Departmento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México DF, México.
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lancet HIV. 2014 Nov;1(2):e60-7. doi: 10.1016/S2352-3018(14)70027-X. Epub 2014 Oct 21.
Immune reconstitution inflammatory syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in patients with HIV. IRIS is associated with an increased risk of admission to hospital and death. We assessed whether CCR5 blockade with maraviroc reduces the risk of IRIS.
The CADIRIS study was a double-blind, randomised, placebo-controlled trial that recruited participants from five clinical sites in Mexico and one in South Africa and followed them for 1 year. Patients were eligible if they were adults with HIV, who were naive to ART, had CD4 count lower than 100 cells per μL and HIV RNA greater than 1000 copies per mL. Participants were randomly assigned (1:1) by permuted block randomisation to receive either maraviroc (600 mg twice daily) or placebo in addition to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. Patients, care providers, and members of the research team were masked to treatment allocation. Clinical and laboratory evaluations were done at baseline, and weeks 2, 4, 8, 12, 16, 24, 48, and 60. The primary outcome was time to an IRIS event by 24 weeks. All patients who were randomly assigned contributed to the primary time-to-event analysis from the date of ART initiation until week 24, the time of an IRIS event or death. This trial is registered with ClinicalTrials.gov, number NCT00988780.
Between Dec 10, 2009, and Jan 17, 2012, we screened 362 patients; of whom 279 met the inclusion criteria and three refused to participate; thus 276 participants were randomly assigned (140 to receive maraviroc and 136 to receive placebo). 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc group and 31 (23%) in the placebo group (p=0·74). No difference in the time to IRIS events was noted between the treatment groups (HR 1·08, 95% CI 0·66-1·77; log-rank test p=0·74). 37 participants (26%) in the maraviroc group had grade 3 or 4 adverse events compared with 24 (18%) in placebo group; p=0·072); 25 (18%) in the maraviroc group and 21 (15%) in the placebo group had serious treatment emergent adverse events (p=0·63).
Maraviroc had no significant effect on development of IRIS after ART initiation. Inclusion of this CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in people with advanced HIV infection.
Pfizer.
免疫重建炎症综合征（IRIS）是接受抗逆转录病毒治疗（ART）的 HIV 患者的常见并发症。IRIS 与住院和死亡风险增加相关。我们评估了 CCR5 阻断剂马拉维若是否降低了 IRIS 的风险。
CADIRIS 研究是一项双盲、随机、安慰剂对照试验，在墨西哥的五个临床地点和南非的一个临床地点招募参与者，并随访 1 年。符合条件的患者为 HIV 初治、CD4 计数低于 100 个细胞/μL 且 HIV RNA 大于 1000 拷贝/ml 的成年患者。参与者按照 1:1 的比例通过随机分组接受马拉维若（600mg 每日两次）或安慰剂，同时接受包含替诺福韦、恩曲他滨和依非韦伦的 ART 方案治疗 48 周。患者、护理提供者和研究团队成员对治疗分配均不知情。在基线、第 2、4、8、12、16、24、48 和 60 周进行临床和实验室评估。主要结局为 24 周时发生 IRIS 事件的时间。所有随机分配的患者均从开始接受 ART 之日起至第 24 周（发生 IRIS 事件或死亡的时间）参与主要时间至事件分析。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00988780。
2009 年 12 月 10 日至 2012 年 1 月 17 日，我们筛选了 362 名患者；其中 279 名符合纳入标准，3 名拒绝参与；因此，276 名患者被随机分配（140 名接受马拉维若，136 名接受安慰剂）。64 名（23%）患者发生了 IRIS 事件，马拉维若组 33 名（24%），安慰剂组 31 名（23%）（p=0.74）。两组之间发生 IRIS 事件的时间无差异（HR 1.08，95%CI 0.66-1.77；对数秩检验 p=0.74）。马拉维若组 37 名（26%）患者发生 3 级或 4 级不良事件，安慰剂组 24 名（18%）（p=0.072）；马拉维若组 25 名（18%）和安慰剂组 21 名（15%）患者发生严重治疗后不良事件（p=0.63）。
ART 起始后，马拉维若对 IRIS 的发展没有显著影响。在晚期 HIV 感染患者的初始治疗方案中加入这种 CCR5 抑制剂并不能提供对 IRIS 发生的有意义的保护。
辉瑞。
