Cardiovascular, Anthropometric, and Skeletal Effects of Antiretroviral Therapy (ART) Initiation With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Plus Atazanavir/Ritonavir (ATV/r), Darunavir/Ritonavir (DRV/r), or Raltegravir (RAL): Metabolic Substudy of A5257
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 334
- 试验地点
- 26
- 主要终点
- Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT)
研究概览
简要总结
The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV-infected people who have never received anti-HIV therapy be treated with a triple drug regimen (commonly called combination antiretroviral therapy, cART). Since the introduction of cART, morbidity and mortality among HIV-infected patients has been dramatically reduced. However, metabolic, skeletal, and cardiovascular diseases have been increasingly reported among HIV-infected patients and may be attributable, in part, to the direct effects of cART. Much of our understanding of the development of these diseases, risk factors, and consequences of these disorders has been derived from clinical studies of HIV-infected persons receiving older antiretroviral agents.
A5260s was designed to examine the contributions of HIV-disease related factors and impact of newer antiretroviral drugs on the development of metabolic (such as blood vessels, blood sugar, cholesterol), skeletal, and cardiovascular diseases in people who have never received anti-HIV therapy. A5260s is a prospective substudy of a phase III randomized clinical trial A5257 (see ClinicalTrials.gov identifier: NCT00811954). A5257 was designed to look at different combinations of anti-HIV drugs that do not contain the medication efavirenz (EFV) and how well these drug combinations work to decrease the amount of HIV in the blood and to allow immune system recovery in people who have never received anti-HIV therapy. A5257 also examined drug tolerability and safety for the various drug combinations.
详细描述
A5260s is the optional, metabolic substudy of a phase III, prospective, randomized clinical trial (A5257). For complete details about the parent study A5257, please see ClinicalTrials.gov identifier NCT00811954.
Some participants in study A5257 were asked to participate in substudy A5260s. Not all participants were asked since A5260s only took place at a subset of A5257 sites. Participants who agreed to participate in substudy A5260s were enrolled at the same time as their enrollment in A5257. No interventions were given as part of A5260s, but all A5260s participants underwent blood draws, self-administered questionnaire responses (related to physical activity and body image), ultrasound scans to measure the thickness of the carotid artery in the neck and brachial artery flow mediated dilation in the arm, and computerized topography (CT) and dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density and body fat.
The duration of A5260s study was between 2 and 3 years (96 and 144 weeks), depending on when the participant enrolled. The study was designed to enroll a total of 330 participants with at least 110 per a group; each group represented a different randomized drug combination as defined and assigned by the main study A5257.
Cohort A: Atazanavir (ATV) + Ritonavir (RTV) + Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
Cohort B: Raltegravir (RAL) + FTC/TDF
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Enrollment in A5257 and intent to enroll in A5001 (ALLRT)
- •Signed informed consent
- •For A5257 inclusion criteria, please see ClinicalTrials.gov identifier NCT00811954
排除标准
- •Diabetes mellitus, (fasting plasma glucose ≥ 126 mg/dL on two occasions or on hypoglycemic medications).
- •Known cardiovascular disease (history of myocardial infarction [MI], coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, or peripheral arterial disease with ankle-brachial index of less than 0.9 or claudication)
- •Uncontrolled hypothyroidism or hyperthyroidism which in the opinion of the site investigator would affect substudy participation
- •Current use of statins, fish oil (greater than 2 grams per day), fibric acid derivatives, or niacin (more than 1000 mg per day) (NOTE: Current use of fish oil and niacin is defined as receiving treatment in the 8 weeks prior to study entry)
- •Intention to start pharmacological or surgical intervention for weight loss
- •Use of any ART in the 30 days before study entry
- •For A5257 exclusion criteria, please see ClinicalTrials.gov identifier NCT00811954
研究组 & 干预措施
Cohort B
RAL + FTC/TDF
FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
干预措施: Raltegravir (Drug)
Cohort B
RAL + FTC/TDF
FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (Drug)
Cohort A
ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (Drug)
Cohort A
ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
干预措施: Ritonavir (Drug)
Cohort A
ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
干预措施: Atazanavir (Drug)
Cohort B
RAL + FTC/TDF
FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
干预措施: Ritonavir (Drug)
Cohort C
DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (Drug)
Cohort C
DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
干预措施: Ritonavir (Drug)
Cohort C
DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
干预措施: Darunavir (Drug)
结局指标
主要结局
Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT)
时间窗: Study entry, week 144
Right common carotid artery intima-media thickness was measured by ultrasound scan at study entry and weeks 48, 96 and 144. The annual rate of change in right common carotid artery intima-media thickness (CIMT) was estimated over 144 weeks from study entry using mixed effects linear regression model that adjusted for screening HIV-1 RNA level and Framingham risk score stratification factors.
