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The impact of chronic and latent viral infections on aging in people living with HIV Yang, Yi


Background: Over 38 million people are currently living with HIV. Despite antiretroviral therapies that have increased lifespan, people living with HIV (PLWH) experience faster cellular and immunological aging relative to their HIV-negative peers. Infection with chronic/latent viruses such as herpesviruses and hepatitis viruses may accelerate immunological aging. Individually, these viruses are associated with aging markers and/or age-associated diseases, but their cumulative effect is unknown. We characterized the number and type of seven non-HIV chronic/latent viruses in PLWH and those not living with HIV and investigated associations with leukocyte telomere length (LTL). Methods: A total of 187 PLWH (105F/82M) and 189 HIV-negative controls (105F/84M) were selected and balanced for each decade of age, sex, and HIV group. Past CMV, EBV, HHV-8, HSV-1, and HSV-2 infection was determined serologically; HIV, HCV, and HBV were self-reported. Relative LTL was measured using qPCR. Associations between number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modelling. Results: PLWH had significantly more non-HIV viruses than HIV-negative controls (p<0.0001), as did females compared to males (p<0.0001). In multivariable analyses, HIV-positive status, female sex, Indigenous ethnicity, current smoking, and African region of birth were independently associated with a greater frequency of viral infection. Additionally having 3-4 viruses (vs. 0-2) was independently associated with shorter LTL. While no individual non-HIV virus had a significant effect on LTL, some virus combinations were independently associated with shorter or longer LTL. Furthermore, sex-segregated analyses revealed that female and male participants differed with respect to factors associated with both total virus burden and LTL. Conclusions: Our results suggest that carrying a greater number of persistent viruses contributes to immunological aging, with specific viruses and combinations exerting differential effects based on sex. Future studies to better understand the contribution of chronic/latent viral infection on immunological aging and clinical outcomes can shed light on the potential value of viral prevention or treatment initiatives. Such studies when combined with biological and sociocultural considerations between men and women in the context of virus acquisition risk can help us understand how to improve the health lifespan of all populations.

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