Khanna Nina, Elzi Luigia, Mueller Nicolas J, Garzoni Christian, Cavassini Matthias, Fux Christoph A, Vernazza Pietro, Bernasconi Enos, Battegay Manuel, Hirsch Hans H
Division of Infectious Diseases & Hospital Epidemiology, University Hospital, University of Basel, Basel, Switzerland.
Clin Infect Dis. 2009 May 15;48(10):1459-66. doi: 10.1086/598335.
We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996.
From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007).
The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P = .007) but similar CD4+ T cell counts (60 vs. 71 cells/microL; P = .25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P < .001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/microL, 0.52; 95% CI, 0.32-0.85; P = .010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P = .006).
cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependent on cART use and baseline CD4+ T cell count.
我们调查了1996年联合抗逆转录病毒疗法（cART）引入前后，人类免疫缺陷病毒（HIV）感染者中进行性多灶性白质脑病（PML）的发病率及转归情况。
1988年至2007年期间，瑞士HIV队列研究共报告了226例PML病例。通过查阅病历，我们确认了186例病例，并记录了全因死亡率和PML所致死亡率。在生存分析中，排除了25例经尸检确诊的患者以及2例未进行CD4 + T细胞计数的患者，最终纳入159例患者（1996年前89例，1996 - 2007年期间70例）。
PML的发病率从1996年前的每100人年0.24例（95%置信区间[CI]，每100人年0.20 - 0.29例）降至1996年及以后的每100人年0.06例（95% CI，每100人年0.04 - 0.10例）。与1996年或之后确诊的患者相比，1996年前确诊的患者既往获得性免疫缺陷综合征定义疾病的发生率更高（P = 0.007），但CD4 + T细胞计数相似（分别为60个/微升和71个/微升；P = 0.25）。PML所致死亡的中位时间为71天（四分位间距，44 - 140天），而全因死亡的中位时间为90天（四分位间距，54 - 313天）。PML所致的1年死亡率从cART治疗前时代的每100人年82.3例（95% CI，每100人年58.8 - 115.1例）降至cART治疗时代的每100人年37.6例（95% CI，每100人年23.4 - 60.5例）。在多变量模型中，cART是与PML所致较低死亡率相关的唯一因素（风险比，0.18；95% CI，0.07 - 0.50；P < 0.001），而全因死亡率与基线CD4 + T细胞计数（每增加100个/微升的风险比，0.52；95% CI，0.32 - 0.85；P = 0.010）和cART的使用（风险比，0.37；95% CI，0.19 - 0.75；P = 0.006）相关。
无论基线CD4 + T细胞计数如何，cART均可降低发病率和PML所致的1年死亡率，而总体死亡率则取决于cART的使用和基线CD4 + T细胞计数。
