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基线CD4+ T细胞计数可预测拉米夫定耐药的乙肝病毒感染患者(无论有无HIV感染)接受阿德福韦治疗后的乙肝病毒动力学。

Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection.

作者信息

Cortez K J, Proschan M A, Barrett L, Brust D G, Weatherley Barry, Formentini E, Davey R T, Masur H, Polis M A, Neumann And A U, Kottilil S

机构信息

Division of Human Tissues, Office of Cell Therapy and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Rockville, MD, USA.

出版信息

HIV Clin Trials. 2013 Jul-Aug;14(4):149-59. doi: 10.1310/hct1404-149.

DOI:10.1310/hct1404-149
PMID:23924587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5573866/
Abstract

BACKGROUND

Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection.

METHODS

We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks.

RESULTS

Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients.

CONCLUSION

HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.

摘要

背景

人类免疫缺陷病毒(HIV)与乙型肝炎病毒(HBV)合并感染会显著改变HBV的病程。直接作用的抗HBV药物可抑制HBV病毒水平;然而,单一感染和合并感染患者中HBV下降的动力学尚未得到评估。我们研究了基线CD4+T细胞计数在预测合并或未合并HIV感染的慢性HBV患者对阿德福韦(ADV)治疗的HBV反应中的作用。

方法

我们对接受ADV治疗的HIV感染(n = 12)和未感染(n = 5)的慢性HBV患者进行了一项双盲、随机、安慰剂对照研究。5名未感染HIV的患者接受ADV治疗;HIV阳性患者接受ADV或安慰剂治疗,共48周。在48周结束时,所有患者再接受48周的开放标签ADV治疗。在第0、1、3、5、7、10、14和28天以及之后每4周检测HBV、HIV病毒载量、CD4+T细胞计数和安全性实验室指标。

结果

与单一感染患者相比,合并感染患者的HBV下降斜率较低(4周时P = 0.027,24周时P = 0.019,48周时P = 0.045)。使用混合模型分析,我们发现两组在48周时的斜率存在显著差异(P = 0.045)。基线CD4+T细胞计数是所有患者中HBV下降的唯一独立预测因素。

结论

HIV合并感染与对ADV的HBV反应较慢有关。基线CD4+T细胞计数而非IL28B基因型是所有患者中HBV下降的独立预测因素,强调了免疫状态在HBV清除中的作用。

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Hepatitis B virus kinetics under antiviral therapy sheds light on differences in hepatitis B e antigen positive and negative infections.抗病毒治疗下的乙肝病毒动力学揭示了乙肝e抗原阳性和阴性感染的差异。
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