Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva. Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Laboratorio de Inmunovirologia, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
J Int AIDS Soc. 2020 Sep;23(9):e25607. doi: 10.1002/jia2.25607.
HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers.
We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model.
A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, CD4 T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% CI) = 2.573 (1.428 to 4.633)), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845)). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally, not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850).
This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure.
HIV 控制者在没有抗逆转录病毒治疗的情况下,能够自发地将病毒血症维持在低水平或无法检测到的水平。此外,HIV 控制者似乎比非 HIV 控制者具有更优越的自发清除丙型肝炎病毒(HCV)的能力。其中一些患者最终会失去 HIV 控制者的地位(短暂控制者),而一些 HIV 控制者则表现出持续的自然 HIV 控制(持续控制者)。我们旨在分析持续控制者是否比短暂控制者具有更优越的自发清除 HCV 的能力。
我们招募了 1981 年 1 月至 2016 年 10 月期间的 HIV 控制者,这些控制者具有可用的抗 HCV 抗体(抗-HCV)数据(n=744)。在具有抗-HCV 阳性(n=202 和 n=138)的持续和短暂 HIV 控制者中,分析了与 HIV 自发性控制相关的因素,与 1981 年 1 月至 2018 年 3 月期间招募的 1700 名 HCV 阳性非 HIV 控制者进行了比较,应用了双变量和多变量分析,遵循逻辑回归模型。此外,在 744 名患者中,还使用对数秩检验和 Kaplan-Meier 曲线探讨了与 HIV 控制者状态丧失和丧失时间相关的因素(n=744),在这种情况下,多变量分析包括 Cox 回归模型。
与非控制者(10.2%)相比,持续 HIV 控制者中自发清除 HCV 的频率更高(25.5%)。在调整了潜在的混杂因素,如性别、年龄、HIV 传播风险、CD4 T 细胞最低点和随访时间后,HCV 清除与持续的 HIV 自发性控制独立相关(p=0.002;OR(95%CI)=2.573(1.428 至 4.633)),但与短暂自发性控制无关(p=0.119;1.589(0.888 至 2.845))。此外,与短暂 HIV 控制者相比,持续 HIV 控制者更有可能自发清除 HCV(p=0.027;0.377(0.159 至 0.893))。最后,不丧失或延长失去这种控制的时间与 HCV 的自发清除独立相关(p=0.010;0.503(0.297 至 0.850))。
本研究表明,HIV 自发性持续控制与 HCV 自发性清除之间存在关联。研究结果支持在 HCV 自发性清除中涉及的持续 HIV 控制的免疫机制保存的观点。这些结果突出了持续的 HIV 控制者而不是短暂的控制者作为功能性 HIV 治愈的良好模型。