Di Yacovo Maria S, Moltó José, Ferrer Elena, Curran Adrian, Else Laura, Gisslén Magnus, Clotet Bonaventura, Tiraboschi Juan M, Niubò Jordi, Vila Antonia, Zetterberg H, Back David, Podzamczer Daniel
Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
J Antimicrob Chemother. 2015 May;70(5):1513-6. doi: 10.1093/jac/dku558. Epub 2015 Jan 20.
The objective of this study was to assess whether a lower dose than the currently used one of darunavir/ritonavir might achieve good CSF concentrations and contribute to inhibition of CNS viral replication.
This was a substudy of a randomized, open, multicentre study (eudraCT 2011-006272-39), comparing the efficacy and safety of 800/100 mg of darunavir/ritonavir (darunavir 800) versus 600/100 mg of darunavir/ritonavir (darunavir 600) once daily plus tenofovir/emtricitabine or abacavir/lamivudine in 100 virologically suppressed patients. Paired blood and CSF samples were obtained. Total plasma darunavir concentrations were determined by HPLC, and CSF concentrations by liquid chromatography-tandem MS. Viral load (VL) was determined in plasma and CSF (limit of detection = 40 copies/mL) by PCR.
Sixteen patients were enrolled. The median (range) of darunavir CSF concentrations in darunavir 600 (n = 8) and darunavir 800 (n = 8) patients was 17.08 (5.79-30.19) and 13.23 (3.47-32.98) ng/mL, respectively (P = 0.916). The median (range) darunavir CSF:plasma ratio was 0.010 (0.005-0.022) in darunavir 600 patients and 0.008 (0.004-0.017) in the darunavir 800 arm (P = 0.370). All 16 patients had a VL < 40 copies/mL in plasma and 14 had a VL < 40 copies/mL in CSF. Of the two patients with detectable CSF VL (280 copies/mL and 159 copies/mL), one was receiving darunavir 600 and the other darunavir 800 plus tenofovir/emtricitabine. Of note, these patients had the lowest CSF darunavir concentrations in their respective groups: 5.79 ng/mL (802 ng/mL in plasma) and 3.47 ng/mL (958 ng/mL in plasma).
Darunavir CSF and plasma concentrations were comparable between the two arms. However, one patient from each group (with the lowest CSF darunavir concentrations in their respective groups) had detectable CSF VL despite undetectable plasma VL.
本研究的目的是评估与目前使用剂量相比，较低剂量的达芦那韦/利托那韦是否能达到良好的脑脊液浓度，并有助于抑制中枢神经系统病毒复制。
这是一项随机、开放、多中心研究（欧盟临床试验注册号2011-006272-39）的子研究，比较了800/100mg达芦那韦/利托那韦（达芦那韦800）与600/100mg达芦那韦/利托那韦（达芦那韦600）每日一次联合替诺福韦/恩曲他滨或阿巴卡韦/拉米夫定在100例病毒学抑制患者中的疗效和安全性。采集配对的血液和脑脊液样本。通过高效液相色谱法测定血浆中达芦那韦的总浓度，通过液相色谱-串联质谱法测定脑脊液浓度。通过聚合酶链反应测定血浆和脑脊液中的病毒载量（检测下限=40拷贝/mL）。
共纳入16例患者。达芦那韦600组（n=8）和达芦那韦800组（n=8）患者的达芦那韦脑脊液浓度中位数（范围）分别为17.08（5.79-30.19）和13.23（3.47-32.98）ng/mL（P=0.916）。达芦那韦600组患者的达芦那韦脑脊液与血浆浓度中位数（范围）之比为0.010（0.005-0.022），达芦那韦800组为0.008（0.004-0.017）（P=0.370）。所有16例患者血浆中的病毒载量均<40拷贝/mL，14例患者脑脊液中的病毒载量<40拷贝/mL。在脑脊液病毒载量可检测到的2例患者（分别为280拷贝/mL和159拷贝/mL）中，1例接受达芦那韦600治疗，另1例接受达芦那韦800联合替诺福韦/恩曲他滨治疗。值得注意的是，这些患者在各自组中的脑脊液达芦那韦浓度最低：分别为5.79ng/mL（血浆中为802ng/mL）和3.47ng/mL（血浆中为958ng/mL）。
两组之间达芦那韦的脑脊液和血浆浓度相当。然而，每组各有1例患者（在各自组中脑脊液达芦那韦浓度最低），尽管血浆病毒载量未检测到，但脑脊液病毒载量可检测到。
