HTB

HIV-associated reductions in telomere length are stopped by effective ART

Simon Collins, HIV i-Base

Results from a 17-year study report that untreated HIV is associated with significant reductions in telemere length (TL) but that effective ART stopped further damage. [1]

TL is associated with ageing, coronary artery disease (CAD) and all-cause mortality in the general population. In people living with HIV, TL has also been associated with metabolic syndrome, neurocognitive impairment and concerns about accelerated or accentuated ageing.

This was a longitudinal analysis from the Swiss HIV Cohort Study where 107 participants were followed for a minimum of three years before starting ART (median 7.7 years; IQR: 4.7 to 11) and for a minimum of three years after (median 9.8 years; IQR: 7.1 to 11.1).

Change in TL was measured in PBMCs by quantitative PCR and the analysis adjusted age, sex and CD4:CD8 ratio.

In the years before ART, TL significantly dropped by a median −2.12% per year (IQR, −3.48% to −0.76%), p=0.002. This compared to no significant changes when on suppressive ART: median change + 0.54% per year (IQR, −0.55% to + 1.63%) p=0.329.

No association was found between changes in TL and individual HIV drugs. However, an individual TL risk score based on 239 single-nucleotide polymorphisms identified in the group’s previous work did continue to correlate with reductions (global p=0.019).

comment

This impressive dataset reports both an under-appreciated concern of untreated ART and a benefit from suppressive ART that is large enough to likely have clinical significance.

It further supports the importance of universal ART on long-term health.

A poster just presented at CROI 2022 from the CHARTER study reported that TAF was associated with telomere shortening, but not tenofovir disoproxil. [2] 

This was in 121 HIV positive people initialling assessed from 2003–7 and again a median of 12 years later, but this had the significant limitation that baseline samples were not available on TAF because it was not yet available.

References

  1. Schoepf IC et al for the Swiss HIV Cohort Study. Telomere length declines in persons living with HIV before antiretroviral therapy start but not after viral suppression: a longitudinal study over >17 years. J Infect Dis. 2021 Dec 15:jiab603. doi: 10.1093/infdis/jiab603. (21 December 2021).
    https://pubmed.ncbi.nlm.nih.gov/34910812
  2. Upal R et al. Tenofovir alafenamide is associated with shorter telomere length in people with HIV. CROI 2022. Poster abstract 625.
    https://ww2.aievolution.com/cro2201/index.cfm?do=abs.viewAbs&abs=2431

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