Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Esther Møllers Vej 6, 2100, Copenhagen Ø, Denmark.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Curr HIV/AIDS Rep. 2018 Apr;15(2):162-171. doi: 10.1007/s11904-018-0387-y.
Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions.
Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function. HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.
通过早期诊断和抗逆转录病毒治疗（ART）的启动，可以实现 HIV 的最佳控制。最近发表了两项大型随机试验（TEMPRANO 和 START），记录了早期开始 ART 对 HIV 阳性成年人的临床益处。主要发现进行了综述，重点关注严重非艾滋病（SNA）疾病。
两项试验的数据表明，在 HIV 感染过程中早期开始 ART 可显著降低机会性疾病和侵袭性细菌感染的风险。这表明 HIV 在早期感染时引起免疫损伤，通过控制病毒复制可以得到纠正。有趣的是，在 START 中，观察到癌症（包括与感染相关和不相关的癌症）的风险显著降低。与机会性感染的发现一样，早期 ART 的这种抗癌作用表明免疫系统如何影响重要的致癌过程。在 START 中，还有一些证据表明早期 ART 启动可保留肾功能，尽管其临床后果尚不清楚。相反，尽管没有明显的不良反应，但这些试验并未显示出对代谢相关疾病结局、肺部疾病或神经认知功能的明显影响。HIV 在感染后不久就会引起免疫损伤。ART 至少部分地逆转了这种损害。免疫损伤的生物学性质需要进一步阐明，以及先天免疫激活的机制和临床影响。基于 TEMPRANO 和 START 的发现，并且由于 ART 降低了传播的风险，ART 的启动应该在所有 HIV 诊断后提供给所有人。
