Pilot Phase IV, Multicenter, Randomized, Open-label and Controlled Study to Assess the Evolution of Peripheral Body Fat Distribution After Switching From Zidovudine Containing Backbone to Truvada in HIV-1-infected Patients on HAART (RECOMB Study).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change From Baseline in Limb Fat at Week 48
研究概览
简要总结
This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine [FTC, 200 mg] and tenofovir disoproxil fumarate [TDF, 300 mg]) or who remained on a zidovudine- plus lamivudine-containing regimen. Subjects continued their protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).
详细描述
Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (PI or NRTI).
The use of nucleoside analogues, especially stavudine and zidovudine, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances.
As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the European Medicines Agency (EMA) in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection".
In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing zidovudine and lamivudine were randomized to switch to Truvada or to stay on their zidovudine- plus lamivudine-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).
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 infection documented by confirmed positive HIV-1 antibody test and/or positive polymerase chain reaction for HIV-1 ribonucleic acid (RNA).
- •Adult patients (over 18 years of age).
- •Current HAART regimen containing zidovudine + lamivudine at usual doses for at least 6 months.
- •Viral load < 50 copies/mL on the last two consecutive determinations, under zidovudine + lamivudine containing HAART regimen.
- •For women of childbearing potential, negative urine pregnancy test at screening visit.
- •Agreement to take part in the study and sign the informed consent.
- •Patients on lipid lowering treatment were allowed to participate in the study only if the lipid-lowering treatment (either statins or fibrates) was stable for at least 8 weeks prior to screening and it was not expected to change during the first 3 months of the study.
排除标准
- •Patients on current FTC or TDF therapy.
- •Patients with previous history of virological failure on an FTC or TDF-containing regimen.
- •Patients receiving a non-registered antiretroviral drug.
- •Patients receiving a triple-nucleoside antiretroviral combination.
- •Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of those drugs.
- •Known history of drug abuse or chronic alcohol consumption
- •Women who were pregnant or breast feeding, or female of childbearing potential who did not use an adequate method of contraception according to the investigator's judgment.
- •Active opportunistic infection or documented infection within the previous 4 weeks.
- •Documented active malignant disease (excluding Kaposi sarcoma limited to the skin).
- •Renal disease with creatinine clearance < 50 mL/min.
- •Concomitant use of nephrotoxic or immuno-suppressive drugs which could not be stopped without affecting the safety of the patient.
- •Receiving on-going therapy with systemic corticosteroids, Interleukin-2 or chemotherapy.
- •Patients who were not to be included in the study according to the investigator's criterion.
研究组 & 干预措施
Truvada
Truvada + NNRTI or PI.
干预措施: Truvada (Drug)
Zidovudine/lamivudine
Zidovudine/lamivudine + NNRTI or PI.
干预措施: Zidovudine/lamivudine (Drug)
结局指标
主要结局
Change From Baseline in Limb Fat at Week 48
时间窗: Baseline to Week 48
Limb fat was measured by DEXA. Change = Week 48 value minus baseline value.
次要结局
- Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa)(Baseline to Week 48)
- Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes)(Baseline to Week 48)
- Change From Baseline in Lactate Concentration(Baseline to Week 48)
- Percentage of Days for Which Participants Were Compliant With Study Drug(Baseline to Week 72)
- Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL(48 weeks)
- Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL(48 weeks)
- Percentage of Participants With Virologic Failure(48 weeks)
- Change From Baseline in Cluster Determinant 4 (CD4) Cell Count(Baseline to Week 48)
- Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL)(Baseline to Week 48)
- Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL)(Baseline to Week 48)
- Change From Baseline in Hemoglobin(Baseline to Week 48)
- Change From Baseline in Fasting Serum Triglycerides(Baseline to Week 48)
- Change From Baseline in Fasting Total Cholesterol(Baseline to Week 48)
- Percent Change From Baseline in Hematocrit(Baseline to Week 48)
- Change From Baseline in Waist Circumference/Hip Circumference Ratio(Baseline to Week 48)
- Percentage of Participants With Any Adverse Event(72 weeks)
- Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events.(48 weeks)