HIV disease can lead to accelerated telomere attrition, although certain drugs used as part of antiretroviral therapy (ART) can inhibit telomerase reverse transcriptase activity. This could in turn lead to shorter telomeres. We hypothesized that HIV and ART exposure would be associated with shorter leukocyte telomere length (TL) in exposed mother/infant pairs compared with controls.
In these retrospective and prospective observational cohort studies, TL was evaluated in peripheral blood leukocytes obtained from HIV-infected pregnant women treated with ART and their uninfected infants, and compared with HIV untreated (retrospective cohort) or HIV mothers and their infants (prospective cohort).
In HIV-infected ART-exposed mothers, leukocyte TL was not significantly shorter than that in HIV untreated mothers or HIV controls, nor was their infants' TL significantly different. Cord blood of ART-exposed infants exhibited TL shorter than that from infants born to HIV-negative mothers. Placenta also showed evidence of shorter TL after adjustment for relevant covariates. Factors associated with shorter maternal and infant TL included smoking and the use of drugs of addiction in pregnancy.
These results suggest that maternal HIV infection or exposure to ART has minimal effect on infant leukocyte TL, a reassuring finding. In contrast, tissues that express higher telomerase activity such as umbilical cord blood and placenta appear comparatively more affected by ART. Smoking and the use of drugs of addiction have a negative impact on maternal and infant leukocyte TL, possibly through oxidative telomere damage.
[Show abstract][Hide abstract] ABSTRACT: Measurement of telomere length is crucial for the study of telomere maintenance and its role in molecular pathophysiology of diseases and in aging. Several methods are used to measure telomere length, the choice of which usually depends on the type and size of sample to be assayed, as well as cost and throughput considerations. The goal of this study was to investigate the factors that may influence the reliability of qPCR-based relative telomere length measurements in whole blood. Day to day intra-individual variability, types of blood anticoagulant, sample storage conditions, processing and site of blood draw were investigated. Two qPCR-based methods to measure telomere length (monoplex vs. multiplex) were also investigated and showed a strong correlation between them. Freezing and thawing of the blood and storage of the blood at 4°C for up to 4 days did not affect telomere length values. Telomere lengths in dried blood spots were significantly higher than both whole blood and peripheral mononuclear blood cells, and were highly correlated with both. We found that telomere length measurements were significantly higher in dried blood spots collected directly from fingertip prick compared to dried blood spots prepared with anticoagulated whole blood collected from the finger, and non-blotted whole blood taken from both finger and arm venipuncture. This suggests that DNA from cells blotted on paper is not equivalent to that collected from venipuncture whole blood, and caution should be taken when comparing between blood sample types.
PLoS ONE 02/2013; 8(2):e57787. DOI:10.1371/journal.pone.0057787 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Telomeres are protective chromosomal structures that play a key role in preserving genomic stability. Telomere length is known to be associated with ageing and age-related diseases. To study the impairment of telomeres induced by drug abuse, we conducted an association study in the Chinese Han population. Multivariate linear regression analyses were performed to evaluate the correlation of leukocyte telomere length (LTL) with addiction control status adjusted for age and gender. The results showed that drug abusers exhibited significantly shorter LTLs than controls (P = 1.32e-06). The time before relapse also presented an inverse correlation with LTL (P = 0.02). Drug abusers who had used heroin and diazepam displayed a shorter LTL than those taking other drugs (P = 0.018 and P = 0.009, respectively). Drug abusers who had ingested drugs via snuff exhibited longer LTLs than those using other methods (P = 0.02). These observations may offer a partial explanation for the effects of drug addiction on health.
[Show abstract][Hide abstract] ABSTRACT: Background:
HIV-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesised that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated ageing in HIV-infected individuals on cART via inhibition of telomerase activity.
Telomerase activity and telomere length (TL) were measured by quantitative PCR in vitro in activated peripheral blood mononuclear cells (PBMC) cultured with NRTI, and ex vivo in PBMC from uninfected patients exposed to NRTI and from HIV-infected patients on NRTI-containing cART.
Lamivudine, abacavir, zidovudine, emtricitabine and tenofovir significantly inhibited telomerase activity in activated PBMC in vitro. Tenofovir was the most potent inhibitor of telomerase activity and caused greatest shortening of TL in vitro at the therapeutic concentration of 0.3μM. PBMC from HIV-infected patients receiving NRTI-containing cART (n=39) had significantly lower telomerase activity than HIV-uninfected patients (n=47; p=0.011) and HIV-infected patients receiving non-NRTI-containing cART (n=11; p<0.001). TL was significantly inversely associated with age (p=0.009) and the total duration on any NRTI (p=0.01).
NRTIs, and specifically tenofovir at therapeutic concentrations, inhibit telomerase activity leading to accelerated shortening of TL in activated PBMC. The relationship between NRTI, reduced telomerase activity and accelerated ageing requires further investigation in HIV-infected individuals on cART.
The Journal of Infectious Diseases 04/2013; 207(7):1157. DOI:10.1093/infdis/jit006 · 6.00 Impact Factor
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