Hepatitis C, HIV
Conditions
Keywords
endothelial function, cardiovascular risk, HIV, Hepatitis C, metabolic disease, inflammation
Brief summary
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).
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
University of California, Los Angeles
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT) | Baseline | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reactive Hyperemia Index (RHI) | Week 52 | 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) |
| Insulin Resistance by HOMA-IR | Baseline | fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405 |
| Framingham Risk Score (FRS), 10-year Risk (%) | Baseline | 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. |
| Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | Baseline | Serum hsCRP |
| 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) | Baseline to Week 52 | Change in serum hsCRP level |
| Change in HOMA-IR | Baseline to Week 52 | — |
| Change in Framingham Risk Score (10-year Risk, %) | Baseline to Week 52 | 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. |
| Change in RHI | Baseline to Week 52 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A (HIV/HCV Coinfected) HIV+, HCV viremic at study entry | 45 |
| Group B (HIV Monoinfected) HIV+, HCV negative at study entry | 41 |
| Total | 86 |
Baseline characteristics
| Characteristic | Group A (HIV/HCV Coinfected) | Group B (HIV Monoinfected) | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 52 years | 52 years |
| Body mass index (kg/m2) | 27.6 kg/m2 | 26.0 kg/m2 | 26.3 kg/m2 |
| CD4+ T cell count | 587 cells/mm3 | 636 cells/mm3 | 612 cells/mm3 |
| Dyslipidemia | 7 Participants | 25 Participants | 32 Participants |
| Hypertension | 11 Participants | 7 Participants | 18 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black Non-Hispanic | 17 Participants | 10 Participants | 27 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 17 Participants | 20 Participants | 37 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White Non-Hispanic | 9 Participants | 8 Participants | 17 Participants |
| Sex/Gender, Customized Gender Men | 38 Participants | 35 Participants | 73 Participants |
| Sex/Gender, Customized Gender Transgender women | 3 Participants | 2 Participants | 5 Participants |
| Sex/Gender, Customized Gender Women | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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)
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT) | 1.98 ratio |
| Group B (HIV Monoinfected) | Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT) | 2.15 ratio |
Secondary
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.
Time frame: Baseline to Week 52
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Change in Framingham Risk Score (10-year Risk, %) | 1.0 percent |
| Group B (HIV Monoinfected) | Change in Framingham Risk Score (10-year Risk, %) | 0 percent |
Secondary
Change in HOMA-IR
Time frame: Baseline to Week 52
Population: All participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Change in HOMA-IR | 0.34 HOMA-IR score |
| Group B (HIV Monoinfected) | Change in HOMA-IR | 0.28 HOMA-IR score |
Secondary
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
Time frame: Baseline to Week 52
Population: All participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | 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) | 0.40 mg/L |
| Group B (HIV Monoinfected) | 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) | 0.00 mg/L |
Secondary
Change in RHI
Time frame: Baseline to Week 52
Population: All with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Change in RHI | -0.16 ratio |
| Group B (HIV Monoinfected) | Change in RHI | -0.03 ratio |
Secondary
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.
Time frame: Baseline
Population: All participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Framingham Risk Score (FRS), 10-year Risk (%) | 6.0 percent, 10-year risk |
| Group B (HIV Monoinfected) | Framingham Risk Score (FRS), 10-year Risk (%) | 6.0 percent, 10-year risk |
Secondary
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.
Time frame: Week 52
Population: All participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Framingham Risk Score (FRS), 10-year Risk (%) | 6.0 percent, 10-year risk |
| Group B (HIV Monoinfected) | Framingham Risk Score (FRS), 10-year Risk (%) | 5.0 percent, 10-year risk |
Secondary
Insulin Resistance by HOMA-IR
fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405
Time frame: Week 52
Population: All participants with available data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Insulin Resistance by HOMA-IR | 2.77 HOMA-IR score |
| Group B (HIV Monoinfected) | Insulin Resistance by HOMA-IR | 2.13 HOMA-IR score |
Secondary
Insulin Resistance by HOMA-IR
fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405
Time frame: Baseline
Population: All participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Insulin Resistance by HOMA-IR | 3.86 HOMA-IR score |
| Group B (HIV Monoinfected) | Insulin Resistance by HOMA-IR | 2.24 HOMA-IR score |
Secondary
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)
Time frame: Week 52
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Reactive Hyperemia Index (RHI) | 1.88 ratio |
| Group B (HIV Monoinfected) | Reactive Hyperemia Index (RHI) | 2.09 ratio |
Secondary
Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)
Serum hsCRP
Time frame: Week 52
Population: All participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | 1.05 mg/L |
| Group B (HIV Monoinfected) | Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | 1.0 mg/L |
Secondary
Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)
Serum hsCRP
Time frame: Baseline
Population: All participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A (HIV/HCV Coinfected) | Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | 0.6 mg/L |
| Group B (HIV Monoinfected) | Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) | 1.3 mg/L |