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