Clinic of Infectious Diseases, "San Gerardo" Hospital, ASST Monza, University Milano-Bicocca Monza, Italy.
Infectious Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, Milano, Italy.
J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):290-294. doi: 10.1097/QAI.0000000000002331.
This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated.
Prospective, multicenter, single-country, noninterventional cohort study.
This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA <50 copies/mL since at least 6 months. The primary endpoint, defined as HIV-1 RNA <50 copies/mL, was measured at 48 ± 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response algorithm. Biochemical parameters, including DRV trough samples, were collected as per clinical practice and measured using high-performance liquid chromatography.
Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA <50 copies/mL at 48 weeks; using the time to loss of virological response algorithm, 82.7% maintained virological suppression. Virological failure was observed in 6 patients (1.8%). Adverse event-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130 to 113.5 mg/dL, P = 0.0254) and high-density lipoprotein cholesterol (48 to 49 mg/dL, P < 0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439) ng/mL, higher in women than in men (4221 vs. 2634 ng/mL, P = 0.046).
In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of virological failure and adverse events due to its high tolerability and improvement in triglycerides.
本研究旨在评估对已接受利托那韦增强的蛋白酶抑制剂（PI/r）方案治疗至少 12 个月且病毒学抑制至少 6 个月的 HIV 阳性患者，转换为达芦那韦/考比司他（DRV/c）方案的疗效和耐受性。同时还对 DRV 谷浓度进行了研究。
前瞻性、多中心、单国籍、非干预性队列研究。
本研究纳入了正在接受 PI/r 方案治疗至少 12 个月且血浆 HIV-1 RNA 检测不到（<50 拷贝/ml）至少 6 个月的患者。主要终点定义为从基线开始的 48±6 周时 HIV-1 RNA <50 拷贝/ml，使用病毒学失败时间算法进行了二次分析。按照临床实践收集了包括 DRV 谷浓度样本在内的生化参数，并使用高效液相色谱法进行了测量。
336 名患者中，282 名完成了研究：48 周时，70.8%的患者 HIV-1 RNA <50 拷贝/ml；使用病毒学失败时间算法，82.7%的患者维持了病毒学抑制。6 例（1.8%）患者出现病毒学失败。与不良事件相关的停药率为 4.5%。48 周后，我们发现甘油三酯（中位数，从 130 降至 113.5mg/dl，P=0.0254）和高密度脂蛋白胆固醇（从 48 升至 49mg/dl，P<0.0001）均显著改善，但其他生物标志物无变化。56 名受试者的 DRV 谷浓度中位数为 2862.5（1469.5-4439）ng/ml，女性高于男性（4221 与 2634ng/ml，P=0.046）。
在 HIV-1 阳性、病毒学抑制稳定的患者中，由于 DRV/c 方案具有较高的耐受性和改善甘油三酯的作用，因此转换为 DRV/c 方案治疗的患者病毒学失败率和不良事件发生率较低，具有明显的益处。
