Transplant Infectious Diseases Program, Department of Internal Medicine, University of Nebraska Medical Center, Lincoln, Nebraska 68198-5400, USA.
Biol Blood Marrow Transplant. 2012 May;18(5):731-8. doi: 10.1016/j.bbmt.2011.09.007. Epub 2011 Sep 29.
No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.
目前尚无针对腺病毒感染的特效治疗药物。我们描述了 13 例免疫功能低下的腺病毒感染患者接受 CMX001（西多福韦己氧基丙基酯）治疗的临床经验。CMX001 是一种口服生物利用的西多福韦脂质缀合物。我们对 13 例接受 CMX001 治疗的腺病毒疾病和病毒血症患者进行了回顾性分析；在开始使用 CMX001 治疗后，至少有 4 周的数据可用。病毒学反应（VR）定义为从基线下降 99%或血清中无法检测到腺病毒 DNA。该组的中位年龄为 6 岁（范围，0.92-66 岁）。1 例患者患有严重联合免疫缺陷，1 例患者为小肠移植受者，11 例患者为异基因干细胞移植受者。腺病毒病在移植后中位 75 天（范围，15-720 天）诊断。所有患者在接受 CMX001 治疗前中位接受静脉注射更昔洛韦 21 天（范围，5-90 天）。CMX001 起始时的绝对淋巴细胞计数中位数为 300 个/μL（范围，7-1500 个/μL）。8 例患者（61.5%）在治疗第一周后病毒载量下降≥1log10。到第 8 周，9 例患者（69.2%）表现出 VR，达到 VR 的中位时间为 7 天（范围，3-35 天）。仅在第 6 周时，绝对淋巴细胞计数的变化与对数 10 病毒载量的变化呈负相关（r=-0.74；P=0.03）。有 VR 的患者比没有 VR 的患者存活时间更长（中位时间 196 天与 54.5 天；P=0.04）。在治疗过程中，没有将 CMX001 的任何严重不良事件归因于 CMX001。CMX001 可能是治疗免疫功能低下的严重腺病毒病的一种有前途的治疗选择。
