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Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length


Raffenberg, Marieke; Engel, Tanja; Schoepf, Isabella C; Kootstra, Neeltje A; Reiss, Peter; Braun, Dominique L; Thorball, Christian W; Fellay, Jacques; Kouyos, Roger D; Ledergerber, Bruno; Günthard, Huldrych F; Tarr, Philip E; Zurich Primary HIV Infection Study; Swiss HIV Cohort Study (2021). Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length. Journal of Infectious Diseases:Epub ahead of print.

Abstract

BACKGROUND

Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI).

METHODS

We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for >6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL.

RESULTS

In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p<0.001), not if ART was interrupted >12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p<0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables.

DISCUSSION

In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

Abstract

BACKGROUND

Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI).

METHODS

We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for >6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL.

RESULTS

In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p<0.001), not if ART was interrupted >12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p<0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables.

DISCUSSION

In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:5 April 2021
Deposited On:14 Oct 2021 07:16
Last Modified:14 Oct 2021 07:16
Publisher:Oxford University Press
ISSN:0022-1899
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/infdis/jiab186
PubMed ID:33822976

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