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Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART

Primary Purpose

Human Immunodeficiency Virus Infection

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
darunavir with ritonavir and fixed-dose viread+emtricitabine daily
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Immunodeficiency Virus Infection focused on measuring HIV, cardiovascular risk, systemic immune activation

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Willing to sign consent form
  • Naïve to ART (remote ART use >5 years will be considered on a case by case basis)
  • No known GI or cardiovascular disease
  • Between the ages of 18 and 60
  • No active opportunistic infections or therapy for acute OI within 30 days of entry. Subjects can be on secondary prophylaxis with a history of AIDS defining illness.
  • All women of childbearing potential (WCBP) must have a negative urine pregnancy test before any of the invasive or radiation exposure study procedures.
  • Normal population should be free of chronic metabolic conditions such as diabetes, hypercholesterolemia, or coronary artery disease
  • There are no CD4+ T-cell count or HIV plasma viral load restrictions.

Exclusion Criteria:

  • Abnormal coagulation parameters (PT>1.2 upper limit of normal (ULN))
  • Thrombocytopenia (platelet count <50.000 within 6 weeks)
  • Contra-indications to upper endoscopy or conscious sedation
  • Anemia (>grade 1 [appendix 1])
  • Aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy.
  • Renal insufficiency (serum Creatinine >1.2 ULN)
  • History of chronic proteinuria that could impact viread use.
  • Allergy to contrast used for CT angiography
  • Requirement to take medications that are contraindicated with study ART regimen.

Sites / Locations

  • University of California Davis

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

HIV positive naive to ART

normal control volunteers

Arm Description

HIV subjects will receive open-label darunavir 800 mg in combination with ritonavir 100 mg tablets and fixed-dose combination viread + emtricitabine (Truvada®) to be taken once daily without regard to food. Subjects will undergo upper endoscopy, CT cardiac angiogram, intimal-medial thickening, and peripheral blood collection before and after 12 months of ART.

HIV negative age-matched controls will undergo the same interventions and procedures without receiving ART at study entry and after 12 months.

Outcomes

Primary Outcome Measures

Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV
CD4+ T-cells in the lamina propria/mm2 before and after 12 months of therapy compared to age-matched control volunteers without HIV.

Secondary Outcome Measures

Change in Percentage of Total Artery Diameter
computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy

Full Information

First Posted
June 1, 2013
Last Updated
February 24, 2020
Sponsor
University of California, Davis
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1. Study Identification

Unique Protocol Identification Number
NCT01869634
Brief Title
Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
Official Title
Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Potent HIV suppression with Darunavir-based antiretroviral therapy (ART) will lead to repopulation of gastrointestinal-associated lymphoid tissue (GALT) cluster of differentiation (CD)4+ T-cell populations, normalization of systemic immune activation, and improved HIV-associated cardiovascular disease (CVD) risk.
Detailed Description
Rationale Infection with HIV causes significant morbidity and mortality, even among individuals who are virologically suppressed with combination anti-retroviral therapy (ART). ART is effective in prolonging life and enabling individuals who are HIV positive to live near-normal life spans. However, these individuals are increasingly developing a number of chronic diseases of aging, such as atherosclerotic cardiovascular disease (ASCVD). The proposed studies will examine the role of highly active antiretroviral therapy in restoring the mucosal immunity and the systemic effect on immune activation, bacterial translocation, and change in HIV-associated cardiovascular disease risk.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus Infection
Keywords
HIV, cardiovascular risk, systemic immune activation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HIV positive naive to ART
Arm Type
Active Comparator
Arm Description
HIV subjects will receive open-label darunavir 800 mg in combination with ritonavir 100 mg tablets and fixed-dose combination viread + emtricitabine (Truvada®) to be taken once daily without regard to food. Subjects will undergo upper endoscopy, CT cardiac angiogram, intimal-medial thickening, and peripheral blood collection before and after 12 months of ART.
Arm Title
normal control volunteers
Arm Type
No Intervention
Arm Description
HIV negative age-matched controls will undergo the same interventions and procedures without receiving ART at study entry and after 12 months.
Intervention Type
Drug
Intervention Name(s)
darunavir with ritonavir and fixed-dose viread+emtricitabine daily
Other Intervention Name(s)
darunavir (Prezista®) 800 mg with ritonavir 100 mg and Truvada® to be taken once daily
Primary Outcome Measure Information:
Title
Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV
Description
CD4+ T-cells in the lamina propria/mm2 before and after 12 months of therapy compared to age-matched control volunteers without HIV.
Time Frame
Baseline, 12 months
Secondary Outcome Measure Information:
Title
Change in Percentage of Total Artery Diameter
Description
computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy
Time Frame
Baseline, 12 months
Other Pre-specified Outcome Measures:
Title
Change in Systemic Immune Activation
Description
Change in systemic immune activation, as measured by change in plasma cytokine levels (IL-6).
Time Frame
Baseline, 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Willing to sign consent form Naïve to ART (remote ART use >5 years will be considered on a case by case basis) No known GI or cardiovascular disease Between the ages of 18 and 60 No active opportunistic infections or therapy for acute OI within 30 days of entry. Subjects can be on secondary prophylaxis with a history of AIDS defining illness. All women of childbearing potential (WCBP) must have a negative urine pregnancy test before any of the invasive or radiation exposure study procedures. Normal population should be free of chronic metabolic conditions such as diabetes, hypercholesterolemia, or coronary artery disease There are no CD4+ T-cell count or HIV plasma viral load restrictions. Exclusion Criteria: Abnormal coagulation parameters (PT>1.2 upper limit of normal (ULN)) Thrombocytopenia (platelet count <50.000 within 6 weeks) Contra-indications to upper endoscopy or conscious sedation Anemia (>grade 1 [appendix 1]) Aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy. Renal insufficiency (serum Creatinine >1.2 ULN) History of chronic proteinuria that could impact viread use. Allergy to contrast used for CT angiography Requirement to take medications that are contraindicated with study ART regimen.
Facility Information:
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95617
Country
United States

12. IPD Sharing Statement

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Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART

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