Change in Brachial Artery (BA) Flow Mediated Dilation (FMD) From Study Entry to Week 24
时间窗: Study entry, week 24
Brachial artery flow mediated dilation was measured by brachial artery reactivity tests. All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments. The change from study entry to week 24 in brachial artery FMD (%) was defined as the maximum FMD (%) calculated from resting heart rate (RH) 60 seconds and RH 90 seconds, relative to resting brachial artery diameter.
次要结局
- Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96(Study entry, weeks 4, 24, 48 and 96)
- Change in Brachial Artery Flow Mediated Dilation (FMD) From Study Entry to Weeks 4 and 48(Study entry, weeks 4 and 48)
- Percent Change in Trunk Fat From Study Entry to Week 96(Study entry, week 96)
- Percent Change in Lean Mass From Study Entry to Week 96(Study entry, week 96)
- Percent Change in Visceral Abdominal Fat (VAT) From Study Entry to Week 96(Study entry, week 96)
- Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96(Study entry, weeks 4, 24, 48 and 96)
- Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96(Study entry, weeks 4, 24, 48 and 96)
- Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96(Study entry, weeks 4, 24, 48 and 96)
- Fold Change in D-dimer From Study Entry to Weeks 48 and 96(Study entry, weeks 48 and 96)
- Fold Change in Percent Expression of CD38+HLADR+ on CD8+ (Percent) From Study Entry to Weeks 24 and 96(Study entry, weeks 24 and 96)
- Percent Change in Bone Mineral Density (BMD) of the Total Body From Study Entry to Week 96(Study entry, week 96)
- Percent Change in Subcutaneous Abdominal Fat (SAT) From Study Entry to Week 96(Study entry, week 96)
- Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48(Study entry, weeks 4, 24 and 48)
- Percent Change in Bone Mineral Density (BMD) of the Hip From Study Entry to Week 96(Study entry, week 96)
- Percent Change in Bone Mineral Density (BMD) of the Lumber Spine From Study Entry to Week 96(Study entry, week 96)
- Percent Change in Total Limb Fat From Study Entry to Week 96(Study entry, week 96)
- CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144(Study entry, weeks 24, 48, 96 and 144)
- Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144(Study entry to weeks 24, 48, 96, and 144)
- Fold Change in Percent Expression of CD38+HLADR+ on CD4+ (Percent) From Study Entry to Weeks 24 and 96(Study entry, weeks 24 and 96)
- Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96(Study entry, weeks 4, 24, 48 and 96)
- Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96(Study entry, weeks 4, 24, 48 and 96)
- Fold Change in High Sensitivity C-reactive Protein (hsCRP) From Study Entry to Weeks 48 and 96(Study entry, weeks 48 and 96)
- Fold Change in Interleukin-6 (IL-6) From Study Entry to Weeks 48 and 96(Study entry, weeks 48 and 96)
- Fold Change in Soluble CD14 From Study Entry to Weeks 48 and 96(Study entry, weeks 48 and 96)
- Fold Change in Soluble CD163 From Study Entry to Weeks 48 and 96(Study entry, weeks 48 and 96)