Castillo-Mancilla Jose R, Searls Kristina, Caraway Patricia, Zheng Jia-Hua, Gardner Edward M, Predhomme Julie, Bushman Lane R, Anderson Peter L, Meditz Amie L
1 Division of Infectious Diseases, School of Medicine, University of Colorado-AMC , Aurora, Colorado.
AIDS Res Hum Retroviruses. 2015 Apr;31(4):428-32. doi: 10.1089/AID.2014.0229. Epub 2014 Nov 20.
Simple and reproducible tools to assess antiretroviral adherence are needed. A level of tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) <1,250 fmol/punch is predicted to identify imperfect adherence. Herein we evaluated TFV-DP in DBS as a measure of adherence among HIV-infected women. DBS and peripheral blood mononuclear cells (PBMCs) were collected twice (∼1 week apart) in 35 well-controlled HIV-infected women [median age 42 years, 14 African American/black (AA)] receiving daily coformulated tenofovir/emtricitabine and either atazanavir/ritonavir (n=20) or raltegravir (n=16). TFV-DP in DBS and PBMCs was quantified by LC-MS/MS. Six-month adherence was measured as average days between monthly pharmacy refills. Data were loge transformed for analysis and presented as median (range); the correlation between continuous variables was analyzed using the Pearson correlation coefficient. The average TFV-DP between the two visits (aTFV-DP) in DBS and PBMCs was 1,874 (706-3,776) fmol/punch and 125 (1-278) fmol/10(6) cells, respectively. AA women had lower levels of aTFV-DP in DBS compared to whites (1,660 vs. 1,970 fmol/punch; p=0.04), with a viremic patient having the lowest drug levels (706 fmol/punch). Days between pharmacy refills were 34 (30-54) vs. 30 (26-40) in women with TFV-DP in DBS <1,250 vs. ≥1,250 fmol/punch (p=0.006). TFV-DP in DBS was negatively correlated with an increasing number of days between refills (r=-0.56, p=0.002). TFV-DP DBS was a reliable and objective measure of adherence in HIV-infected women based on a strong inverse relationship with pharmacy refill adherence.
需要简单且可重复的工具来评估抗逆转录病毒治疗的依从性。干血斑（DBS）中替诺福韦二磷酸（TFV-DP）水平<1250 fmol/打孔被预测可识别依从性不佳。在此，我们评估了DBS中的TFV-DP作为HIV感染女性依从性的一种衡量指标。在35名病情得到良好控制的HIV感染女性（中位年龄42岁，14名非裔美国人/黑人）中，间隔约1周采集两次DBS和外周血单个核细胞（PBMC），这些女性每日接受替诺福韦/恩曲他滨复方制剂治疗，并同时服用阿扎那韦/利托那韦（n = 20）或拉替拉韦（n = 16）。通过液相色谱-串联质谱法（LC-MS/MS）对DBS和PBMC中的TFV-DP进行定量。将六个月的依从性衡量为每月药房取药 refill之间的平均天数。对数据进行自然对数转换以进行分析，并以中位数（范围）表示；使用Pearson相关系数分析连续变量之间的相关性。DBS和PBMC中两次就诊之间的平均TFV-DP（aTFV-DP）分别为1874（706 - 3776）fmol/打孔和125（1 - 278）fmol/10⁶细胞。与白人相比，非裔美国女性DBS中的aTFV-DP水平较低（1660对1970 fmol/打孔；p = 0.04），一名病毒血症患者的药物水平最低（706 fmol/打孔）。DBS中TFV-DP<1250与≥1250 fmol/打孔的女性，药房取药 refill之间的天数分别为34（30 - 54）天和30（26 - 40）天（p = 0.006）。DBS中的TFV-DP与取药 refill间隔天数的增加呈负相关（r = -0.56，p = 0.002）。基于与药房取药 refill依从性的强烈负相关关系，DBS中的TFV-DP是HIV感染女性依从性的可靠且客观的衡量指标。
