Lombardi Francesca, Belmonti Simone, Borghetti Alberto, Ciccullo Arturo, Baldin Gianmaria, Cauda Roberto, Fabbiani Massimiliano, Di Giambenedetto Simona
Istituto di Clinica Malattie Infettive, Università Cattolica del Sacro Cuore, Roma, Italy.
UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
HIV Res Clin Pract. 2019 Jun;20(3):92-98. doi: 10.1080/25787489.2019.1653512. Epub 2019 Sep 3.
HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients. To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP) and D-dimer. We performed a retrospective case-crossover study on integrase inhibitors-naïve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for ≥48 weeks who switched to 3TC + DTG and maintained this regimen for ≥48 weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48 weeks before (-48 W) and 48 weeks after switch (+48 W). A total of 67 patients were included. Median sCD14 levels were stable from -48 W to BL (from 6.07 to 6.04 log pg/mL, = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84-6.07) log pg/mL at + W48 ( < 0.001). Concurrently, an improvement in lipid profile was observed, even thought it was not correlated to the change in sCD14. The levels of IL-6, CRP, I-FABP and D-dimer remained stable before and after the switch to 3TC + DTG. In virologically suppressed HIV-infected patients on a 3TC + PI/r dual therapy, switching to 3TC + DTG was associated with a significant decline in sCD14. These data suggest reduced monocyte activation following substitution of boosted PI with DTG, which could have important clinical implications.
人类免疫缺陷病毒（HIV）引起的全身免疫激活和炎症与病毒学抑制患者的发病率和死亡率相关。为了评估从拉米夫定（3TC）加ritonavir增强蛋白酶抑制剂（PI/r）的双药方案转换为3TC加度鲁特韦（DTG）治疗对单核细胞激活标志物可溶性CD14（sCD14）以及其他炎症生物标志物白细胞介素-6（IL-6）、C反应蛋白（CRP）、肠脂肪酸结合蛋白（I-FABP）和D-二聚体的影响。我们对初治的病毒学抑制患者进行了一项回顾性病例交叉研究，这些患者在接受3TC + PI/r双药维持治疗≥48周后转换为3TC + DTG并维持该方案≥48周。通过酶联免疫吸附测定（ELISA）法在三个时间点对储存样本检测生物标志物血浆水平：转换时（基线）、转换前48周（-48W）和转换后48周（+48W）。共纳入67例患者。sCD14水平中位数从-48W到基线时稳定（从6.07降至6.04 log pg/mL，P = 0.235），但转换后出现统计学显著下降：从基线时的6.04（四分位间距5.92 - 6.12）降至+48W时的5.95（四分位间距5.84 - 6.07）log pg/mL（P < 0.001）。同时，观察到血脂谱有所改善，尽管其与sCD14的变化无关。转换为3TC + DTG前后，IL-6、CRP、I-FABP和D-二聚体水平保持稳定。在接受3TC + PI/r双药治疗的病毒学抑制的HIV感染患者中，转换为3TC + DTG与sCD14显著下降相关。这些数据表明用DTG替代增强型PI后单核细胞激活减少，这可能具有重要的临床意义。
