Impact of Delaying Antiretroviral Treatment During Primary Human Immunodeficiency Virus Infection on Telomere Length.
HIV infection
antiretroviral therapy
multivariable analysis
primary HIV infection
telomere length
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
22 11 2021
22 11 2021
Historique:
received:
15
12
2020
accepted:
31
03
2021
pubmed:
7
4
2021
medline:
1
10
2022
entrez:
6
4
2021
Statut:
ppublish
Résumé
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). We measured TL in peripheral blood mononuclear cells by quantitative polymerase chain reaction in participants of the Zurich PHI Study with samples available for ≥6 years. We obtained univariable/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL. In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the first (shortest), second, and third (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (P for trend = .034), and longer TL over 6 years, but only with continuous ART (P < .001), not if ART was interrupted ≥12 months (P = .408). In multivariable analysis, participants in the second and third ART delay tertile had 17.6% (5.4%-29.7%; P = .004) and 21.5% (9.4%-33.5%; P < .001) shorter TL, after adjustment for age, with limited effect modification by clinical variables. In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.
Sections du résumé
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 polymerase chain reaction in participants of the Zurich PHI Study with samples available for ≥6 years. We obtained univariable/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 first (shortest), second, and third (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (P for trend = .034), and longer TL over 6 years, but only with continuous ART (P < .001), not if ART was interrupted ≥12 months (P = .408). In multivariable analysis, participants in the second and third ART delay tertile had 17.6% (5.4%-29.7%; P = .004) and 21.5% (9.4%-33.5%; P < .001) shorter TL, after adjustment for age, with limited effect modification by clinical variables.
CONCLUSIONS
In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.
Identifiants
pubmed: 33822976
pii: 6211111
doi: 10.1093/infdis/jiab186
doi:
Substances chimiques
Anti-Retroviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1775-1784Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.