Kawashima Akira, Trung Hieu Tran, Watanabe Koji, Takano Misao, Deguchi Yoshimi, Kinoshita Mai, Uemura Haruka, Yanagawa Yasuaki, Gatanaga Hiroyuki, Kikuchi Yoshimi, Oka Shinichi, Tsuchiya Kiyoto
AIDS Clinical Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan.
The Joint Research Center for Human Retrovirus Infection Kumamoto University Campus, Kumamoto City, Kumamoto, Japan.
Microbiol Spectr. 2023 Feb 21;11(2):e0507922. doi: 10.1128/spectrum.05079-22.
Bictegravir (BIC) is an integrase strand transfer inhibitor widely used in the treatment of HIV-1. Although its potency and safety have been demonstrated in older patients, pharmacokinetics (PK) data remain limited in this patient population. Ten male patients aged 50 years or older with suppressed HIV RNA on other antiretroviral regimens were switched to a single-tablet regimen of BIC, emtricitabine, and tenofovir alafenamide (BIC+FTC+TAF). Four weeks later, plasma samples were collected at 9 time points for PK. Safety and efficacy were also assessed up to 48 weeks. The median age (range) of patients was 57.5 (50 to 75) years. Although 8 (80%) had lifestyle diseases requiring treatment, no participants had renal or liver failure. Nine (90%) were receiving dolutegravir-containing antiretroviral regimens at entry. The trough concentration of BIC was 2,324 (1,438 to 3,756) (geometric mean [95% confidence interval]) ng/mL, which was markedly above the 95% inhibitory concentration of the drug (162 ng/mL). All PK parameters, including area under the blood concentration-time curve and clearance, were similar to those in young HIV-negative Japanese participants in a previous study. No correlations between age and any PK parameters were observed in our study population. No participant experienced virological failure. Body weight, transaminase, renal function, lipid profiles, and bone mineral density were unchanged. Interestingly, urinary albumin was decreased after switching. PK of BIC was not affected by age, indicating that BIC+FTC+TAF may be safely used in older patients. BIC is a potent integrase strand transfer inhibitor (INSTI), widely used for the treatment of HIV-1 as part of a once-daily single-tablet regimen that includes emtricitabine and tenofovir alafenamide (BIC+FTC+TAF). Although the safety and efficacy of BIC+FTC+TAF have been confirmed in older patients with HIV-1, PK data in this patient population remain limited. Dolutegravir (DTG), an antiretroviral medication with a similar structural formula to BIC, causes neuropsychiatric adverse events. PK data for DTG have shown a higher maximum concentration () among older patients than younger patients and are related to a higher frequency of adverse events. In the present study, we prospectively collected BIC PK data from 10 older HIV-1-infected patients and showed that PK of BIC are not affected by age. Our results support the safe use of this treatment regimen among older patients with HIV-1.
比克替拉韦（BIC）是一种整合酶链转移抑制剂，广泛用于治疗HIV-1。尽管其有效性和安全性已在老年患者中得到证实，但该患者群体的药代动力学（PK）数据仍然有限。10名年龄在50岁及以上、在其他抗逆转录病毒治疗方案下HIV RNA得到抑制的男性患者改用BIC、恩曲他滨和替诺福韦艾拉酚胺的单片治疗方案（BIC+FTC+TAF）。四周后，在9个时间点采集血浆样本进行PK检测。还评估了长达48周的安全性和有效性。患者的中位年龄（范围）为57.5（50至75）岁。虽然8名（80%）患者患有需要治疗的生活方式疾病，但没有参与者出现肾衰竭或肝功能衰竭。9名（90%）患者在入组时接受含多替拉韦的抗逆转录病毒治疗方案。BIC的谷浓度为2324（1438至3756）（几何均值[95%置信区间]）ng/mL，明显高于该药物的95%抑制浓度（162 ng/mL）。所有PK参数，包括血药浓度-时间曲线下面积和清除率，均与先前一项研究中年轻的HIV阴性日本参与者相似。在我们的研究人群中，未观察到年龄与任何PK参数之间存在相关性。没有参与者出现病毒学失败。体重、转氨酶、肾功能、血脂谱和骨密度均未改变。有趣的是，换药后尿白蛋白降低。BIC的PK不受年龄影响，这表明BIC+FTC+TAF可安全用于老年患者。BIC是一种强效整合酶链转移抑制剂（INSTI），作为一种每日一次的单片治疗方案的一部分广泛用于治疗HIV-1，该方案包括恩曲他滨和替诺福韦艾拉酚胺（BIC+FTC+TAF）。尽管BIC+FTC+TAF在老年HIV-1患者中的安全性和有效性已得到证实，但该患者群体的PK数据仍然有限。多替拉韦（DTG）是一种与BIC结构相似的抗逆转录病毒药物，会引起神经精神方面的不良事件。DTG的PK数据显示，老年患者的最高浓度（）高于年轻患者，且与更高频率的不良事件相关。在本研究中，我们前瞻性地收集了10名老年HIV-1感染患者的BIC PK数据，并表明BIC的PK不受年龄影响。我们的结果支持在老年HIV-1患者中安全使用该治疗方案。
