Mitchell S M, Membrey W L, Youle M S, Obi A, Worrell S, Gazzard B G
Department of Ophthalmology, St Stephen's Centre, Chelsea and Westminster Hospital, London.
Br J Ophthalmol. 1999 Jun;83(6):652-5. doi: 10.1136/bjo.83.6.652.
BACKGROUND/AIMS: There have been several recent reports suggesting that the natural history of cytomegalovirus retinitis (CMVR) has been significantly modified with the development of highly active antiretroviral therapy (HAART). This 2 year prospective cohort study assesses the effect of HAART on the incidence and progression of CMV retinitis in patients with CD4 cell counts below 50 cells x10(6)/l.
63 patients, with CD4 cell counts below 50 cells x10(6)/l, who were recruited to a 2 year prospective cohort study at the commencement of combination antiretroviral therapy including the use of the proteinase inhibitor, indinavir, were reported. The response to HAART was assessed in terms of a rise in the CD4 cell count and fall in HIV viral load. An experienced ophthalmologist performed dilated funduscopy at the time of recruitment and thereafter at 2 weekly intervals and retinal photography was performed at monthly intervals in patients with CMVR. The activity and progression of CMV retinitis was assessed on the basis of the characteristic clinical and photographic findings.
34 patients achieved at least 50 CD4 cells x10(6)/l at 3 months after initiation of therapy. New diagnoses of CMVR were seen only in the non-responder group (p=0. 085). Overall, the relative risk of a new retinitis event in this group was 3.52 (95% CI 1.16, 10.68) at 3 months compared with those patients who were responsive to HAART. 12 of the 63 patients had previous CMVR. Disease progression was associated with non-response to therapy (p=0.182 exact). In patients with CMVR the median time to first progression was 18 days (95% CI 8, 91) in non-responders and 121 days (95% CI 0.59, 3.65) in responders. By the end of the 2 year follow up period all surviving patients had >50 CD4 cells x10(6)/l. No CMV events were seen after 8 months of therapy in either group of patients.
These findings suggest that significant clinical immunorestoration to CMV occurs in response to HAART in patients with CMVR after a lag time of 3-8 months. Initially, a rise in CD4 count is predictive of CMVR response but after the lag period all survivors appear to have developed a clinical immunorestoration to CMV. If HAART is commenced in at risk patients before the development of CMVR the incidence of new disease falls significantly.
背景/目的：最近有几份报告表明，随着高效抗逆转录病毒疗法（HAART）的发展，巨细胞病毒性视网膜炎（CMVR）的自然病程已发生显著改变。这项为期2年的前瞻性队列研究评估了HAART对CD4细胞计数低于50个细胞×10⁶/L的患者中CMV视网膜炎的发病率和进展的影响。
报告了63例CD4细胞计数低于50个细胞×10⁶/L的患者，他们在开始联合抗逆转录病毒疗法（包括使用蛋白酶抑制剂茚地那韦）时被纳入一项为期2年的前瞻性队列研究。根据CD4细胞计数的升高和HIV病毒载量的下降来评估对HAART的反应。一名经验丰富的眼科医生在招募时进行散瞳眼底检查，此后每2周进行一次，对于患有CMVR的患者，每月进行一次视网膜摄影。根据特征性的临床和摄影结果评估CMV视网膜炎的活动和进展。
34例患者在开始治疗3个月后CD4细胞计数至少达到50个细胞×10⁶/L。仅在无反应组中发现了新诊断的CMVR（p = 0.085）。总体而言，与对HAART有反应的患者相比，该组在3个月时发生新视网膜炎事件的相对风险为3.52（95%可信区间1.16，10.68）。63例患者中有12例曾患CMVR。疾病进展与对治疗无反应相关（确切p = 0.182）。在患有CMVR的患者中，无反应者首次进展的中位时间为18天（95%可信区间8，91），有反应者为121天（95%可信区间0.59，3.65）。到2年随访期结束时，所有存活患者的CD4细胞计数均>50个细胞×10⁶/L。两组患者在治疗8个月后均未出现CMV事件。
这些发现表明，在患有CMVR的患者中，HAART治疗后3至8个月的延迟期后，对CMV出现了显著的临床免疫恢复。最初，CD4计数的升高可预测CMVR反应，但在延迟期后，所有幸存者似乎都对CMV产生了临床免疫恢复。如果在有风险的患者中在CMVR发生之前开始HAART，新疾病的发病率会显著下降。
