Background: Telomeres shorten over lifespan, and shorter leukocyte telomere length (LTL) is a marker of cellular aging associated with age-related physical morbidities, cognitive aging, and mortality. HIV infection and smoking are both associated with LTL cross-sectionally, but their influence on LTL over time is unclear. This study investigated the relative contribution of HIV and smoking on LTL dynamics in people living with HIV.
Methods: All non-pregnant girls and women ≥12 years old enrolled in the CARMA cohort with available blood specimens were included. For those with >1 sampling ≥1 year apart, the latest specimens were included in longitudinal sub-analyses. LTL was measured by multiplex qPCR. Possible predictors including age, ethnicity, smoking (current, past, never), HIV/viral load (VL) status (HIV-, HIV+/detectable VL, HIV+/undetectable VL), peak VL, and Hepatitis C virus status were considered for inclusion in multivariable models.
Results: LTL was obtained for 287 HIV+ and 211 HIV- participants aged 12-78 years, including 199 HIV+ and 49 HIV- with two specimens 1.0-7.9 years apart. In a cross-sectional multivariable regression, shorter LTL was associated with older age (ß=-0.35, p< 0.0001), current smoking (ß=-0.18, p=0.001) vs. never, and HIV+/detectable VL (ß=-0.13, p=0.004), but not HIV+/undetectable VL (ß=-0.06, p=0.17) vs. HIV-, after adjusting for ethnicity (n=450, R2=0.25). These results persisted in sensitivity analyses that either excluded ethnicity, restricted ethnicity to the largest group, or restricted age to ≥16 for consideration of smoking status. Longitudinally, LTL attrition rates were greater with current smoking (ß=-0.20, p=0.004) vs. never, but not associated with baseline HIV/VL status, after adjusting for baseline LTL (n=246, R2=0.11). HIV+ participants with detectable VL who became undetectable at follow-up were more likely to show an increase in LTL and vice-versa (n=57, Fisher''s exact test, p=0.043).
Conclusions: These analyses highlight the negative impact of current smoking on LTL, with an effect size larger than even uncontrolled HIV infection. These data suggest that LTL is better preserved in controlled HIV, and stress the importance of smoking cessation and controlling viremia to curb cellular aging.

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