Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK
Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK
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DOI：
10.1097/qad.0b013e328360a5a1
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发表时间：
2013-06-19
期刊：
影响因子：
3.8
通讯作者：
Easterbrook, Philippa J.
中科院分区：
文献类型：
--
作者：
Letang, Emilio;Lewis, James J.;Easterbrook, Philippa J.
Objectives：评估Kaposi肉瘤相关的反常免疫重建炎症综合征（KS-IRIS）在抗逆转录病毒治疗（ART）初治的HIV感染的Kaposi肉瘤患者中的发病率、预测因子和结局，这些患者在资源充足和资源有限的情况下启动ART。Design：汇总分析三个前瞻性队列的ART初治HIV感染的Kaposi肉瘤患者，来自撒哈拉以南非洲（SSA）和一个来自UK.Methods：KS-IRIS病例定义在不同地点进行标准化。考克斯回归和Kaplan-Meier生存分析被用来确定KS-IRIS和Kaposi肉瘤相关mortality.Results的发病率和预测因素：58 417（13.9%）合格的个人经历KS-IRIS的发病率高2.5倍，在非洲与欧洲队列（P=0.001）。ART单独作为初始卡波西肉瘤治疗（风险比2.97，95%置信区间（CI）1.02-8.69）; T1卡波西肉瘤分期（风险比2.96，95% CI 1.26-6.94）;血浆HIV-1 RNA水平大于5 log（10）拷贝/ml（风险比2.14，95%CI 1.25-3.67）可独立预测基线时的KS-IRIS。在评估的259例KSHV DNA患者中，可检测的血浆卡波西肉瘤相关疱疹病毒（KSHV）DNA还可预测KS-IRIS（风险比2.98，95% CI 1.23-7.19）。19名KS-IRIS患者死亡，均在SSA。非洲的卡波西肉瘤死亡率高3.3倍，KS-IRIS预测（风险比19.24，CI 7.62-48.58），缺乏化疗（风险比2.35，95% CI 1.09-5.05），ART前CD 4细胞计数小于200个细胞/l（危险比2.04，95% CI 0.99-4.2）和可检测的基线KSHV DNA（危险比2.12，95% CI 0.94-4.77）。这在很大程度上是由更晚期的卡波西肉瘤疾病和较低的化疗可用性解释的。KS-IRIS是非洲Kaposi肉瘤相关死亡率的主要贡献者。我们的研究结果支持需要提高对KS-IRIS的认识，鼓励早期介绍，转诊和诊断卡波西肉瘤，并倡导在非洲获得全身化疗。
Objectives:To assess the incidence, predictors, and outcomes of Kaposi sarcoma-associated paradoxical immune reconstitution inflammatory syndrome (KS-IRIS) in antiretroviral therapy (ART)-naive HIV-infected patients with Kaposi sarcoma initiating ART in both well resourced and limited-resourced settings.Design:Pooled analysis of three prospective cohorts of ART-naive HIV-infected patients with Kaposi sarcoma from sub-Saharan Africa (SSA) and one from the UK.Methods:KS-IRIS case definition was standardized across sites. Cox regression and Kaplan-Meier survival analysis were used to identify the incidence and predictors of KS-IRIS and Kaposi sarcoma-associated mortality.Results:Fifty-eight of 417 (13.9%) eligible individuals experienced KS-IRIS with an incidence 2.5 times higher in the African vs. European cohorts (P=0.001). ART alone as initial Kaposi sarcoma treatment (hazard ratio 2.97, 95% confidence interval (CI) 1.02-8.69); T1 Kaposi sarcoma stage (hazard ratio 2.96, 95% CI 1.26-6.94); and plasma HIV-1 RNA more than 5 log(10)copies/ml (hazard ratio 2.14, 95% CI 1.25-3.67) independently predicted KS-IRIS at baseline. Detectable plasma Kaposi sarcoma-associated herpes virus (KSHV) DNA additionally predicted KS-IRIS among the 259 patients with KSHV DNA assessed (hazard ratio 2.98, 95% CI 1.23-7.19). Nineteen KS-IRIS patients died, all in SSA. Kaposi sarcoma mortality was 3.3-fold higher in Africa, and was predicted by KS-IRIS (hazard ratio 19.24, CI 7.62-48.58), lack of chemotherapy (hazard ratio 2.35, 95% CI 1.09-5.05), pre-ART CD4 cell count less than 200cells/l (hazard ratio 2.04, 95% CI 0.99-4.2), and detectable baseline KSHV DNA (hazard ratio 2.12, 95% CI 0.94-4.77).Conclusion:KS-IRIS incidence and mortality are higher in SSA than in the UK. This is largely explained by the more advanced Kaposi sarcoma disease and lower chemotherapy availability. KS-IRIS is a major contributor to Kaposi sarcoma-associated mortality in Africa. Our results support the need to increase awareness on KS-IRIS, encourage earlier presentation, referral and diagnosis of Kaposi sarcoma, and advocate on access to systemic chemotherapy in Africa.