Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Malattie Infettive, Largo Agostino Gemelli 8, 00168 Roma, Italia.
Dipartimento di Sicurezza e Bioetica, Università Cattolica del Sacro Cuore, Roma, Italia.
J Antimicrob Chemother. 2023 Sep 5;78(9):2315-2322. doi: 10.1093/jac/dkad237.
Blood telomere length (BTL) is a validated biomarker of aging. ART reduces immunosenescence and has benefits in terms of BTL in people living with HIV (PLWH). However, it has also been observed that ART containing NRTIs, such as tenofovir or abacavir, which are potent inhibitors of human telomerase activity in vitro, might negatively affect BTL. Here we investigated the effects on BTL 1 year after switching to a dual therapy (DT) with dolutegravir + lamivudine versus maintaining a standard triple therapy (TT) with a two-NRTI backbone and an anchor drug.
This was a longitudinal, prospective, matched, controlled study that included virologically suppressed adults on stable three-drug ART who either switched at baseline (BL) to DT or maintained TT. The DT and TT groups were 1:1 matched for age, sex, years since HIV diagnosis, years on ART and anchor drug. BTL was assessed by a monochrome multiplex qPCR at BL and after 48 weeks (W48).
We enrolled 120 PLWH, i.e. 60 participants in each group. At BL, the BTL means were comparable between the two groups (P = 0.973). At W48, viro-immunological status was stable and an overall increase in the mean BTL was observed, i.e., +0.161 (95%CI, 0.054-0.268) (P = 0.004). However, the within-group analysis showed a significant mean BTL gain in the DT group (P = 0.003) but not in the TT group (P = 0.656).
In this setting of virologically suppressed PLWH, simplifying to dolutegravir + lamivudine was associated with a higher gain in BTL than maintaining triple therapy after the 1 year follow-up. These findings suggest that as a simplification strategy dolutegravir + lamivudine might have a positive effect on BTL.
血液端粒长度（BTL）是衰老的验证生物标志物。抗逆转录病毒疗法（ART）可减少免疫衰老，并在艾滋病毒感染者（PLWH）的 BTL 方面具有益处。然而，也有观察到包含 NRTIs 的 ART，如替诺福韦或阿巴卡韦，在体外是人类端粒酶活性的有效抑制剂，可能会对 BTL 产生负面影响。在这里，我们研究了在改用含有度鲁特韦和拉米夫定的双疗法（DT）与维持含有两种 NRTI 骨干和锚定药物的标准三联疗法（TT）一年后对 BTL 的影响。
这是一项纵向、前瞻性、匹配、对照研究，纳入了病毒学抑制的稳定三药 ART 成年患者，他们要么在基线（BL）时切换到 DT，要么维持 TT。DT 和 TT 组在年龄、性别、HIV 诊断后年限、ART 年限和锚定药物方面 1:1 匹配。在 BL 和 48 周（W48）时通过单彩色多重 qPCR 评估 BTL。
我们招募了 120 名 PLWH，即每组 60 名参与者。在 BL 时，两组的 BTL 平均值相当（P=0.973）。在 W48 时，病毒免疫状态稳定，平均 BTL 总体增加，即+0.161（95%CI，0.054-0.268）（P=0.004）。然而，组内分析显示 DT 组的平均 BTL 明显增加（P=0.003），而 TT 组则没有（P=0.656）。
在这种病毒学抑制的 PLWH 环境中，简化为度鲁特韦+拉米夫定与维持三联疗法相比，在 1 年随访后 BTL 增加更多。这些发现表明，作为一种简化策略，度鲁特韦+拉米夫定可能对 BTL 产生积极影响。
