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

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01869634

First Posted: June 5, 2013

Last Update Posted: May 30, 2017

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.

Information provided by (Responsible Party):

University of California, Davis

Purpose

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


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Emtricitabine Ritonavir Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by University of California, Davis:

Primary Outcome Measures:

Recovery of CD4 T-lymphocytes in GALT [ Time Frame: 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:

To measure the change in cardiovascular risk [ Time Frame: 12 months ]
computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy

Other Outcome Measures:

changes in systemic immune activation [ Time Frame: 12 months ]
decline in plasma cytokine levels (IL-6)


Enrollment:	37
Study Start Date:	June 2013
Study Completion Date:	December 2016
Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

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.

Eligibility

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

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.

Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT01869634

Locations


United States, California
University of California Davis
Sacramento, California, United States, 95617

Sponsors and Collaborators

University of California, Davis

More Information


Responsible Party:	University of California, Davis
ClinicalTrials.gov Identifier:	NCT01869634 History of Changes
Other Study ID Numbers:	394080 IIS RFA _Asmuth:TMC114HIV2029 ( Other Identifier: Other )
First Submitted:	June 1, 2013
First Posted:	June 5, 2013
Last Update Posted:	May 30, 2017
Last Verified:	May 2017

Keywords provided by University of California, Davis:


HIV cardiovascular risk systemic immune activation

Additional relevant MeSH terms:


Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Virus Diseases Immune System Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Ritonavir Darunavir Emtricitabine	Tenofovir 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

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