A Randomized Non-Inferiority Trial to Compare the Efficacy of Switching From Protease-Inhibitor Based Second-Line Therapy to Bictegravir-Tenofovir Alafenamide-Emtricitabine in Virologically Suppressed Adults in Haiti
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 386
- 试验地点
- 1
- 主要终点
- Virologic failure - 200 Copies/mL cut-off
研究概览
简要总结
This randomized trial compares the efficacy of switching to a fixed-dose combination of B/F/TAF versus continuing a boosted protease inhibitor (bPI) regimen in HIV-1 infected participants who are virologically suppressed (HIV-1 RNA <200 copies) on a second-line bPI regimen. Half of participants will receive B/F/TAF and half will continue a bPI regimen. The hypothesize is that B/F/TAF will have efficacy that is non-inferior to the boosted PI regimen.
详细描述
The second generation integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) and bictegravir (BIC) are widely prescribed for the treatment of HIV, due to their favorable tolerability and toxicity profile, durable efficacy, and high barrier to resistance. However, there are limited data to guide the management of patients who are already virally suppressed on a second-line bPI regimen.
Though bPIs have a high barrier to resistance and durable virologic efficacy, they have several important drug-drug interactions, are associated with unfavorable long-term metabolic effects, and may be poorly tolerated. For these reasons, a second-generation INSTI would be preferable to a boosted PI regimen, as long INSTIs are demonstrated to have non-inferior efficacy for patients who are already suppressed on a second-line bPI regimen.
In the proposed study, the efficacy of continuing the bPI regimen will be compared to switching to B/F/TAF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open label study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The ability and willingness to give informed consent.
- •Age ≥18 years
- •History of meeting WHO criteria for immunologic or virologic failure after receipt of a first-line treatment regimen for ≥6 months
- •Currently receiving a second-line ART regimen including either ATVr or LPVr + 2 NRTIs for ≥6 months
- •At least one HIV-1 RNA <200 copies/mL within 12 months prior to enrollment, and no HIV-1 RNA of at least 200 copies/mL during this period.
- •Plasma HIV-1 RNA <200 copies/mL at Screening Visit.
- •eGFR ≥ 50 mL/min according to the MDRD study equation for creatinine clearance
- •Hepatic transaminases (AST and ALT) </=5X upper limit of normal (ULN)
- •No active TB
- •Women of childbearing age must agree to take reliable contraception
排除标准
- •Active World Health Organization Stage 3 or 4 condition
- •Treatment with an INSTI in the past
- •Gap in care of at least one month in the prior six months
- •Current alcohol or substance use judged by investigator to potentially interfere with participant study compliance
- •History of poor adherence, that in the opinion of the investigator, would potentially interfere with study compliance
- •Pregnant or breastfeeding at screening visit
- •Planning to transfer care
研究组 & 干预措施
Boosted PI Group
Continuation of the same second-line regimen taken prior to entry:
This includes either Lopinavir/ritonavir (LPVr) 400 mg/100 mg BID or Atazanavir/ritonavir (ATV/r) 300 mg/100 mg QD
plus 2 nucleoside reverse transcriptase inhibitors (NRTIs).
干预措施: Continuation of boosted PI (Drug)
B/F/TAF Group
Combination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.
干预措施: B/F/TAF (Drug)
结局指标
主要结局
Virologic failure - 200 Copies/mL cut-off
时间窗: Week 48
Proportion of participants with HIV-1 RNA at least 200 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm
次要结局
- Virologic failure - 50 Copies/mL cut-off(Week 48)
- Virologic failure - 1000 Copies/mL cut-off(Week 48)
- Tolerability as measured by discontinuing medication(Entry to 48 weeks)
- Adverse events(Entry to 48 weeks)
- Change in cholesterol(Entry to 48 weeks)
- Change in weight(Entry to 48 weeks)
- Change in body mass index(Entry to 48 weeks)
- Weight gain of 10% or greater(Entry to 48 weeks)
- Change in waist circumference(Entry to 48 weeks)
- Waist to hip ratio(Entry to 48 weeks)
- Adherence(Entry to 48 weeks)