PDF(Pubmed)
Abstract：
Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression.
Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined.
Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression).
Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.
Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined.
Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression).
Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.
摘要：
目的：细胞中替诺福韦二磷酸（TFV-DP）和拉米夫定三磷酸（3TC-TP）的浓度与药物依从性和抗病毒活性相关。然而,研究尚未描述TFV-DP和3TC-TP浓度与人类免疫缺陷病毒（HIV）和乙型肝炎病毒（HBV）抑制之间的同时关系。
方法：纳入含有富马酸替诺福韦酯（TDF）的抗逆转录病毒疗法（ART）的HIV/HBV合并感染患者。收集外周血单核细胞（PBMC）和干血斑（DBS）样品，并使用经验证的方法定量稳态TFV-DP和3TC-TP浓度。患者因素之间的关系，TFV-DP和3TC-TP浓度在PBMC和DBS与HBV和HIV病毒抑制进行了检查。
结果：在包含TDF的ART的138名参与者中，中位持续时间（范围）为6（0.75-15）年，中位年龄为43岁,64%为女性.总的来说,128（92.8％）和129（93.5％）抑制了HIV和HBV病毒载量，分别。在128名HIV受到抑制的参与者中，122（95.3%）抑制HBV。自我报告ART依从性，最近更改了基于dolutegravir的ART，PBMC和DBS中的TFV-DP和3TC-TP浓度与HIVRNA抑制有关，而HBe抗原阳性，DBS中的HIV抑制和TFV-DP浓度与HBVDNA抑制（包括6名HBV非抑制和HIV抑制的人）相关。
结论：长期TDF/3TC联合ART在HIV/HBV合并感染的个体中非常有效。较高的TFV-DP浓度预示了两种病毒的抑制。持续的HBV病毒血症在TDF/3TC-containgART需要额外的研究，但可能代表依从性差,需要依从性干预或新型抗病毒药物.
方法：纳入含有富马酸替诺福韦酯（TDF）的抗逆转录病毒疗法（ART）的HIV/HBV合并感染患者。收集外周血单核细胞（PBMC）和干血斑（DBS）样品，并使用经验证的方法定量稳态TFV-DP和3TC-TP浓度。患者因素之间的关系，TFV-DP和3TC-TP浓度在PBMC和DBS与HBV和HIV病毒抑制进行了检查。
结果：在包含TDF的ART的138名参与者中，中位持续时间（范围）为6（0.75-15）年，中位年龄为43岁,64%为女性.总的来说,128（92.8％）和129（93.5％）抑制了HIV和HBV病毒载量，分别。在128名HIV受到抑制的参与者中，122（95.3%）抑制HBV。自我报告ART依从性，最近更改了基于dolutegravir的ART，PBMC和DBS中的TFV-DP和3TC-TP浓度与HIVRNA抑制有关，而HBe抗原阳性，DBS中的HIV抑制和TFV-DP浓度与HBVDNA抑制（包括6名HBV非抑制和HIV抑制的人）相关。
结论：长期TDF/3TC联合ART在HIV/HBV合并感染的个体中非常有效。较高的TFV-DP浓度预示了两种病毒的抑制。持续的HBV病毒血症在TDF/3TC-containgART需要额外的研究，但可能代表依从性差,需要依从性干预或新型抗病毒药物.
