St. Stephen's AIDS Trust-Chelsea and Westminster Hospital, London.
Imperial College, London.
Clin Infect Dis. 2019 Jan 1;68(1):87-95. doi: 10.1093/cid/ciy426.
Demographic data show an increasingly aging human immunodeficiency virus (HIV) population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older people living with HIV (PLWH). We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50 mg once daily in PLWH aged 60 and older. Additionally, to address calls for prospective neuropsychiatric toxicodynamic data, we evaluated changes in sleep quality and cognitive functioning in this population after switching to abacavir (ABC)/lamivudine (3TC)/DTG over 6 months.
PLWH ≥60 years with HIV-viral load <50 copies/mL on any non-DTG-based antiretroviral combination were switched to ABC/3TC/DTG. On day 28, 24-hour PK sampling was undertaken. Steady-state PK parameters were compared to a published historical control population aged ≤50 years. We administered 6 validated sleep questionnaires and neurocognitive (Cogstate) testing pre-switch and over 180 days.
In total, 43 participants enrolled, and 40 completed the PK phase. Overall, 5 discontinued (2 due to sleep-related adverse events, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients ≥60 years old versus controls (geometric mean 4246 ng/mL versus 3402 ng/mL, P = .005). In those who completed day 180 (n = 38), sleep impairment (Pittsburgh Sleep Quality Index) was marginally higher at day 28 (P = .02), but not at days 90 or 180. Insomnia, daytime functioning, and fatigue test scores did not change statistically over time.
DTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH.
人口统计学数据显示，全球范围内人类免疫缺陷病毒（HIV）感染者群体日益老龄化。最近，人们对多替拉韦相关神经精神毒性的担忧日益加剧，尤其是在感染 HIV 的老年人（PLWH）中。我们描述了年龄在 60 岁及以上的 PLWH 中每日一次服用 50 毫克多替拉韦的药代动力学（PK）。此外，为了满足对前瞻性神经精神毒性动力学数据的需求，我们在 6 个月内将这些患者转换为阿巴卡韦（ABC）/拉米夫定（3TC）/多替拉韦后，评估了他们的睡眠质量和认知功能变化。
HIV 载量<50 拷贝/mL 的任何非多替拉韦为基础的抗逆转录病毒联合治疗方案中的 PLWH 年龄≥60 岁，转换为 ABC/3TC/DTG。在第 28 天进行 24 小时 PK 采样。将稳态 PK 参数与年龄≤50 岁的已发表历史对照人群进行比较。在转换前和 180 天内，我们使用 6 种经过验证的睡眠问卷和神经认知（Cogstate）测试进行了评估。
共有 43 名患者入组，40 名患者完成了 PK 阶段。总的来说，5 名患者停药（2 名因睡眠相关不良反应，4.6%）。年龄≥60 岁的患者与对照组相比，多替拉韦最大浓度（Cmax）显著升高（几何均数 4246ng/mL 比 3402ng/mL，P=0.005）。在完成第 180 天的 38 名患者中，第 28 天睡眠障碍（匹兹堡睡眠质量指数）略有升高（P=0.02），但在第 90 天和第 180 天没有统计学上的变化。失眠、白天功能和疲劳测试评分在整个时间内没有统计学上的变化。
年龄较大的 PLWH 中多替拉韦的 Cmax 显著升高。我们的数据为临床医生提供了在老年 PLWH 中开具多替拉韦处方的安全性关键信息。
