Switch From Stable cART Containing ABA/3TC or TAF/FTC Plus Dolutegravir or Bictegravir to TDF/3TC/Doravirine in People Living With HIV: Impact on Lipids, Body Composition, Insulin Sensitivity, Neuroendocrine Function and Inflammation Markers
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 19
- 试验地点
- 4
- 主要终点
- To quantify the effect on lipid profile
研究概览
简要总结
This is an open label, randomised, two-arm switch study over 48 weeks in which virally suppressed participants on a stable combined ART regimen will be randomised (1:1) to an immediate switch to 3TC/TDF/DOR (immediate switch arm, N=30) for the duration of the 48-week study, or to maintaining their current cART followed by a switch to 3TC/TDF/DOR from week 24-48 (delayed switch arm, N=30). Participants will be monitored for the length of the study (48 weeks) plus a 30-day follow-up period.
If patients withdraw or are withdrawn from the study treatment prematurely, an early termination visit (ETV) should occur within 30 days post withdrawal.
The hypothesis of the study is that a switch to Delstrigo, which is a combination of tenofovir disoproxil, lamivudine and doravirine (TDF/3TC/DOR) has a favourable impact on lipid metabolism, glucose, weight, body composition and hepatic steatosis.
详细描述
Open-label, 2 arm, multi-centre, non-inferiority switch study.
Sample size: 60 participants
Participant population: HIV-1 infected patients on stable and suppressive triple cART.
IMP: Delstrigo (300 mg of tenofovir disoproxil fumarate equivalent to 245 mg of tenofovir disoproxil, 300 mg of lamivudine and 100 mg of doravirine
- TDF/3TC/DOR)
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
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
- •HIV-1 infected, 18 years or older
- •On stable & suppressive triple cART containing ABA/3TC or TAF/FTC plus dolutegravir or bictegravir for at least 6 months
- •No evidence of resistance to TDF, 3TC, or DOR
- •No laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators
- •Women who are of childbearing potential and sexually active need to use the hormonal contraceptive methods, associated with inhibition of ovulation, listed in the protocol:
- •Depot injection
- •Intra-uterine device or system
- •Oral hormonal contraception A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
- •Men who are sexually active and have partners who are women of childbearing potential must be using an adequate method of contraception to avoid pregnancy (male condom or sterilisation confirmed prior to the subject's entry into the study)
排除标准
- •History of virological failure on an NNRTI in absence of a post-failure genotypic resistance test proving absence of resistance to DOR
- •Concomitant medication contra-indicated with TDF, FTC or DOR
- •Haemoglobin <9 g/dL
- •Platelets <80,000/mm3
- •Creatinine clearance <50 mL/min
- •AST or ALT ≥5N
- •Acute Hepatitis A infection.
- •Concomitant DAA for anti-HCV therapy
- •Known acute or chronic viral hepatitis B or C.
- •o Individuals with positive anti-HCV results, but with HCV RNA not detected may be included on the trial.
- •Pregnant or breastfeeding women, or individuals actively trying to conceive
- •History of osteoporosis or bone fractures/loss
- •Hypersensitivity to the active substance or to any of the excipients in tenofovir disoproxil fumarate, lamivudine and/or doravirine formulations
- •Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
研究组 & 干预措施
immediate switch arm
Experimental arm (baseline visit switch group, N=30): One DOR/TDF/3TC tablet taken orally once daily for 48 weeks.
Virally suppressed participants on a stable combined ART regimen will be randomised (1:1) to an immediate switch to 3TC/TDF/DOR (immediate switch arm, N=30) for the duration of the 48-week study, or to maintaining their current cART followed by a switch to 3TC/TDF/DOR from week 24-48 (delayed switch arm, N=30). Participants will be monitored for the length of the study (48 weeks) plus a 30-day follow-up period.
干预措施: DELSTRIGO 100Mg-300Mg-300Mg Tablet (Drug)
delayed switch arm
Control arm (deferred switch group, N=30): Participants will continue their current triple cART regimen for 24 weeks, and then switched to taking one TDF/3TC/DOR tablet orally once daily (24 -48 weeks).
Virally suppressed participants on a stable combined ART regimen will be randomised (1:1) to an immediate switch to 3TC/TDF/DOR (immediate switch arm, N=30) for the duration of the 48-week study, or to maintaining their current cART followed by a switch to 3TC/TDF/DOR from week 24-48 (delayed switch arm, N=30). Participants will be monitored for the length of the study (48 weeks) plus a 30-day follow-up period.
干预措施: DELSTRIGO 100Mg-300Mg-300Mg Tablet (Drug)
结局指标
主要结局
To quantify the effect on lipid profile
时间窗: 24 weeks
To quantify the effect on lipid profile (change from baseline in total fasting cholesterol to Week 24) of switching from suppressive, stable cART containing ABA/3TC or TAF/FTC plus dolutegravir or bictegravir to Delstrigo (TDF/3TC/DOR) in HIV positive patients.
次要结局
- Hepatic steatosis and fibrosis by transient elastography-CAP (FibroScan® with the CAP probe)(48 weeks)
- Quality of Life (EuroQoL questionnaire)(48 weeks)
- Sleep quality (Pittsburgh Sleep Quality Index questionnaire)(48 weeks)
- Percentage of patients with treatment-related adverse events by week 48(48 weeks)
- Median change in body fat content (g) measured by Total body dexa at week 24 and 48(48 weeks)
- Body composition changes when measured by waist circumference at week 24 and 48(48 weeks)
- Change in insulin sensitivity from baseline to week 24 and 48 by HOMA-IR (glucose & insulin levels)(48 weeks)
- PBMC cholesterol and cholesteryl levels(48 weeks)
- Adipocytokines by assessing adiponectin, leptin(48 weeks)
- Pituitary hormones (TSH, LH, FSH, IGF-1, Testosterone)(48 weeks)
- Estimated cardiovascular risk (QRISK3 equation)(48 weeks)
- Estimated cardiovascular risk (D:A:D equation)(48 weeks)
- Dietary preferences (using Food preference questionnaire for adolescents and adults)(48 weeks)
- Renal safety by uPCR(48 weeks)
- Renal safety by eGFR(48 weeks)