Telomere length is associated with HIV infection, methamphetamine use, inflammation, and comorbid disease risk

Abstract

Background: HIV infection and methamphetamine dependence (METH) are each associated with inflammation and premature aging, but their impact on biological aging is difficult to measure. Here we examined the impact of HIV and METH on leukocyte telomere lengths (LTL), and the correlations between LTL and other aging biomarkers.

Methods: The study was a cross-sectional analysis of 161 individuals categorized by HIV and methamphetamine (METH) dependence status into four groups: HIV-METH- (n = 50), HIV-METH+ (n = 29), HIV + METH- (n = 40), and HIV + METH+ (n = 42). We analyzed the relationships of leukocyte telomere length (telomere to single copy gene [T/S] ratio) with demographic and clinical data as well as a panel of biomarkers of inflammation and endothelial activation measured in blood and cerebrospinal fluid (CSF).

Results: HIV and METH were independently associated with shorter T/S ratio, even after adjusting for demographics and leukocyte count (R² = 0·59, p < 0·0001). Higher plasma C-reactive protein (p = 0·0036) and CSF VCAM-1 (p = 0·0080) were also associated with shorter T/S ratio. A shorter T/S ratio was associated with higher risk for cardiovascular disease (p < 0·0001) and stroke (p < 0·0001), worse motor functioning (p = 0·037) and processing speed (p = 0·023), more depressive symptoms (p = 0·013), and higher CSF neurofilament-light (p = 0·003).

Conclusions: HIV and METH dependence were each associated with shorter telomeres. After adjusting for demographics, HIV, and METH, T/S ratio remained associated with aging-related outcomes including neurocognitive impairment, neurodegeneration, risks of cardiovascular disease and stroke. While not establishing causality, this study supports using the T/S ratio as a biomarker for estimating the impact of HIV and comorbidities on long-term health.

Keywords: Aging; Cardiovascular; HIV; Methamphetamine; Telomeres.

Figure 1.. Chronological and Estimated Biological Age by Group.

The chronological age of METH users in the cohort is younger than the HIV−METH− group but their biological age is older in fully adjusted models, indicating an adverse effect of METH on biological aging. HIV was independently associated with older estimated biological age. a) Difference between the chronological age of members of the three risk groups and the mean age of the HIV−METH− group. b) Estimated biological age relative to the HIV−METH− group adjusted for demographic covariates (chronological age, sex, race/ethnicity, education) and leukocyte count. c) Estimated biological age relative to the HIV−METH− group fully adjusted for all covariates in the best multivariable model (adds BMI, Globulins, and Creatinine to the prior model).

Figure 2.. Correlation of Telomere Length with Biomarkers and Disease-Related Composite Variables.

T/S Ratio correlated with plasma CRP, CSF sVCAM-1, and CSF NFL as well as Framingham CVD Risk, Framingham Stroke Risk, Beck Depression Inventory, Processing Speed, Motor Functioning, and Frailty/Pre-Frailty.