Telomere Length Declines In Persons Living With HIV Before Antiretroviral Therapy Start But Not After Viral Suppression: A Longitudinal Study Over >17 Years.

Schoepf, Isabella C; Thorball, Christian W; Ledergerber, Bruno; Kootstra, Neeltje A; Reiss, Peter; Raffenberg, Marieke; Engel, Tanja; Braun, Dominique L; Hasse, Barbara; Thurnheer, Christine; Marzolini, Catia; Seneghini, Marco; Bernasconi, Enos; Cavassini, Matthias; Buvelot, Hélène; Arribas, José R; Kouyos, Roger D; Fellay, Jacques; Günthard, Huldrych F and Tarr, Philip E (2022). Telomere Length Declines In Persons Living With HIV Before Antiretroviral Therapy Start But Not After Viral Suppression: A Longitudinal Study Over >17 Years. The journal of infectious diseases, 225(9), pp. 1581-1591. Oxford University Press 10.1093/infdis/jiab603

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BACKGROUND

In people living with HIV (PWH), long-term telomere length (TL) change without/with suppressive antiretroviral therapy (ART) and the contribution of genetic background to TL are incompletely understood.

METHODS

We measured TL change in peripheral blood mononuclear cells by quantitative PCR in 107 Swiss HIV Cohort Study participants with longitudinal samples available both before and during suppressive ART. We applied mixed effects multi-level regression to obtain uni-/multivariable estimates for longitudinal TL dynamics including age, sex, and CD4:CD8 ratio. We assessed the effect of individual antiretrovirals and of 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.

RESULTS

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=0.002). 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=0.329). TL-PRS contributed to TL change (global p=0.019) but particular antiretrovirals did not (all p>0.15).

DISCUSSION

In PWH, TL is associated with an individual polygenic risk score. TL declined significantly during untreated chronic HIV infection but no TL change occurred during suppressive ART.

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