A Prospective, Longitudinal Study of Endothelial Function in HIV/HCV Coinfected Subjects (CTSI-PLACE)

Clinical and Translational Science Institute Prospective Longitudinal Assessment of Coinfected Subjects With HIV/Hepatitis C for Endothelial Function Study

The CTSI-PLACE Study is a study for men and women with HIV/hepatitis C co-infection or HIV only. The study looks at the impact of having hepatitis C virus in addition to HIV on risk for cardiovascular disease. Participants will undergo non-invasive assessment of cardiovascular disease risk through measurements of endothelial function and blood biomarkers at baseline and 1 year (or 4 weeks and 24 weeks after end of HCV treatment for those that undergo HCV treatment during study follow-up).

Study Overview

• Status: Completed
• Conditions: Hepatitis C; HIV

• Study Type: Observational
• Enrollment (Actual): 87

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • UCLA CARE Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV/HCV coinfected and HIV monoinfected adults with well-controlled HIV

Description

Inclusion Criteria

1. Men and women ≥ 18 years
2. Hepatitis C negative or chronic hepatitis C infection
3. Chronic HIV infection
4. CD4+ T-cell count > 200 cells/mm3
5. Plasma HIV-1 RNA < 50 copies/mL
6. On continuous and stable ART for at least 12 weeks
7. Ability and willingness to provide written informed consent.

Exclusion Criteria

1. Known cardiovascular disease
2. Diabetes requiring insulin therapy or hemoglobin A1c > 8%
3. Inability to conform to requirements for PAT testing
4. Decompensated liver disease
5. Other known causes of significant liver disease
6. Serious illness including acute liver-related disease and malignancy requiring systemic treatment or hospitalization within 12 weeks prior to study entry
7. Presence of active or acute AIDS-defining opportunistic infections (OIs) within 12 weeks prior to study entry
8. History of major organ transplantation with an existing functional graft and on immunosuppressive therapy
9. History of known vascular or autoimmune disease
10. Pregnancy
11. HCV treatment (any approved or investigational agents) within 24 weeks prior to study entry
12. Use of immune-based therapies or systemic corticosteroids within 12 weeks prior to study entry
13. Advanced renal insufficiency as defined by glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 or treatment by dialysis

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Group A (HIV/HCV coinfected)
Group B (HIV monoinfected)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT)	Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation)	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)	Serum hsCRP	Baseline
Reactive Hyperemia Index (RHI)	Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation)	Week 52
Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)	Serum hsCRP	Week 52
Insulin Resistance by HOMA-IR	fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405	Baseline
Insulin Resistance by HOMA-IR	fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405	Week 52
Framingham Risk Score (FRS), 10-year Risk (%)	Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome.	Baseline
Framingham Risk Score (FRS), 10-year Risk (%)	Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome.	Week 52
Change in RHI		Baseline to Week 52
Change in Level of Each Soluble Biomarker (Components of Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)	Change in serum hsCRP level	Baseline to Week 52
Change in HOMA-IR		Baseline to Week 52
Change in Framingham Risk Score (10-year Risk, %)	Change in estimated 10-year risk (% risk) for developing coronary heart disease (CHD). Positive value indicates increase in estimated 10-year risk for CHD from baseline to Week 52. Negative value indicates decrease in estimated 10-year risk for CHD from baseline to Week 52.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Kara W. Chew, M.D., M.S., University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: October 30, 2015
• First Submitted That Met QC Criteria: November 3, 2015
• First Posted (Estimate): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: HIV; cardiovascular risk; inflammation; Hepatitis C; endothelial function; metabolic disease
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: 12-001792 (CTSI-PLACE); N/A (Parent P30AI028697) (Other Grant/Funding Number: UCLA AIDS Institute/Center for AIDS Research); N/A (Parent UL1TR000124) (Other Grant/Funding Number: UCLA Clinical and Translational Science Institute); 52767 (Other Grant/Funding Number: Merck Investigator Studies Program)