Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate COmpared With Bictegravir/Emtricitabine/Tenofovir Alafenamide in ART-Naïve People Living With HIV and Overweight or Obesity
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 306
- 试验地点
- 1
- 主要终点
- To determine the safety and tolerability of Doravirine/Lamivudine/Tenofovir compared with Bictegravir/Tenofovir Alafenamide/Emtricitabine in ART-naive people living with HIV at 144 weeks of treatment.
研究概览
简要总结
Background:Historically, HIV infection was associated with significant weight loss. However, weight gain is now commonly observed after initiating antiretroviral therapy (ART), particularly in individuals underweight at baseline. It remains unclear whether this weight gain reflects a "return to health" or results from drug-related or metabolic effects, and whether it persists beyond immune restoration. Recent evidence indicates that ART regimens containing second-generation integrase strand transfer inhibitors (INSTIs), such as bictegravir combined with tenofovir alafenamide, are associated with greater weight gain compared to other antiretroviral combinations, raising concerns about potential long-term metabolic consequences.Objective:To evaluate the effectiveness, safety, and tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) compared with Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) in ART-naïve people living with HIV (PWH) who are overweight or obese.Materials and Methods:This open-label, randomized clinical trial, approved by the Ethics and Scientific Research Committee (No. 3502), will be conducted at the Infectious Diseases Hospital of the National Medical Center "La Raza" from May 2025 to May 2027. ART-naïve PWH, recently diagnosed, with no prior use of pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), who do not require hospitalization, and have a body mass index (BMI) ≥25 kg/m² and body fat >20%, will be invited to participate. Participants will provide written informed consent and be randomized 1:1 to receive either DOR/3TC/TDF or BIC/FTC/TAF.
详细描述
Study Assessments Measurements: Laboratory tests, vital signs, and body composition (via bioimpedance) will be assessed at weeks 4, 12, 24, 36, 48, 72, 96, 120, and 144. HIV viral load and CD4+ count will be measured at weeks 12, 24, 48, 72, 96, 120, and 144.Statistical Methods: Non-probabilistic sampling will be used. Data distribution will be evaluated with the Kolmogorov-Smirnov test. Descriptive statistics (means, medians, percentages) will be reported. Between-group comparisons will use the Mann-Whitney U test for continuous variables and chi-square or Fisher's exact test for categorical variables. Longitudinal analysis at weeks 12, 24, 48, 96, and 144 will employ the Wilcoxon test. A p-value ≤0.05 with a 95% confidence interval will indicate statistical significance.Study ProcedureEligible ART-naïve PWH attending the HIV clinic will be identified and invited to participate. After providing informed consent, participants will be informed that participation is voluntary and can be withdrawn at any time without consequences.
Baseline Visit
- Data Collection: A medical interview will gather sociodemographic, clinical, and comorbidity data, as well as lifestyle habits (diet, physical activity, alcohol use, smoking).
- Anthropometric Measurements: Conducted using a 4-point segmental bioimpedance scale (FitScan Segmental Body Composition Monitor C-545F) to assess weight, water percentage, muscle mass, bone mass, and fat percentage. Waist and hip circumference, blood pressure, heart rate, respiratory rate, and oxygen saturation will also be measured.
- Laboratory Assessments: Include glucose, creatinine, cystatin C, serum and urinary electrolytes, lipid profile, liver function tests, elastography (visceral and subcutaneous fat), complete blood count, HIV viral load, CD4+ count, hepatitis B and C serologies, and VDRL.
Randomization and Follow-Up Participants will be randomized using the MEDSHARING digital system to either DOR/3TC/TDF or BIC/FTC/TAF. Follow-up visits will occur at specified intervals through week 144. Adverse events will be monitored using the DAIDS grading scale. Neuropsychiatric assessments will use the Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Patient Health Questionnaire (PHQ-9). Treatment satisfaction and distress will be evaluated with the HIV Treatment Satisfaction Questionnaire (HIVTSQ) and HIV Symptom Distress Module (HIVSDM).
Sampling and Sample Size
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (≥18 years) with confirmed HIV diagnosis, ART-naïve
- •Signed informed consent
- •HIV-1 RNA ≥1000 copies/mL
- •No history of PrEP or PEP failure
- •BMI ≥25 kg/m² and body fat >20%
- •Stable treatment for dyslipidemia (if applicable)
- •No planned medication changes affecting weight
- •Willingness to adhere to assigned ART
- •Recent HIV-1 RNA and CD4+ results
- •GFR (CKD-EPItip) ≥60 mL/min
- •ALT and AST <90 IU/L
- •Willingness to report dietary or physical activity changes during follow-up Non-Inclusion Criteria
- •Uncontrolled diabetes
- •Recent changes in insulin or hypoglycemic drugs (<3 months)
- •Active malignancy
- •History of bariatric surgery
- •Allergies to study drugs
- •Hepatitis B and/or C coinfection
- •GFR <60 mL/min (CKD-EPI)
- •Drug interactions with ART regimens
- •Recent (60 days) use of anorectic drugs
- •Recent (30 days) hospitalization for severe illness
- •Unstable hypothyroidism
排除标准
- •Loss of social security coverage
- •Newly discovered allergy to study drugs
- •Withdrawal of consent
- •Hepatitis B or C infection acquired during follow-up
- •Use of psychiatric or thyroid medications without a stable dose for ≥12 weeks
- •Initiation or discontinuation of medications affecting weight after enrollment
- •Unplanned bariatric surgery
研究组 & 干预措施
BIC/TAF/FTC
Bictegravir/ tenofovir alafenamide/ emtricitabine 50/ 25/ 200 mg. It is the usual therapy, consisting of 3 drugs in a single tablet, based on an integrase inhibitor, and 2 nucleoside analogues, it is the experimental group
干预措施: BIC/FTC/TAF (Drug)
DOR/3TC/TDF
Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100/300/300 mg Non-nucleoside reverse transcriptase inhibitor (doravirine) Nucleoside reverse transcriptase inhibitors (lamivudine, tenofovir disoproxil fumarate)
干预措施: DOR/3TC/TDF (Drug)
结局指标
主要结局
To determine the safety and tolerability of Doravirine/Lamivudine/Tenofovir compared with Bictegravir/Tenofovir Alafenamide/Emtricitabine in ART-naive people living with HIV at 144 weeks of treatment.
时间窗: 144 weeks
Number of participants with treatment-related adverse events as assessed of serious adverse events (WHO grade 3 or 4) for PWH treated with DOR/TDF/3TC or BIC/FTC/TAF at 144 weeks, expressed in proportions of new cases.
Evaluate the effectiveness and safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) compared with Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
时间窗: 144 weeks of follow-up with interim analysis at 48 and 96 weeks
Effectiveness: Number of participants with viral load measurement (HIV-1 RNA) \<50 copies/mL at 144 weeks of follow-up for PWH treated with DOR/3TC/TDF or BIC/FTC/TAF,BIC/FTC/TAF at 144 weeks,
次要结局
- To compare changes in lipid profile in people living with HIV (PLWH) treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide after initiating ART(144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks)
- To compare changes in body composition in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide before initiating ART(144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks)
- To compare changes in estimated glomerular filtration rate (eGFR) in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide after initiating TAR(144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks)
- To compare changes in cardiovascular risk using the Framingham Risk Score and the Pooled Cohort Equations (ASCVD AHA/ACC) in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide(144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks)
研究者
José Antonio Mata Marín
Principal investigator
Instituto Mexicano del Seguro Social