Telomere length declines in persons living with HIV before antiretroviral therapy start but not after viral suppression: A longitudinal study over >17 years. Journal of Infectious Diseases
Telomere length (TL) shortens with age, and short TL is associated with coronary artery disease (CAD) and all-cause mortality in the general population. In people with HIV (PWH), associations of short TL with CAD events, metabolic syndrome, and neurocognitive impairment are reported. PWH have shorter TL and may have accelerated or accentuated aging and an increased risk of age-associated diseases compared with HIV-negative persons.
The aim of this study was to measure the rate of TL change during >3 years of untreated chronic HIV infection in participants of the Swiss HIV Cohort Study (SHCS) and to assess in these same PWH whether the rate of TL change continues to be affected during >3 years of suppressive ART.
The author team measured TL change in peripheral blood mononuclear cells by quantitative polymerase chain reaction in 107 Swiss HIV Cohort Study participants with longitudinal samples available both before and during suppressive ART. They obtained uni-/multivariable estimates for longitudinal TL dynamics including age, sex, and CD4/ CD8 ratio. Further, they assessed the effect of (1) individual antiretrovirals and (2) an individual TL-polygenic risk score (TL-PRS) based on 239 single-nucleotide polymorphisms on TL in 798 additional participants from our previous longitudinal studies.
During untreated HIV infection (median observation, 7.7; interquartile range [IQR], 4.7–11] years), TL declined significantly (median −2.12%/year; IQR, −3.48% to −0.76%/year; P = .002). During suppressive ART (median observation, 9.8; IQR, 7.1–11.1 years), there was no evidence of TL decline or increase (median+ 0.54%/year; IQR, −0.55% to + 1.63%/year; P = .329). The TL-PRS contributed to TL change (global P= .019) but particular antiretrovirals did not (all P > .15).
In conclusion, the study shows that TL declines significantly during almost 8 years of untreated HIV infection, with a significant association with an individual TL-PRS. Telomere length is stable during suppressive ART when measured longitudinally in the same participants, with no evidence of further TL decline or increase during almost 10 years after viral suppression. The effects of untreated HIV and suppressive ART on TL change appear large and thus clinically relevant. By contributing to TL preservation, suppressive ART may have a favorable effect on biological aging and the risk of aging-associated comorbidities in PWH.