Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion.

Janice M Leung,Michael Kobor,Steve Horvath,M-J Milloy,Stella Xu,Julio Montaner,P Richard Harrigan,Kanna Hayashi,Nick Fishbane,Julie Macisaac,S.F Paul Man,Meaghan Jones,Alexander Morin,Joseph Cy Liu,Don D Sin

doi:10.18632/aging.101184

Abstract

Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

Highlights

With the benefit of combination antiretroviral therapy, persons living with human immunodeficiency virus (PLWH) have survived to older ages [1, 2] with fewer opportunistic infections and AIDS-defining cancers [3, 4]
In this study investigating longitudinal blood samples of IDUs who subsequently contracted human immunodeficiency virus (HIV), we found an acute telomere shortening signal in the immediate postseroconversion period
Telomere length subsequently stabilized in the post-seroconversion period with no significant changes observed between the T2 and T3 time points

Summary

INTRODUCTION

With the benefit of combination antiretroviral therapy (cART), persons living with human immunodeficiency virus (PLWH) have survived to older ages [1, 2] with fewer opportunistic infections and AIDS-defining cancers [3, 4]. PLWH appear to have shorter peripheral blood telomere lengths compared with uninfected individuals [10,11,12], yet whether this represents a gradual attrition over the course of HIV infection or an abrupt shortening during periods of acute illness and profound immunosuppression has not been established It has been shown in a cohort of cART-treated, virally suppressed PLWH that while telomere length, a surrogate marker of cellular aging, is shorter in PLWH www.aging‐us.com compared with HIV-uninfected individuals, the slope of telomere length vs age is no different between the two groups [11]. We demonstrate for the first time that changes in surrogate aging biomarkers may be observed shortly after HIV infection

RESULTS

DISCUSSION

MATERIALS AND METHODS