Division of Infectious Diseases, School of Medicine, University of Colorado-AMC, Aurora, CO, USA.
Department of Biostatistics and Bioinformatics, Colorado School of Public Health, Aurora, CO, USA.
J Antimicrob Chemother. 2020 Jun 1;75(6):1591-1598. doi: 10.1093/jac/dkaa070.
To determine factors associated with interindividual variability in tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBSs) among persons living with HIV (PLWH).
PLWH who were at least 18 years old and taking tenofovir disoproxil fumarate-containing ART were prospectively recruited and enrolled from a clinical cohort and followed longitudinally (up to three visits over 48 weeks). With log-transformed TFV-DP concentrations in DBSs as the outcome, mixed-model regression analyses were used to assess associations between self-reported 3 month ART adherence, race and other clinical covariates (gender, age, BMI, CD4+ T cell count, estimated glomerular filtration rate, haematocrit, duration on current ART and anchor drug class) on TFV-DP in DBSs.
Five hundred and twenty-seven participants (1150 person-visits) were analysed. Adjusting for race and other clinical covariates, every 10% increase in self-reported 3 month ART adherence was associated with an average TFV-DP concentration increase in DBSs of 28% (95% CI: 24%-32%; P < 0.0001). In the same model, female participants had 20% (95% CI: 3%-40%; P = 0.02) higher TFV-DP concentrations in DBSs, compared with male participants, and every 1 kg/m2 increase in BMI was associated with a decrease in TFV-DP concentration in DBSs by 2% (95% CI: -3% to -1%; P < 0.0001).
Individual patient characteristics were predictive of TFV-DP concentration in DBSs in PLWH receiving tenofovir disoproxil fumarate-based ART. Future research to incorporate these predictors into the interpretation of this ART adherence biomarker, and to establish whether these associations extend to PLWH taking tenofovir alafenamide-containing ART, is needed.
确定与接受富马酸替诺福韦二吡呋酯（TDF）为基础的抗逆转录病毒治疗（ART）的 HIV 感染者（PLWH）的个体间差异相关的因素，以确定在其干血斑（DBS）中检测到的替诺福韦二磷酸（TFV-DP）浓度。
本研究前瞻性招募了至少 18 岁且正在接受 TDF 制剂的 ART 的 PLWH，并从临床队列中招募并进行了纵向随访（最多 48 周内 3 次就诊）。以 DBS 中 TFV-DP 的对数转换浓度为因变量，采用混合模型回归分析评估了自我报告的 3 个月 ART 依从性、种族以及其他临床协变量（性别、年龄、BMI、CD4+T 细胞计数、估计肾小球滤过率、红细胞压积、当前 ART 治疗时间和锚定药物类别）与 DBS 中 TFV-DP 的相关性。
共分析了 527 名参与者（1150 人次就诊）。调整种族和其他临床协变量后，自我报告的 3 个月 ART 依从性每增加 10%，DBS 中 TFV-DP 浓度平均增加 28%（95%CI：24%-32%；P<0.0001）。在相同模型中，与男性参与者相比，女性参与者的 DBS 中 TFV-DP 浓度高 20%（95%CI：3%-40%；P=0.02），而 BMI 每增加 1kg/m2，DBS 中 TFV-DP 浓度则降低 2%（95%CI：-3%至-1%；P<0.0001）。
个体患者特征可预测接受 TDF 制剂为基础的 ART 的 PLWH 中 DBS 中的 TFV-DP 浓度。需要进一步研究，将这些预测因子纳入对该 ART 依从性生物标志物的解释，并确定这些关联是否扩展到接受替诺福韦艾拉酚胺制剂的 PLWH。
