Ferretti Francesca, Bigoloni Alba, Passeri Laura, Galli Laura, Longo Valeria, Gerevini Simonetta, Spagnuolo Vincenzo, Gisslen Magnus, Zetterberg Henrik, Fuchs Dietmar, Cattaneo Dario, Caramatti Giada, Lazzarin Adriano, Cinque Paola, Castagna Antonella
Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute Neuroradiology Unit, Head and Neck Department, IRCCS San Raffaele Scientific Institute, Milan, Italy Department of Infectious Diseases, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy.
Medicine (Baltimore). 2016 Jul;95(28):e4144. doi: 10.1097/MD.0000000000004144.
Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy.
This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible.We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate.
HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms.
CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.
在利托那韦增强的蛋白酶抑制剂单药治疗中，脑脊液（CSF）病毒逃逸是一个令人担忧的问题。目的是评估长期成功接受阿扎那韦/利托那韦（ATV/r）单药治疗的患者脑脊液中的HIV-RNA、免疫激活和神经退行性变的生物标志物以及阿扎那韦浓度。
这是一项多中心、随机、开放标签、非劣效性试验的子研究，该试验为每日一次阿扎那韦/利托那韦单药治疗（NCT01511809），将持续使用ATV/r联合2种核苷类逆转录酶抑制剂（NRTIs）方案与简化的ATV/r单药治疗进行比较。至少96个研究周后血浆HIV-RNA < 50拷贝/mL的患者符合条件。我们通过酶联免疫吸附测定评估HIV-RNA、可溶性（s）CD14、sCD163、CCL2、CXCL10、白细胞介素-6和YKL40；通过免疫测定评估新蝶呤、色氨酸、犬尿氨酸和神经丝；通过液相色谱-质谱法测定配对血浆和脑脊液样本中的阿扎那韦浓度。根据情况，变量采用Wilcoxon秩和检验或Fisher精确检验进行比较。
在接受ATV/r单药治疗的11例患者中的1例（114拷贝/mL）脑脊液中检测到HIV-RNA，该患者无神经症状，随后成功重新强化使用其先前的2种NRTIs，而在接受ATV/r + 2NRTIs治疗的12例患者中均未检测到。两组之间的脑脊液生物标志物和阿扎那韦浓度没有差异。
长期接受ATV/r单药治疗的患者中脑脊液逃逸不常见，通过重新强化治疗可得到控制。
