Calcagno A, Pagani N, Ariaudo A, Arduino G, Carcieri C, D'Avolio A, Marinaro L, Tettoni M C, Trentini L, Di Perri G, Bonora S
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
J Antimicrob Chemother. 2017 Jun 1;72(6):1741-1744. doi: 10.1093/jac/dkx052.
Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure.
A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards.
The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P < 0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P = 0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P < 0.001), genotypic susceptibility score ≤2 ( P = 0.001), lower nadir CD4 cell count ( P = 0.003) and not being in the adherent group ( P = 0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks.
The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions.
在部分HIV阳性患者中开展抗逆转录病毒药物的治疗药物监测（TDM）。本研究旨在估算利托那韦及增效蛋白酶抑制剂（PI）血浆浓度未检出的发生率，并评估其与48周病毒学失败风险之间的关联。
开展了一项TDM登记研究及一项回顾性随访研究。通过经验证的方法测定血浆浓度。根据PI及利托那韦浓度，将患者分为依从、部分不依从或不依从。48周后评估病毒学转归。
TDM登记研究纳入了从723例患者（68.1%为男性，中位年龄43.5岁）采集的2468份样本。分别有87份样本（3.5%，74例患者）及68份样本（2.8%，52例患者）属于部分不依从组及不依从组；在部分不依从组中，接受阿扎那韦/利托那韦治疗的患者更多（7.9%），而接受达芦那韦/利托那韦治疗的患者（每日2次为2%，每日1次为1.9%）及洛匹那韦/利托那韦治疗的患者（1.5%；P＜0.001）较少。随访研究纳入了290例患者（64.1%为男性，中位年龄40岁）。依从组患者实现病毒学抑制的几率更高[81.9%（167/204）]，而部分不依从组及不依从组分别为[71.7%（33/46）及53.1%（17/32）；P = 0.001]。基于多变量分析，基线HIV RNA>50拷贝/mL（P＜0.001）、基因型易感性评分≤2（P = 0.001）、更低的最低点CD4细胞计数（P = 0.003）以及不属于依从组（P = 0.029）是48周时HIV RNA>50拷贝/mL的独立预测因素。
PI及利托那韦血浆水平的测定可发现治疗依从性不佳的情况；TDM可能是识别需要促进依从性干预措施的患者的有用工具。
