HIV-associated reductions in telomere length are stopped by effective ART
7 February 2022. Related: Coinfections and complications, Basic science and immunology, Ageing and life expectancy.
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
- 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 - Upal R et al. Tenofovir alafenamide is associated with shorter telomere length in people with HIV. CROI 2022. Poster abstract 625.
https://www.croiconference.org/abstract/tenofovir-alafenamide-is-associated-with-shorter-telomere-length-in-people-with-hiv/