------------
|
| |
|
|
|
|
|
