NEJM：在HIV感染早期进行治疗能够延缓免疫系统受损

在一项新的临床试验中，研究人员发现在HIV感染早期阶段进行为期48周的抗逆转录病毒药物治疗能够延缓对人免疫系统的损伤，因而延缓开始进行终生抗逆转录病毒药物治疗的需求。不过，相对于这些志愿者参与这项治疗所花的时间，这种延缓时间还不是显着性的长。相关研究结果于2013年1月17日发表在New England Journal of Medicine期刊上，论文标题为"Short-Course Antiretroviral Therapy in Primary HIV Infection"。

除非经常去检查，不然大多数人在他们感染上HIV病毒后最初几年内并不会意识到他们是HIV阳性的。然而，人们的免疫系统从不会成功地清除掉HIV病毒，相反，这种病毒躲藏起来，缓慢地削弱身体的防御机制和破坏CD4 T细胞，其中这种T细胞在免疫反应种发挥着关键性的作用。

如果没有接受治疗，那么免疫系统遭受越来越多的破坏，让个人有日益增加的风险患上其他的危及生命的感染。为了阻止这种情形发生，当体内剩下来的CD4 T细胞数量达到每立方毫米350个细胞的水平时，根据国际治疗指南，医生们就得建议个人进行终生的抗逆转录病毒药物治疗。这些药物不仅阻止进一步损伤免疫系统，而且也允许它进行自我修复。

几项观察性研究已提示着在HIV感染发生的时刻进行治疗能够延缓免疫系统受损的程度和速度，因而也就延缓开始进行终生抗逆转录病毒药物治疗的需求。血清HIV阳转期间短期抗逆转录治疗(Short Pulse Anti-Retroviral Therapy at HIV Seroconversion， SPARTAC)是第一个大型的随机对照试验来测试这种猜测。这项试验已开展5年多，涉及来自澳大利亚、巴西、冰岛、意大利、南非、西班牙、乌干达和英国的366名成年人。

在SPARTAC试验中，所有的试验志愿者在被HIV感染的6个月内经测试而被鉴定出，并接受随机分为三组：第一组接受为期48周的抗逆转录病毒药物治疗，第二组接受为期12周的抗逆转录病毒药物治疗，第三组不接受药物治疗。研究人员然后测量每名志愿者的CD4 T细胞数量降到每立方毫米350个细胞以下和/或他们开始进行终生抗逆转录病毒药物治疗时所需的时间。

在这项研究中，研究人员发现没有接受药物治疗的试验志愿者在感染HIV病毒平均157周后就得开始接受终生抗逆转录病毒药物治疗。而平均而言，那些接受为期12周的抗逆转录病毒药物治疗的志愿者在感染HIV病毒平均184周后开始接受终生抗逆转录病毒药物治疗(延缓27周，但是研究人员并不认为这种影响是显着性的)。

然而，那些接受为期48周的抗逆转录病毒药物治疗的志愿者在感染HIV病毒平均222周后开始接受终生抗逆转录病毒药物治疗，即延缓65周。相比于不接受药物治疗或接受为期12周的抗逆转录病毒药物治疗，这代表着一种重要的延缓，但是总体而言，相对于这些志愿者参与这项治疗所花的时间，这种延缓时间还不是显着性的长。

此外，在这项研究的整个时间内，相比于另外两组志愿者，接受为期48周的抗逆转录病毒药物治疗的那组志愿者拥有更高的CD4 T细胞数量，因而潜在地降低遭受诸如肺结核之类的继发性感染的风险。而且相对于其他的志愿者，在停止治疗一年多后，他们的血液中的HIV水平也更低，因而这就能够降低将HIV病毒传染到性伴侣的风险。

DOI: 10.1056/NEJMoa1110039
PMC:
PMID:

Short-Course Antiretroviral Therapy in Primary HIV Infection

The SPARTAC Trial Investigators

BACKGROUND Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P=0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P=0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P=0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log10copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number,ISRCTN76742797, and EudraCT number, 2004-000446-20.)