Yilmaz Aylin, De Nicolò Amedeo, D'Avolio Antonio, Gisslén Magnus
Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Sahlgrenska Academy, Sweden; Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, Italy.
Antiviral Res. 2025 Sep;241:106243. doi: 10.1016/j.antiviral.2025.106243. Epub 2025 Jul 23.
Our aim was to determine cerebrospinal fluid (CSF) and plasma concentrations of cabotegravir and rilpivirine (CAB/RPV) when administered as long-acting (LA) intramuscular injections every four (Q4W) or eight (Q8W) weeks, and to study the effect on viral suppression and CSF biomarkers of inflammation and neuronal injury. We included six adults with HIV receiving LA CAB/RPV Q4W or Q8W. CSF and plasma concentrations of CAB/RPV (15 samples) were analyzed by UHPLC-MS/MS. We also measured CSF and plasma HIV RNA, CSF and serum neopterin, CSF and serum β2-microglubulin, IgG index, albumin ratio, and CSF NfL. Median (range) total plasma cabotegravir concentrations were 1375 (963-2422) ng/mL, and in CSF 3.48 (1.47-7.60 ng/mL). For rilpivirine, concentrations were 93 (40-157) ng/mL and 1.21 (0.55-1.67) ng/mL, respectively. All participants hade CSF and plasma HIV RNA <20 copies/mL on every occasion. There were no significant changes in any of the CSF biomarkers in participants after switching to LA CAB/RPV. The combination of LA CAB/RPV can achieve therapeutic CSF concentrations throughout the dosing intervals and may suppress HIV replication in the CNS. No significant changes in CSF biomarkers of inflammation or neuronal injury were observed, indicating a neutral CNS effect.
我们的目标是确定每四周（Q4W）或每八周（Q8W）进行长效（LA）肌肉注射时，卡博特韦和利匹韦林（CAB/RPV）的脑脊液（CSF）和血浆浓度，并研究其对病毒抑制以及炎症和神经元损伤的脑脊液生物标志物的影响。我们纳入了六名接受Q4W或Q8W长效CAB/RPV治疗的HIV成人患者。通过超高效液相色谱-串联质谱法（UHPLC-MS/MS）分析CAB/RPV的脑脊液和血浆浓度（15个样本）。我们还测量了脑脊液和血浆中的HIV RNA、脑脊液和血清中的新蝶呤、脑脊液和血清中的β2-微球蛋白、IgG指数、白蛋白比率以及脑脊液中的神经丝轻链（NfL）。血浆中卡博特韦的总浓度中位数（范围）为1375（963 - 2422）ng/mL，脑脊液中为3.48（1.47 - 7.60）ng/mL。利匹韦林的浓度分别为93（40 - 157）ng/mL和1.21（0.55 - 1.67）ng/mL。所有参与者每次脑脊液和血浆中的HIV RNA均<20拷贝/mL。转换为长效CAB/RPV治疗后，参与者的任何脑脊液生物标志物均无显著变化。长效CAB/RPV组合在整个给药间隔期内均可达到治疗性脑脊液浓度，并可能抑制中枢神经系统中的HIV复制。未观察到炎症或神经元损伤的脑脊液生物标志物有显著变化，表明对中枢神经系统无不良影响。
