N/A
N=328
Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters
HIV Infection
Bottom Line
View on ClinicalTrials.gov: NCT00851799 ↗Enrolled (actual)
328
Serious AEs
—
Results posted
Jan 2016
Primary outcome: Primary: Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT) — 8.2; 10.7; 12.9 micron/year — p=0.013
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Emtricitabine/tenofovir disoproxil fumarate (Drug); Ritonavir (Drug); Atazanavir (Drug); Raltegravir (Drug); Darunavir (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Primary completion
- Jun 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT) |
8.2; 10.7; 12.9 | 0.013 sig |
| PRIMARY Change in Brachial Artery (BA) Flow Mediated Dilation (FMD) From Study Entry to Week 24 |
-0.05; -0.27; 0.15 | 0.53 |
| SECONDARY Change in Brachial Artery Flow Mediated Dilation (FMD) From Study Entry to Weeks 4 and 48 |
-0.04; 0.22; -0.15; -0.04; -0.08; -0.11 | — |
| SECONDARY Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48 |
0.002; 0.012; -0.005; -0.002; -0.004; 0.008 | — |
| SECONDARY Percent Change in Bone Mineral Density (BMD) of the Hip From Study Entry to Week 96 |
-3.7; -2.2; -3.3 | — |
| SECONDARY Percent Change in Bone Mineral Density (BMD) of the Lumber Spine From Study Entry to Week 96 |
-4.0; -1.6; -3.1 | — |
| SECONDARY Percent Change in Bone Mineral Density (BMD) of the Total Body From Study Entry to Week 96 |
-1.9; -0.9; -1.0 | — |
| SECONDARY Percent Change in Total Limb Fat From Study Entry to Week 96 |
9.8; 6.3; 7.9 | — |
| SECONDARY Percent Change in Trunk Fat From Study Entry to Week 96 |
10.8; 13.5; 9.7 | — |
| SECONDARY Percent Change in Lean Mass From Study Entry to Week 96 |
1.8; 1.7; 0.1 | — |
| SECONDARY Percent Change in Visceral Abdominal Fat (VAT) From Study Entry to Week 96 |
10.7; 16.2; 9.5 | — |
| SECONDARY Percent Change in Subcutaneous Abdominal Fat (SAT) From Study Entry to Week 96 |
10.3; 11.8; 11.4 | — |
| SECONDARY CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144 |
350; 343; 355; 509; 445; 464 | — |
| SECONDARY Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144 |
161; 133; 118; 209; 191; 194 | — |
| SECONDARY Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96 |
4; -7; 3; 9; -4; 7 | — |
| SECONDARY Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96 |
14; -12; 15; 6; -16; 2 | — |
| SECONDARY Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96 |
-1; -2; -3; 3; 3; 0 | — |
| SECONDARY Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96 |
0; -3; 1; 2; -2; 3 | — |
| SECONDARY Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96 |
3; 3; 2; 4; 4; 4 | — |
| SECONDARY Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96 |
4.0; 3.0; 3.0; 4.0; 3.0; 2.0 | — |
| SECONDARY Fold Change in D-dimer From Study Entry to Weeks 48 and 96 |
0.57; 0.73; 0.65; 0.52; 0.72; 0.65 | — |
| SECONDARY Fold Change in High Sensitivity C-reactive Protein (hsCRP) From Study Entry to Weeks 48 and 96 |
0.75; 0.88; 0.78; 0.85; 0.78; 1.31 | — |
| SECONDARY Fold Change in Interleukin-6 (IL-6) From Study Entry to Weeks 48 and 96 |
0.62; 0.71; 0.75; 0.89; 0.82; 0.89 | — |
| SECONDARY Fold Change in Soluble CD14 From Study Entry to Weeks 48 and 96 |
1.01; 0.91; 1.00; 0.98; 0.90; 0.98 | — |
| SECONDARY Fold Change in Soluble CD163 From Study Entry to Weeks 48 and 96 |
0.54; 0.62; 0.61; 0.51; 0.56; 0.58 | — |
| SECONDARY Fold Change in Percent Expression of CD38+HLADR+ on CD4+ (Percent) From Study Entry to Weeks 24 and 96 |
0.49; 0.51; 0.52; 0.38; 0.34; 0.37 | — |
| SECONDARY Fold Change in Percent Expression of CD38+HLADR+ on CD8+ (Percent) From Study Entry to Weeks 24 and 96 |
0.51; 0.56; 0.59; 0.35; 0.36; 0.38 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- Enrollment in A5257 and intent to enroll in A5001 (ALLRT)
- Signed informed consent
- For A5257 inclusion criteria, please see ClinicalTrials.gov identifier NCT00811954
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT00851799). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.