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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01869634
Recruitment Status : Completed
First Posted : June 5, 2013
Results First Posted : March 4, 2020
Last Update Posted : March 4, 2020
Information provided by (Responsible Party):
University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Infection Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine daily Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
Study Start Date : June 2013
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: HIV positive naive to ART
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.
Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine daily
Other Name: darunavir (Prezista®) 800 mg with ritonavir 100 mg and Truvada® to be taken once daily

No Intervention: normal control volunteers
HIV negative age-matched controls will undergo the same interventions and procedures without receiving ART at study entry and after 12 months.

Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline, 12 months ]
    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 :
  1. Change in Percentage of Total Artery Diameter [ Time Frame: Baseline, 12 months ]
    computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy

Other Outcome Measures:
  1. Change in Systemic Immune Activation [ Time Frame: Baseline, 12 months ]
    Change in systemic immune activation, as measured by change in plasma cytokine levels (IL-6).

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01869634

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United States, California
University of California Davis
Sacramento, California, United States, 95617
Sponsors and Collaborators
University of California, Davis
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Responsible Party: University of California, Davis Identifier: NCT01869634    
Other Study ID Numbers: 394080
IIS RFA _Asmuth:TMC114HIV2029 ( Other Identifier: Other )
First Posted: June 5, 2013    Key Record Dates
Results First Posted: March 4, 2020
Last Update Posted: March 4, 2020
Last Verified: February 2020
Keywords provided by University of California, Davis:
cardiovascular risk
systemic immune activation
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Virus Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors