Division of Infectious Diseases, School of Medicine, University of Colorado-AMC, Aurora, CO.
Department of Biostatistics and Bioinformatics, Colorado School of Public Health, Aurora, CO.
J Acquir Immune Defic Syndr. 2020 Dec 1;85(4):483-488. doi: 10.1097/QAI.0000000000002460.
People living with HIV (PLWH) are living longer and developing more non-AIDS comorbidities, which negatively impact antiretroviral therapy (ART) adherence. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a novel pharmacologic measure of cumulative ART adherence that is predictive of viral suppression and future viremia. However, the relationship between non-AIDS comorbidities and this adherence measure is unknown. We aimed to evaluate the association between 3 non-AIDS comorbidities (diabetes mellitus (DM), hypertension, and hyperlipidemia) and TFV-DP in DBS in PLWH.
Blood for TFV-DP in DBS and HIV viral load was prospectively collected from PLWH on tenofovir disoproxil fumarate for up to 3 times over 48 weeks. Non-AIDS comorbidities were recorded. Mixed effect multivariable linear regression models were used to estimate the changes in TFV-DP concentrations in DBS according to the presence of comorbidities and to estimate the percent differences in TFV-DP concentrations between these groups.
A total of 1144 person-visits derived from 523 participants with available concentrations of TFV-DP in DBS were included in this analysis. In univariate analysis, no significant association between non-AIDS comorbidities (categorized as having 0, 1, 2, or 3 comorbidities) and the concentrations of TFV-DP in DBS was observed (P = 0.40). Participants who had DM had 25% lower (95% confidence interval: -36% to -12%; P < 0.001) TFV-DP in DBS than participants without DM after adjusting for age, gender, race, body mass index, estimated glomerular filtration rate, CD4 T-cell count, hematocrit, ART class, patient-level medication regimen complexity index, and 3-month self-reported adherence.
Diabetic PLWH have lower concentrations of TFV-DP in DBS compared with those without DM. Further research is required to identify the clinical implications and biological mechanisms underlying these findings.
感染艾滋病毒（HIV）的患者（PLWH）寿命延长，并出现更多非艾滋病合并症，这对抗逆转录病毒治疗（ART）的依从性产生负面影响。干血斑（DBS）中的替诺福韦二磷酸（TFV-DP）是一种新的药物学指标，可衡量累积 ART 依从性，预测病毒抑制和未来病毒血症。然而，非艾滋病合并症与这种依从性测量之间的关系尚不清楚。我们旨在评估 3 种非艾滋病合并症（糖尿病（DM）、高血压和高血脂）与 PLWH 中 DBS 中 TFV-DP 的关系。
前瞻性收集服用富马酸替诺福韦二吡呋酯的 PLWH 的 DBS 中的 TFV-DP 和 HIV 病毒载量，在 48 周内最多采集 3 次。记录非艾滋病合并症。采用混合效应多变量线性回归模型，根据合并症的存在来估计 DBS 中 TFV-DP 浓度的变化，并估计这些组之间 TFV-DP 浓度的差异百分比。
本分析共纳入了 1144 人次来自 523 名有 DBS 中 TFV-DP 浓度可评估的参与者。在单变量分析中，未观察到非艾滋病合并症（分为无、1 种、2 种或 3 种合并症）与 DBS 中 TFV-DP 浓度之间存在显著关联（P = 0.40）。在调整年龄、性别、种族、体重指数、估计肾小球滤过率、CD4 T 细胞计数、红细胞压积、ART 类别、患者层面药物方案复杂指数和 3 个月自我报告的依从性后，患有 DM 的参与者的 DBS 中 TFV-DP 浓度比没有 DM 的参与者低 25%（95%置信区间：-36%至-12%；P < 0.001）。
与没有 DM 的 PLWH 相比，患有糖尿病的 PLWH 的 DBS 中 TFV-DP 浓度较低。需要进一步研究以确定这些发现的临床意义和生物学机制。
