Clinic of Infectious Diseases, Department of Medicine and Science of Aging, University "G. d'Annunzio" Chieti-Pescara, Italy.
Unit of Immunodiagnostic and Molecular Pathology, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti- Pescara, Italy.
Curr HIV Res. 2021;19(3):260-268. doi: 10.2174/1570162X18666210111102046.
The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population.
Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10, IL1β, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation (T1), and 4 weeks after completing supplementation (T2).
In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the control group. The increase under Pidotimod treatment persisted after supplementation suspension, while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4 weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin C serum levels.
The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the analyzed times, as a secondary event to a remodulation of the immunological status obtained with pidotimod. This approach could represent a new way to design new intervention strategies aimed at improving the persistent immune activation status in the virologically suppressed HIV population.
HIV 感染治疗的改进和大量抗逆转录病毒药物的出现，导致 HIV 感染者的存活率提高，同时与普通人群相比，该人群因非艾滋病相关事件导致的发病率和死亡率上升。全身性炎症的增加和持续的免疫激活在决定非艾滋病合并症的高发病率方面起着关键作用。在过去的几年中，已经设计出许多通过不同机制起作用的天然或合成免疫调节分子。匹多莫德是一种具有免疫调节特性的合成二肽分子。本研究旨在评估匹多莫德补充对 HIV 感染者残留炎症的影响。
共纳入 40 名接受 cART 的 HIV 阳性个体：30 名接受匹多莫德补充治疗（研究组），10 名作为对照组（未接受匹多莫德补充）。所有参与者在入组时（T0）、匹多莫德补充 4 周后（T1）和补充完成后 4 周（T2）时，均检测胱抑素 C、PCR、ESR、微量白蛋白尿、TNF-α、IFN-γ、IL-4、IL-10、IL1β、IL-18 和 IL-2。
在接受匹多莫德治疗的 HIV 阳性患者中，细胞因子水平的评估显示，与对照组相比，IL-10、IFNγ和 IL-4 在入组时显著升高。补充停止后，匹多莫德治疗的增加持续存在，而促炎细胞因子水平降低。唾液 IgA 在补充的 4 周内也增加，并在补充完成后 4 周内持续增加。另一方面，胱抑素 C 和微量白蛋白尿水平随时间降低，血清胱抑素 C 水平降低更为明显。
研究结果表明，接受匹多莫德治疗的 HIV 人群实现了促炎和抗炎细胞因子的再平衡，以及胱抑素 C 水平的显著降低。治疗还允许在所有分析时间内增加唾液 IgA 水平，作为通过匹多莫德获得的免疫状态重塑的次要事件。这种方法可能代表一种新的方法来设计旨在改善病毒学抑制的 HIV 人群中持续免疫激活状态的新干预策略。
