Solomon Ajantha, Tennakoon Surekha, Leeansyah Edwin, Arribas Jose, Hill Andrew, Van Delft Yvon, Moecklinghoff Christiane, Lewin Sharon R
Department of Infectious Diseases, Monash University and Alfred Health, Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
PLoS One. 2014 Nov 4;9(11):e109718. doi: 10.1371/journal.pone.0109718. eCollection 2014.
To determine whether nucleos(t)ide reverse transcriptase inhibitors (NRTI) contribute to an accelerated loss in telomere length (TL) in HIV-infected patients on antiretroviral therapy (ART).
Substudy of randomised controlled trial.
Patients with HIV RNA <50 copies/mL on combination ART (n = 256) were randomised to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 127) or with 2 NRTIs (n = 129) for up to 144 weeks. TL and telomerase activity was quantified on stored peripheral blood mononuclear cells (PBMC; n = 124) using quantitative real time PCR.
Patients in the sub-study had a mean age of 44 years and had received NRTI for a mean of 6.4 years (range 1-20 years). As expected, older patients have significantly shorter TL (p = 0.006), while women had significantly longer TL (p = 0.026). There was no significant association between TL and either the duration of prior NRTI treatment (p = 0.894) or the use of a PI versus NNRTI (p = 0.107). There was no significant difference between patients who continued or ceased NRTI in the mean change/year of TL or telomerase (p = 0.580 and 0.280 respectively).
Continuation versus cessation of NRTI treatment was not associated with an accelerated loss in TL or telomerase activity.
确定核苷（酸）逆转录酶抑制剂（NRTI）是否会导致接受抗逆转录病毒治疗（ART）的HIV感染患者端粒长度（TL）加速缩短。
随机对照试验的子研究。
接受联合抗逆转录病毒治疗且HIV RNA<50拷贝/mL的患者（n = 256）被随机分为两组，一组接受每日一次800/100mg的达芦那韦/利托那韦（DRV/r），作为单一疗法（n = 127），另一组联合两种NRTI（n = 129），治疗长达144周。使用定量实时PCR对储存的外周血单个核细胞（PBMC；n = 124）中的TL和端粒酶活性进行定量分析。
该子研究中的患者平均年龄为44岁，接受NRTI的平均时间为6.4年（范围1 - 20年）。正如预期的那样，年龄较大的患者TL显著较短（p = 0.006），而女性的TL显著较长（p = 0.026）。TL与既往NRTI治疗的持续时间（p = 0.894）或蛋白酶抑制剂（PI）与非核苷类逆转录酶抑制剂（NNRTI）的使用之间均无显著关联（p = 0.107）。继续或停止使用NRTI的患者在TL或端粒酶的年均变化方面无显著差异（分别为p = 0.580和0.280）。
继续或停止使用NRTI治疗与TL或端粒酶活性的加速丧失无关。
