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No difference in the rate of change in telomere length or telomerase activity in HIV-infected patients after three years of darunavir/ritonavir with and without nucleoside analogues in the MONET trial.

Solomon A, Tennakoon S, Leeansyah E, Arribas J, Hill A, Van Delft Y, Moecklinghoff C, Lewin SR - PLoS ONE (2014)

Bottom Line: As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026).There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Monash University and Alfred Health, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.

ABSTRACT

Objective: To determine whether nucleos(t)ide reverse transcriptase inhibitors (NRTI) contribute to an accelerated loss in telomere length (TL) in HIV-infected patients on antiretroviral therapy (ART).

Design: Substudy of randomised controlled trial.

Methods: Patients with HIV RNA <50 copies/mL on combination ART (n = 256) were randomised to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 127) or with 2 NRTIs (n = 129) for up to 144 weeks. TL and telomerase activity was quantified on stored peripheral blood mononuclear cells (PBMC; n = 124) using quantitative real time PCR.

Results: Patients in the sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4 years (range 1-20 years). As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no significant association between TL and either the duration of prior NRTI treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).

Conclusion: Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.

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MONET trial- Telomere sub-study patient disposition.
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pone-0109718-g001: MONET trial- Telomere sub-study patient disposition.

Mentions: The sub-study to measure TL and telomerase activity was conducted on stored samples after the trial had been completed. We measured TL and telomerase activity in PBMCs from 130 of the 256 randomised patients who had stored samples available. Six of the patients in the DRV/r monotherapy arm received NRTI during the study and were therefore excluded from the eligible population (nā€Š=ā€Š124) (Figure 1).


No difference in the rate of change in telomere length or telomerase activity in HIV-infected patients after three years of darunavir/ritonavir with and without nucleoside analogues in the MONET trial.

Solomon A, Tennakoon S, Leeansyah E, Arribas J, Hill A, Van Delft Y, Moecklinghoff C, Lewin SR - PLoS ONE (2014)

MONET trial- Telomere sub-study patient disposition.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219673&req=5

pone-0109718-g001: MONET trial- Telomere sub-study patient disposition.
Mentions: The sub-study to measure TL and telomerase activity was conducted on stored samples after the trial had been completed. We measured TL and telomerase activity in PBMCs from 130 of the 256 randomised patients who had stored samples available. Six of the patients in the DRV/r monotherapy arm received NRTI during the study and were therefore excluded from the eligible population (nā€Š=ā€Š124) (Figure 1).

Bottom Line: As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026).There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Monash University and Alfred Health, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.

ABSTRACT

Objective: To determine whether nucleos(t)ide reverse transcriptase inhibitors (NRTI) contribute to an accelerated loss in telomere length (TL) in HIV-infected patients on antiretroviral therapy (ART).

Design: Substudy of randomised controlled trial.

Methods: Patients with HIV RNA <50 copies/mL on combination ART (n = 256) were randomised to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 127) or with 2 NRTIs (n = 129) for up to 144 weeks. TL and telomerase activity was quantified on stored peripheral blood mononuclear cells (PBMC; n = 124) using quantitative real time PCR.

Results: Patients in the sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4 years (range 1-20 years). As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no significant association between TL and either the duration of prior NRTI treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).

Conclusion: Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.

Show MeSH