The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease
The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease
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DOI：
10.1093/annonc/mdn697
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发表时间：
2009-04-01
影响因子：
50.5
通讯作者：
Bower, M.
中科院分区：
文献类型：
--
作者：
Powles, T.;Stebbing, J.;Bower, M.
背景资料：在艾滋病毒队列中，获得高效抗逆转录病毒治疗（HAART），卡波西肉瘤（KS）的发病率下降，但是，多中心Castleman病（MCD）在HIV的发病率没有以前被描述。方法：艾滋病毒相关MCD的发病率计算从一个前瞻性的艾滋病毒数据库与56 202患者年的后续行动，并与KS相比。进行单变量和多变量分析，以确定与MCD相关的因素。在新诊断的MCD（n = 24）、KS（n = 72）、HIV相关淋巴瘤（n = 74）和HIV阳性对照（n = 53）的HIV血清阳性个体中测量血浆人类疱疹病毒（HHV）-8 DNA水平。在24例HIV相关MCD病例中，测量的发生率为4.3/10 000患者-年[95%置信区间（CI）2.7-6.4]。HAART前的发病率（1983-1996），早期-HAART（1997-2001）及之后的HAART（2002-2007）年代为2.3（95% CI 0.02-4.2），2.8（95% CI 0.9-6.5）和8.3（95% CI 4.6-12.6），代表随时间统计学显著增加（P < 0.05）。相比之下，从1180例KS病例中，该队列的发病率随时间推移而下降。多变量分析表明，CD 4计数最低值> 200/mm（3）、年龄增加、既往无HAART暴露和非高加索种族均与MCD风险增加相关。新诊断MCD患者血浆HHV-8 DNA水平高于KS、淋巴瘤和HIV阳性对照（Mann-Whitney U检验，P < 0.0001）。它似乎更频繁地发生在免疫功能保存良好的老年HIV阳性个体中。
Background: In HIV cohorts with access to highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) is falling; however, the incidence of multicentric Castleman's disease (MCD) in HIV has not previously been described.Methods: The incidence of HIV-associated MCD was calculated from a prospective HIV database with 56 202 patient-years of follow-up and compared with KS. Univariate and multivariate analyses were carried out to identify factors associated with MCD. Plasma human herpesvirus (HHV)-8 DNA levels were measured in HIV-seropositive individuals with newly diagnosed MCD (n = 24), KS (n = 72), HIV-associated lymphoma (n = 74) and HIV-positive controls (n = 53).Results: From 24 cases of HIV-associated MCD, the incidence measured 4.3/10 000 patient-years [95% confidence interval (CI) 2.7-6.4]. The incidence in the pre-HAART (1983-1996), early-HAART (1997-2001) and later HAART (2002-2007) eras were 2.3 (95% CI 0.02-4.2), 2.8 (95% CI 0.9-6.5) and 8.3 (95% CI 4.6-12.6), respectively, representing a statistically significant increase over time (P < 0.05). In contrast, from 1180 cases of KS, the incidence in this cohort decreased with time. Multivariate analysis demonstrated that a nadir CD4 count > 200/mm(3), increased age, no previous HAART exposure and non-Caucasian ethnicity were all associated with an increased risk of MCD. Plasma HHV-8 DNA levels were higher in patients with newly diagnosed MCD than with KS, lymphomas or HIV-positive controls (Mann-Whitney U-test, P < 0.0001).Conclusions: The incidence of HIV-associated MCD is increasing. It appears to occur more frequently in older HIV-positive individuals with well-preserved immune function.