Gaardbo Julie C, Hartling Hans J, Gerstoft Jan, Nielsen Susanne D
Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, 2100 Copenhagen, Denmark.
Clin Dev Immunol. 2012;2012:670957. doi: 10.1155/2012/670957. Epub 2012 Mar 14.
Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) usually results in diminished viral replication, increasing CD4⁺ cell counts, a reversal of most immunological disturbances, and a reduction in risk of morbidity and mortality. However, approximately 20% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution. Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution in HIV infection, including mechanisms, relevance for clinical care, and possible solutions.
用高效抗逆转录病毒疗法（HAART）治疗HIV感染患者通常会导致病毒复制减少、CD4⁺细胞计数增加、大多数免疫紊乱得到逆转以及发病和死亡风险降低。然而，尽管病毒复制受到抑制，但所有HIV感染患者中约有20%未实现最佳免疫重建。这些患者被称为免疫无应答者（INR）。INR患者的免疫功能严重改变，包括淋巴细胞生成组织内细胞功能失常和产生减少、免疫调节因子（如调节性T细胞和Th17细胞）频率紊乱以及免疫激活、免疫衰老和细胞凋亡增加。重要的是，与具有最佳免疫重建的HIV感染患者相比，INR患者的发病和死亡风险增加。已经研究了可能改善免疫重建的HAART额外治疗方法，但迄今为止的结果令人失望。免疫无应答的原因尚未完全了解。本文总结了关于HIV感染中免疫重建不完全的已知和未知因素，包括机制、对临床护理的相关性以及可能的解决方案。
