We performed a systematic review and meta-analysis to investigate the impact of antiretroviral therapy (ART) on immune activation and reconstitution in people living with human immunodeficiency virus (PLWH). The PubMed electronic database and gray literature were searched from inception until March 2020. Studies were included if they reported the levels of immune activation and reconstitution at baseline and post-treatment. The random-effect model was used to calculate effect sizes. We included a total of ten studies comprising of 1 553 PLWH with an average age of 38.02 ± 10.10 years and a male/female ratio of 3.76. Pooled estimates showed a modest increase in the level of immune activation post-treatment (SMD: 0.64 [95% CI: -1.34, 2.63]; I2 = 98%, pH < 0.00001). In addition, treatment with ART significantly reconstituted the immune system (SMD: 0.70 [95% CI: 0.27, 1.44]; I2 = 68%, pH = 0.009). Notably, the level of immune reconstitution was independent of viral load or the treatment duration but dependent on the class of ARV drugs. Consequently, protease inhibitors were associated with the highest degree of immune restoration, followed by chemokine antagonists and lastly integrase inhibitors. In conclusion, immune activation persists in PLWH despite viral suppression and the degree of immune reconstitution is dependent on the drug class. Therefore, inclusion of protease inhibitors in ART may be of great benefit in immune restoration in patients with very low CD4 count.

中文翻译：

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成功的抗逆转录病毒疗法对 HIV 感染成人免疫激活和重建的影响：系统评价和荟萃分析。

我们进行了系统回顾和荟萃分析，以研究抗逆转录病毒疗法 (ART) 对人类免疫缺陷病毒 (PLWH) 感染者的免疫激活和重建的影响。从开始到 2020 年 3 月搜索了 PubMed 电子数据库和灰色文献。如果研究报告了基线和治疗后的免疫激活和重建水平，则包括在内。随机效应模型用于计算效应量。我们共纳入了 10 项研究，包括 1 553 名 PLWH，平均年龄为 38.02 ± 10.10 岁，男女比例为 3.76。汇总估计显示治疗后免疫激活水平适度增加（SMD：0.64 [95% CI：-1.34, 2.63]；I2 = 98%，pH < 0.00001）。此外，ART 治疗显着重建了免疫系统（SMD：0.70 [95% CI：0.27, 1.44]；I2 = 68%，pH = 0.009）。值得注意的是，免疫重建水​​平与病毒载量或治疗持续时间无关，但取决于 ARV 药物的类别。因此，蛋白酶抑制剂与最高程度的免疫恢复相关，其次是趋化因子拮抗剂，最后是整合酶抑制剂。总之，尽管病毒受到抑制，免疫激活在 PLWH 中持续存在，并且免疫重建的程度取决于药物类别。因此，在 ART 中加入蛋白酶抑制剂可能对 CD4 计数非常低的患者的免疫恢复有很大好处。蛋白酶抑制剂与最高程度的免疫恢复相关，其次是趋化因子拮抗剂，最后是整合酶抑制剂。总之，尽管病毒受到抑制，免疫激活在 PLWH 中持续存在，并且免疫重建的程度取决于药物类别。因此，在 ART 中加入蛋白酶抑制剂可能对 CD4 计数非常低的患者的免疫恢复有很大好处。蛋白酶抑制剂与最高程度的免疫恢复相关，其次是趋化因子拮抗剂，最后是整合酶抑制剂。总之，尽管病毒受到抑制，免疫激活在 PLWH 中持续存在，并且免疫重建的程度取决于药物类别。因此，在 ART 中加入蛋白酶抑制剂可能对 CD4 计数非常低的患者的免疫恢复有很大好处。