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Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00851799
First received: February 24, 2009
Last updated: December 5, 2013
Last verified: December 2013

February 24, 2009
December 5, 2013
May 2009
June 2013   (final data collection date for primary outcome measure)
  • Carotid artery intima-media thickness (CIMT) [ Time Frame: At study entry and Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
  • Absolute changes in brachial artery FMD from prior to treatment initiation [ Time Frame: At Weeks 4, 24, and 48 ] [ Designated as safety issue: No ]
  • Absolute changes in trunk fat from entry as measured by dual-energy x-ray absorptiometry (DXA) [ Time Frame: At study entry and Week 96 ] [ Designated as safety issue: No ]
  • Absolute changes in visceral fat as measured by single slice abdominal computed tomography (CT) scan [ Time Frame: At study entry and Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Fasting serum total cholesterol, high-density lipoprotein (HDL) cholesterol, direct low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, and apolipoprotein B-100 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Fasting glucose and insulin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Pro-inflammatory HDL and high sensitivity C-reactive protein (hsCRP) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • CD4/CD8 and CD38 levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Percent changes in bone mineral density of the lumbar spine and left hip [ Time Frame: At study entry and Week 96 ] [ Designated as safety issue: No ]
  • Carboxy-terminal collagen CTX and osteocalcin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Calculated tubular maximum for phosphate corrected for glomerular filtration rate (TmP/GFR) using urine phosphate [ Time Frame: At study entry and Weeks 4, 24, 48, 96, and 144. ] [ Designated as safety issue: No ]
  • Changes in self-reported fat distribution from entry as measured by the body image questionnaire [ Time Frame: At study entry and Week 144 ] [ Designated as safety issue: No ]
  • CIMT [ Time Frame: At Study Entry and Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
  • Absolute changes in brachial artery FMD from prior to treatment initiation [ Time Frame: At Weeks 4, 24, and 48 ] [ Designated as safety issue: No ]
  • Absolute changes in trunk fat from entry as measured by DXA [ Time Frame: At Study Entry and Week 96 ] [ Designated as safety issue: No ]
  • Absolute changes in visceral fat as measured by single slice abdominal CT [ Time Frame: At Study Entry and Weeks 48 and 96 ] [ Designated as safety issue: No ]
  • Fasting serum total cholesterol, HDL cholesterol, direct-LDL cholesterol, triglycerides, glucose, and apoliprotein B-100 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Fasting glucose and insulin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Pro-inflammatory HDL and hsCRP [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • CD8 and CD38 levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Percent changes in bone mineral density of the lumbar spine and left hip [ Time Frame: At study entry and Week 96 ] [ Designated as safety issue: No ]
  • Carboxy-terminal collagen CTX and osteocalcin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Calculated tubular maximum for phosphate corrected for glomerular filtration rate (TmP/GFR) using urine phosphate [ Time Frame: At study entry and Weeks 4, 24, 48, 96, and 144. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00851799 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters
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

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. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen has been shown to cause undesirable side effects for some patients and is therefore not an option for them. Alternative regimens are needed for these patients.

The main study will look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. It will also examine drug tolerability and safety for the various drug combinations.

This substudy of A5257 will further examine the effects of these new regimens on metabolic, skeletal, and cardiovascular factors.

Of the five anti-HIV drug classes, three are recommended as first-line regimens for patients who have never received anti-HIV treatment before (treatment naive): nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). The U.S. Department of Health and Human Services (HHS) guidelines recommend that treatment-naive HIV- infected people be treated with a triple drug regimen that includes two NRTIs + one NNRTI or two NRTIs + one PI as their initial treatment regimen.

According to data, an efavirenz (EFV)-containing regimen (two NRTIs + one NNRTI, with EFV as the NNRTI) requires fewer pills for the patient, has mild and few side effects, and is more effective in reducing viral load than other regimens, making it the preferred choice for most patients. However, for some patients, an EFV-containing regimen is not possible due to dangerous side effects, acquired NNRTI-resistant HIV virus, or other undesirable effects. For these patients, it is necessary to find alternative regimens with comparable safety and efficacy. The main study will examine how well different combinations of anti-HIV drugs work, including safety and drug tolerability for various combinations.

Some participants of A5257 will be asked to participate in this optional metabolic substudy of A5257. It will only take place at some study sites and may last up to 144 weeks, including time on A5257. The primary focus of this substudy is to examine carotid artery intima-media thickness (CIMT) as it relates to both ritonavir (RTV)- and raltegravir (RAL)-containing regimens. Randomization, stratification, treatment assignments, and study visits will be as per A5257. Female participants who become pregnant while in the study must inform the study staff immediately, and will subsequently be discontinued from the study without any further evaluations.

In the first 10 participant at each imaging site, the flow-mediated vasodilation (FMD) test, which measures cardiovascular risk, will be completed twice. This test will be performed on Week 24.

The need for this substudy stems from data showing an increasing number of HIV -infected patients with metabolic, skeletal, and cardiovascular diseases, which may be directly related to the effects of antiretroviral therapy. Conventional understanding of disease development, risk factors, and consequences pertain to persons receiving older antiretroviral drugs. Consequently, it is necessary to examine the impact of newer antiretroviral drugs on metabolic, skeletal, and cardiovascular factors. The purpose of this substudy is to understand the contributions of HIV disease-related factors and antiretroviral therapy to the development of metabolic, skeletal, and cardiovascular disease among HIV -infected patients.

Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Blood and urine samples will be collected and stored

Non-Probability Sample

HIV-infected participants currently enrolled in study A5257

  • HIV Infections
  • Treatment Naive
Not Provided
  • A
    Participants in Arm A of the main study undergoing treatment with atazanavir (ATV) + ritonavir (RTV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
  • B
    Participants in Arm B of the main study undergoing treatment with raltegravir (RAL) + FTC/TDF
  • C
    Participants in Arm C of the main study undergoing treatment with darunavir (DRV) + RTV + FTC/TDF
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
334
June 2013
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Enrollment in A5257 and intent to enroll in A5001 (ALLRT)
  • Signed informed consent
  • Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites

Exclusion Criteria:

  • Diabetes mellitus
  • 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 (less 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 before study entry)
  • Intention to start pharmacological or surgical intervention for weight loss
  • Use of any ART in the 30 days before study entry
  • Presence of decompensated cirrhosis
  • Pregnant or breastfeeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00851799
ACTG A5260s, 1U01AI068636, ACTG A5257 metabolic substudy
Not Provided
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Todd Brown, MD, PhD Johns Hopkins University
Study Chair: James Stein, MD University of Wisconsin, Madison
AIDS Clinical Trials Group
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP