Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory for HIV/AIDS Research, Beijing, China.
J Leukoc Biol. 2020 Apr;107(4):597-612. doi: 10.1002/JLB.4MR1019-189R. Epub 2020 Jan 22.
The morbidity and mortality of HIV type-1 (HIV-1)-related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV-1 replication and gradual recovery of CD4 T-cell counts. However, ∼10-40% of HIV-1-infected individuals fail to achieve normalization of CD4 T-cell counts despite persistent virological suppression. These patients are referred to as "inadequate immunological responders," "immunodiscordant responders," or "immunological non-responders (INRs)" who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non-AIDS events and present higher rates of mortality than HIV-1-infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV-1-infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.
由于高效抗逆转录病毒疗法的引入，HIV 型-1（HIV-1）相关疾病的发病率和死亡率显著降低，该疗法可诱导 HIV-1 复制的持续抑制和 CD4 T 细胞计数的逐渐恢复。然而，约 10-40%的 HIV-1 感染者尽管病毒学抑制持续存在，但未能实现 CD4 T 细胞计数的正常化。这些患者被称为“免疫应答不足者”、“免疫不一致应答者”或“免疫无应答者（INRs）”，他们表现出严重的免疫功能障碍。事实上，INRs 发生 AIDS 和非 AIDS 事件临床进展的风险增加，死亡率高于 CD4 T 细胞免疫重建充分的 HIV-1 感染者。迄今为止，HIV-1 感染者不完全免疫重建的潜在机制尚未完全阐明。鉴于这一局限性，深入了解免疫重建的机制并设计有效的个体化治疗策略具有重要的实际意义。因此，在这篇综述中，我们旨在强调不完全免疫重建的机制和风险因素，以及干预策略。
