Impact of Delaying Antiretroviral Treatment During Primary Human Immunodeficiency Virus Infection on Telomere Length

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.

Telomere Length Declines in Persons With Human Immunodeficiency Virus Before Antiretroviral Therapy Start but Not After Viral Suppression: A Longitudinal Study Over >17 Years

“…Prior evidence has suggested that TL is shorter in PWH compared to the general population. Our study confirms and extends previous reports by others [17,18] and us [19] that have shown significant TL decline occurring during HIV seroconversion [17,18], with ART initiation delay during primary HIV infection [19], and during untreated or suboptimally treated chronic HIV infection [33].…”

“…A 2.12% annual TL decline during untreated HIV might translate into 11% shorter TL over 5 years. This compares to 8.2% shorter TL (the effect of being 10 years older) and 17%-22% shorter TL (the effect of delayed ART start during primary HIV infection) in our previous study in Swiss PWH [19]. In addition, a 2.8-fold shorter TL was associated with an approximately twofold increased coronary artery disease event risk in Swiss PWH [3].…”

“…Telomere length. We measured TL by quantitative PCR in stored peripheral blood mononuclear cells (PBMCs), and used as control the single copy albumin gene, as previously reported [8,19] (Supplementary Methods). We report TL values as relative values expressed as the T/S ratio (amplification of the telomere product/amplification of the single copy albumin gene).…”

“…A large proportion of TL shortening in PWH may occur early during HIV infection, particularly during HIV seroconversion [17,18]. We recently reported that delaying antiretroviral therapy (ART) start in primary HIV infection for a matter of weeks is associated with significant and sustained TL shortening, compared to early ART start [19].…”

Ageing with HIV: Challenges and biomarkers

“… 63 This positive effect of ART on TL, diminishes when ART initiation is delayed. 64 Likely, this deceleration in TL recovery despite successful ART is hampered by the extension of initial damage. The ART benefit on TL is maintained in long-term treated aviremic HIV-infected adults, although more longitudinal studies are needed to confirm it.…”