University at Buffalo, Buffalo, New York, USA.
University of California, San Diego, La Jolla, California, USA.
Clin Infect Dis. 2020 Aug 14;71(4):982-988. doi: 10.1093/cid/ciz926.
Tenofovir alafenamide fumarate (TAF) co-formulated with elvitegravir (EVG; E), cobicistat (C), and emtricitabine (F), a recommended antiretroviral regimen, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF) as well as neurocognitive (NC) performance change in participants switching from E/C/F/tenofovir disoproxil fumarate (TDF) to E/C/F/TAF.
This was a 24-week, single-arm, open-label study in treatment-experienced adults living with human immunodeficiency virus (HIV). Nine participants switched from E/C/F/TDF (150/150/200/300 mg once daily) to E/C/F/TAF (150/150/200/10 mg once daily) at week 12. CSF and total plasma concentrations of EVG, TDF, TAF, tenofovir (TFV), and HIV RNA levels were measured at baseline and week 24. NC performance was estimated by the Montreal Cognitive Assessment.
EVG concentrations in CSF and the CSF:plasma ratio remained stable (P = .203) over time. Following the switch, TFV concentrations in CSF and plasma declined (P = .004), although the TFV CSF:plasma ratio increased (P = .004). At week 24, median TAF plasma concentration was 11.05 ng/mL (range, 2.84-147.1 ng/mL) 2 hours postdose but was below assay sensitivity 6 hours after dosing. TAF was below assay sensitivity in all CSF specimens. HIV RNA was ≤40 copies/mL in all CSF and plasma specimens. Three participants (33%) had NC impairment at baseline and 2 (22%) remained impaired at week 24.
Switch to E/C/F/TAF was associated with reductions in TFV concentrations in CSF but stable EVG concentrations that exceeded the 50% inhibitory concentration for wild-type HIV, suggesting that EVG achieves therapeutic concentrations in the central nervous system. No virologic failure or significant NC changes were detected following the switch.
NCT02251236.
富马酸替诺福韦艾拉酚胺（TAF）与艾维雷格（EVG）、考比司他（C）和恩曲他滨（F）联合制剂，是一种推荐的抗逆转录病毒方案，其在脑脊液（CSF）中的分布和抗病毒活性以及从 E/C/F/替诺福韦二吡呋酯（TDF）转换为 E/C/F/TAF 的参与者的神经认知（NC）性能变化已进行了评估。
这是一项 24 周、单臂、开放性标签的研究，纳入了接受过治疗的人类免疫缺陷病毒（HIV）感染者。9 名参与者在第 12 周时从 E/C/F/TDF（150/150/200/300mg 每日一次）转换为 E/C/F/TAF（150/150/200/10mg 每日一次）。在基线和第 24 周时，测量了 EVG、TDF、TAF、替诺福韦（TFV）和 HIV RNA 水平的 CSF 和总血浆浓度。通过蒙特利尔认知评估来评估 NC 表现。
EVG 在 CSF 中的浓度和 CSF：血浆比值在整个研究过程中保持稳定（P=0.203）。转换后，CSF 和血浆中的 TFV 浓度下降（P=0.004），尽管 TFV 的 CSF：血浆比值增加（P=0.004）。第 24 周时，TAF 血浆浓度的中位数为 11.05ng/mL（范围，2.84-147.1ng/mL），在给药后 2 小时，但在给药后 6 小时时低于检测灵敏度。所有 CSF 标本中均未检测到 TAF。所有 CSF 和血浆标本中 HIV RNA 均＜40 拷贝/mL。3 名参与者（33%）在基线时有 NC 损伤，2 名（22%）在第 24 周时仍有损伤。
转换为 E/C/F/TAF 与 CSF 中 TFV 浓度降低有关，但 EVG 浓度稳定，超过野生型 HIV 的 50%抑制浓度，表明 EVG 在中枢神经系统中达到了治疗浓度。转换后未检测到病毒学失败或显著的 NC 变化。
NCT02251236。
