Switching Virally Suppressed HIV-1 Infected Elderly Adults (Age ≥ 60 Years) Without Prior Confirmed Virological Failure From Current Anti-retroviral Regimen to Bictegravir, Emtricitabine and Tenofovir Alafenamide (B/F/TAF)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 520
- 试验地点
- 2
- 主要终点
- Change in BMD
研究概览
简要总结
BACKGROUND: Current Kenya National Anti-retroviral (ARV) Guidelines and World Health Organization (WHO) Guidelines recommend first-line therapy of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and dolutegravir (DTG) for adult people living with HIV (PLHIV). This regimen has limitations, particularly for the aging PLHIV who are more likely to have pre-existing comorbidities and higher risk of developing comorbidities, including osteopenia, osteoporosis, and renal insufficiency. Abacavir, the preferred alternative nucleoside reverse transcriptase inhibitor (NRTI) in Kenya, is associated with increased cardiovascular risk that also limits its use in elderly populations. B/F/TAF is highly efficacious, well tolerated, co-formulated in a small pill, and does not have the same bone, renal or cardiovascular risks associated with currently recommended regimens in Kenya. We are not aware of any clinical trial to date that has been fully powered to compare ARV regimens for the increasing population of elderly PLHIV.
BROAD OBJECTIVE: We will compare the efficacy, safety, and impact on bone mineral density of switching to B/F/TAF to that of remaining on current ARV regimen in a population of elderly patients (60 years old or greater) with no prior confirmed treatment failure in Kenya.
详细描述
BACKGROUND
Kenya has the fourth largest burden of HIV globally with close to 1.5 million people living with HIV, with the highest prevalence seen in the age group 45-54 years. As PLHIV live longer with early and wider access to ART, we will have an increasingly aging population of PLHIV. The current Kenya National Guidelines and World Health Organization guidelines recommend TDF/3TC/DTG as the preferred first-line regimen for adults. This regimen is efficacious, available as a single-tablet regimen, is relatively well tolerated, and has a reasonable safety profile, particularly in younger populations.
Managing older populations is more challenging due to the presence of multiple comorbidities including cardiovascular disease, renal disease and bone disease. TDF is known to cause both renal insufficiency and osteoporosis/osteopenia, and is not recommended for patients with pre-existing renal disease or osteoporosis. Guidelines recommend measurement of renal function before initiation of TDF and ongoing monitoring of renal function, which is a potential barrier to rapid antiretroviral therapy (ART) initiation and is not always available or feasible in resource limited settings. Measurement of bone mineral density is expensive and not routinely carried out in resource-limited settings and osteoporosis is often only detected after a fracture. Elderly patients are more likely to have contraindications to the use of TDF but identifying those with contraindications is either not done or is costly and/or can result in a delay in treatment. The current alternative to TDF in many countries is abacavir (ABC), which is associated with an increased risk for cardiovascular events that is a particular concern for elderly patients, and has the disadvantage that it does not treat hepatitis B virus (HBV) co-infection.
RATIONALE
Tenofovir alafenamide (TAF) is a pro-drug of TDF whose pharmacokinetics allow for much lower dosing and reduced renal and bone toxicity compared to TDF, and is also approved to treat HBV. Switch from TDF to TAF has been associated with improvement in bone mineral density and reversion of osteoporosis.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to understand and comply with the protocol requirements, instructions and restrictions
- •Able and willing to give informed consent
- •Age 60 years or above
- •Documented HIV-1 infection as confirmed by HIV-antibody testing as per the Kenya National Guidelines
- •Has been receiving an ARV regimen for at least 24 weeks
- •Documented HIV-1 RNA viral load < 50 copies/ml at least 12 weeks prior to enrollment and no viral rebound between the first viral load < 50 copies/ml and the screening viral load
- •HIV-1 RNA viral load < 50 copies/ml at screening (within 28 days prior to enrollment)
排除标准
- •Confirmed treatment failure as defined by two consecutive HIV-1 RNA viral loads ≥ 50 copies/ml separated by at least 2 weeks, after at least 6 months on ART or after a documented HIV-1 RNA viral load < 50 copies/ml
- •Documented HIV-2 infection
- •Using any concomitant therapy disallowed as per the reference safety information and product labeling for the study drugs
- •Has AST and/or ALT at least 5-times greater than the upper limit of normal
- •Has a creatinine clearance (CrCl) below 50 ml/min (as estimated using the Cockcroft-Gault estimate for glomerular filtration rate)
- •Documented opportunistic infection within 4 weeks prior to the study enrolment
- •Investigator opinion that the patient should switch or discontinue any ARV in their current regimen immediately for clinical reasons (e.g. anemia with Hb < 9.5 g/dl while currently on azathioprine (AZT); HBsAg positive without currently being on TDF or TAF plus 3TC or FTC; experiencing adverse events associated with any ARV in current regimen deemed significant enough to warrant immediate change in regimen)
- •Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the study
- •History or presence of allergy to the study drugs or their components
- •BMD monitoring population will also exclude any participant with a pre-existing condition which is likely to decrease validity of bone mineral density estimations (including pre-existing vertebral or bilateral hip fractures, lytic or blastic metastases, bilateral hip arthroplasty, or lumbar spine internal fixation)
研究组 & 干预措施
Switch to B/F/TAF
Participants in this arm will switch from their current ARV regimen to the study drug B/F/TAF. This is an oral drug administered once daily for the duration of the study.
干预措施: Switch to B/F/TAF (Drug)
Continue current regimen
Participants in this arm will be maintained on their pre-enrollment ARV regimen for the duration of the study.
干预措施: Continue current regimen (Drug)
结局指标
主要结局
Change in BMD
时间窗: 48 weeks
Mean percentage change in lumbar spine BMD from baseline to week 48
Virologic failure at week 48
时间窗: 48 weeks
Proportion of participants with HIV-1 RNA ≥ 50 copies/ml at week 48 (by US Food and Drug Administration (FDA) snapshot algorithm)
次要结局
- Change in CD4(24, 48 and 96 weeks)
- Change in total cholesterol(24, 48 and 96 weeks)
- Change in body mass index(24, 48 and 96 weeks)
- Change in renal function(24, 48 and 96 weeks)
- Treatment success(24, 48 and 96 weeks)
- Change in BMD(24 and 96 weeks)
- Change in total hip BMD(24, 48 and 96 weeks)
- Virologic failure at week 24(24 and 96 weeks)
- Change in fracture risk as measured using the fracture risk assessment tool (FRAX)(24, 48 and 96 weeks)
- Change in patient satisfaction measured using the HIV treatment satisfaction questionnaire (HIVTSQ)(24, 48 and 96 weeks)
- Change in fasting blood glucose(24, 48 and 96 weeks)
- Laboratory and clinical adverse events(24, 48 and 96 weeks)
- Change in waist circumference(24, 48 and 96 weeks)
- Change in low-density lipoprotein(24, 48 and 96 weeks)
- Change in triglycerides(24, 48 and 96 weeks)
- Change in weight(24, 48 and 96 weeks)
- Change in total cholesterol to HDL ratio(24, 48 and 96 weeks)
- Change in waist hip ratio(24, 48 and 96 weeks)
- Type and frequency of genotypic resistance mutations(24, 48 and 96 weeks)
研究者
Loice Achieng
Principal Investigator
University of Nairobi