Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton, BN1 9PX, UK.
Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
BMC Infect Dis. 2020 Jul 20;20(1):524. doi: 10.1186/s12879-020-05240-y.
Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC).
METHODS/DESIGN: A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures.
We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations.
ISRCTN 44453201 , registered 19 June 2019 and EudraCT 2018-004732-30.
目前推荐的强化蛋白酶抑制剂（bPI）方案可能会增加心血管疾病或慢性肾脏疾病的风险；此外，强化方案尤其与药物相互作用有关。由于心血管疾病和肾脏疾病以及多种药物治疗在感染 HIV 的老年人中很常见，因此需要替代有效的方案。基于 bPI 的方案通常是治疗有治疗前或治疗后耐药的个体的首选方案，但合理的是，对于那些对目前 bPI 方案病毒学抑制但耐药性选择的 HIV 阳性个体，在改用比替拉韦、恩曲他滨和替诺福韦艾拉酚胺（B/F/TAF）固定剂量复方（FDC）时，可以保持病毒学疗效。
方法/设计：这是一项由研究者发起的、多中心、开放性、随机、双臂的 IV 期研究，旨在评估在携带耐药突变的初治或治疗后获得抑制的 HIV-1 感染成人中，从 bPI 方案转换为 B/F/TAF 单一片剂方案的安全性和疗效。符合条件的个体将继续接受 bPI 方案或转换为 B/F/TAF FDC。24 周后，bPI 组的所有参与者将转换为 B/F/TAF，并随访 24 周，所有参与者将随访 48 周。主要疗效终点是使用纯病毒学应答时第 24 周时 HIV-1 RNA<50 拷贝/ml 的参与者比例，次要疗效终点是第 48 周时 HIV-1 RNA<50 拷贝/ml 的参与者比例。其他次要结局包括在病毒学失败时药物耐药性的组间比较、安全性和耐受性以及患者报告的结局测量。
我们旨在为在基于 bPI 的方案下病毒学抑制且携带选择耐药突变的患者转换为 B/F/TAF 提供初步疗效证据。
ISRCTN44453201，于 2019 年 6 月 19 日注册，EudraCT 2018-004732-30。
