PMID- 23303810
OWN - NLM
STAT- MEDLINE
DCOM- 20130418
LR  - 20151119
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 207
IP  - 7
DP  - 2013 Apr
TI  - Inhibition of telomerase activity by human immunodeficiency virus (HIV) 
      nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing 
      to HIV-associated accelerated aging.
PG  - 1157-65
LID - 10.1093/infdis/jit006 [doi]
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients on combination 
      active antiretroviral therapy (cART) are at increased risk of age-related 
      complications. We hypothesized that nucleos(t)ide reverse transcriptase 
      inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals 
      on cART via inhibition of telomerase activity. METHODS: Telomerase activity and 
      telomere length (TL) were measured by quantitative polymerase chain reaction in 
      vitro in activated peripheral blood mononuclear cells (PBMCs) cultured with NRTI 
      and ex vivo in PBMCs from uninfected patients exposed to NRTI and from 
      HIV-infected patients on NRTI-containing cART. RESULTS: Lamivudine, abacavir, 
      zidovudine, emtricitabine, and tenofovir significantly inhibited telomerase 
      activity in activated PBMCs in vitro. Tenofovir was the most potent inhibitor of 
      telomerase activity and caused greatest shortening of TL in vitro at the 
      therapeutic concentration of 0.3 muM. PBMCs from HIV-infected patients receiving 
      NRTI-containing cART (n = 39) had significantly lower telomerase activity than 
      HIV-uninfected patients (n = 47; P = .011) and HIV-infected patients receiving 
      non-NRTI-containing cART (n = 11; P < .001). TL was significantly inversely 
      associated with age (P = .009) and the total duration on any NRTI (P = .01). 
      CONCLUSIONS: NRTIs and, specifically tenofovir at therapeutic concentrations, 
      inhibit telomerase activity leading to accelerated shortening of TL in activated 
      PBMCs. The relationship between NRTI, reduced telomerase activity, and 
      accelerated aging requires further investigation in HIV-infected individuals on 
      cART.
FAU - Leeansyah, Edwin
AU  - Leeansyah E
AD  - Department of Medicine, Monash University, Melbourne, Australia.
FAU - Cameron, Paul U
AU  - Cameron PU
FAU - Solomon, Ajantha
AU  - Solomon A
FAU - Tennakoon, Surekha
AU  - Tennakoon S
FAU - Velayudham, Pushparaj
AU  - Velayudham P
FAU - Gouillou, Maelenn
AU  - Gouillou M
FAU - Spelman, Tim
AU  - Spelman T
FAU - Hearps, Anna
AU  - Hearps A
FAU - Fairley, Christopher
AU  - Fairley C
FAU - Smit, De Villiers
AU  - Smit de V
FAU - Pierce, Anna B
AU  - Pierce AB
FAU - Armishaw, Jude
AU  - Armishaw J
FAU - Crowe, Suzanne M
AU  - Crowe SM
FAU - Cooper, David A
AU  - Cooper DA
FAU - Koelsch, Kersten K
AU  - Koelsch KK
FAU - Liu, Jun-Ping
AU  - Liu JP
FAU - Chuah, John
AU  - Chuah J
FAU - Lewin, Sharon R
AU  - Lewin SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130109
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (Organophosphonates)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 2T8Q726O95 (Lamivudine)
RN  - 4B9XT59T7S (Zidovudine)
RN  - 99YXE507IL (Tenofovir)
RN  - EC 2.7.7.49 (Telomerase)
RN  - G70B4ETF4S (Emtricitabine)
RN  - JAC85A2161 (Adenine)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Adenine/adverse effects/*analogs & derivatives
MH  - Adult
MH  - Aging/*drug effects
MH  - Anti-HIV Agents/*adverse effects
MH  - Antiretroviral Therapy, Highly Active/adverse effects
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Deoxycytidine/adverse effects/analogs & derivatives
MH  - Dideoxynucleosides/adverse effects
MH  - Emtricitabine
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - HIV/pathogenicity
MH  - HIV Infections/*drug therapy/pathology/virology
MH  - Humans
MH  - Lamivudine/adverse effects
MH  - Leukocytes, Mononuclear/drug effects/enzymology
MH  - Male
MH  - Middle Aged
MH  - Organophosphonates/*adverse effects
MH  - Polymerase Chain Reaction
MH  - Regression Analysis
MH  - Reverse Transcriptase Inhibitors/*adverse effects
MH  - Risk Factors
MH  - Telomerase/*antagonists & inhibitors/metabolism
MH  - Telomere/drug effects/enzymology
MH  - Telomere Shortening
MH  - Tenofovir
MH  - Time Factors
MH  - Young Adult
MH  - Zidovudine/adverse effects
EDAT- 2013/01/11 06:00
MHDA- 2013/04/20 06:00
CRDT- 2013/01/11 06:00
PHST- 2013/01/11 06:00 [entrez]
PHST- 2013/01/11 06:00 [pubmed]
PHST- 2013/04/20 06:00 [medline]
AID - jit006 [pii]
AID - 10.1093/infdis/jit006 [doi]
PST - ppublish
SO  - J Infect Dis. 2013 Apr;207(7):1157-65. doi: 10.1093/infdis/jit006. Epub 2013 Jan 
      9.