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

被引:9
作者
Raffenberg, Marieke [1 ,2 ]
Engel, Tanja [1 ,3 ]
Schoepf, Isabella C. [1 ]
Kootstra, Neeltje A. [4 ]
Reiss, Peter [5 ,6 ,7 ]
Braun, Dominique L. [10 ]
Thorball, Christian W. [8 ,9 ,11 ]
Fellay, Jacques [8 ,9 ,11 ]
Kouyos, Roger D. [10 ,12 ]
Ledergerber, Bruno [10 ]
Guenthard, Huldrych F. [10 ,12 ]
Tarr, Philip E. [1 ]
机构
[1] Univ Basel, Kantonsspital Baselland, Univ Dept Med & Infect Dis Serv, CH-4101 Bruderholz, Switzerland
[2] Luzerner Kantonsspital, Dept Intens Care Med, Luzern, Switzerland
[3] Kantonsspital Uri, Dept Internal Med, Altdorf, Switzerland
[4] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Expt Immunol, Amsterdam, Netherlands
[5] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Global Hlth, Amsterdam, Netherlands
[6] Univ Amsterdam, Amsterdam Univ Med Ctr, Div Infect Dis, Amsterdam, Netherlands
[7] Amsterdam Inst Global Hlth & Dev, Amsterdam, Netherlands
[8] EPFL Sch Life Sci, Lausanne, Switzerland
[9] Swiss Inst Bioinformat, Lausanne, Switzerland
[10] Univ Zurich, Univ Hosp Zurich, Div Infect Dis, Zurich, Switzerland
[11] Univ Lausanne, Ctr Hosp Univ Vaudois, Precis Med Unit, Lausanne, Switzerland
[12] Univ Zurich, Inst Med Virol, Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
HIV infection; primary HIV infection; telomere length; multivariable analysis; antiretroviral therapy; HIV-1; INFECTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; IMMUNE SENESCENCE; HEART-DISEASE; NO EVIDENCE; INDIVIDUALS; BLOOD; RISK; THERAPY;
D O I
10.1093/infdis/jiab186
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1775 / 1784
页数:10
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