Department of Medicine and Therapeutics, University of Ghana Medical School.
Department of Medicine, Korle-Bu Teaching Hospital, Accra, Ghana.
AIDS. 2024 Mar 1;38(3):351-362. doi: 10.1097/QAD.0000000000003764. Epub 2023 Nov 22.
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.
替诺福韦二磷酸酯（TFV-DP）和拉米夫定三磷酸酯（3TC-TP）在细胞中的浓度与药物依从性和抗病毒活性相关。然而，目前尚缺乏关于 TFV-DP 和 3TC-TP 浓度与 HIV 和乙型肝炎病毒（HBV）抑制之间的同时关系的研究。
我们招募了正在接受包含替诺福韦二吡呋酯（TDF）的抗逆转录病毒疗法（ART）治疗的 HIV/HBV 合并感染患者。采集外周血单核细胞（PBMC）和干血斑（DBS）样本，并使用验证方法定量检测稳态 TFV-DP 和 3TC-TP 浓度。检测患者因素、PBMC 和 DBS 中 TFV-DP 和 3TC-TP 浓度与 HBV 和 HIV 病毒抑制之间的关系。
在中位（范围）时长 6（0.75-15）年的接受 TDF 治疗的 138 名患者中，中位年龄为 43 岁，64%为女性。总的来说，128（92.8%）和 129（93.5%）名患者的 HIV 和 HBV 病毒载量均得到抑制。在 128 名 HIV 得到抑制的患者中，122（95.3%）名患者的 HBV 也得到抑制。自我报告的 ART 依从性、最近改用多替拉韦为基础的 ART、PBMC 和 DBS 中的 TFV-DP 和 3TC-TP 浓度与 HIV RNA 抑制相关，而 HBe 抗原阳性、HIV 抑制和 DBS 中的 TFV-DP 浓度与 HBV DNA 抑制相关（包括 6 名 HBV 未抑制而 HIV 抑制的患者）。
长期接受 TDF/3TC 治疗的 HIV/HBV 合并感染患者具有高度疗效。较高的 TFV-DP 浓度预示着两种病毒的抑制。在接受 TDF/3TC 治疗的患者中持续的 HBV 病毒血症需要进一步研究，但可能代表依从性差，需要采取依从性干预或使用新型抗病毒药物。
