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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of California, Davis
Information provided by (Responsible Party):
David Asmuth, MD, University of California, Davis Identifier:
First received: June 1, 2013
Last updated: June 1, 2013
Last verified: June 2013
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
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Recovery of CD4 T-lymphocytes in GALT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To quantify restoration of GALT Lymphocyte Populations following Darunavir Therapy as measured by 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 ] [ Designated as safety issue: No ]
    To measure the change in CVD risk as determined by Intimal Medial Thickness (IMT), Brachial Artery Reactivity (BAR), and computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy and in comparison to age-matched and traditional CVD risk parameters-matched control volunteers without HIV.

Other Outcome Measures:
  • changes in systemic immune activation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine correlations between Immune Activation and Metabolic Profile as measured by CD38/HLA-DR co-expression on CD4+ and CD8+ lymphocytes in the PBMC's, and duodenal GALT and inflammatory cytokines in plasma and tissue before and after 12-months of Darunavir therapy and in comparison to age-matched control volunteers without HIV.

Estimated Enrollment: 40
Study Start Date: June 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (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.

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.

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01869634

Contact: Tammy Yotter, RN 916-914-6261
Contact: David M Asmuth, MD 916-734-8695

United States, California
University of California Davis Recruiting
Sacramento, California, United States, 95617
Contact: Tammy Yotter, RN    916-914-6261   
Principal Investigator: David M Asmuth, MD         
Sponsors and Collaborators
David Asmuth, MD
  More Information

Responsible Party: David Asmuth, MD, Professor, University of California, Davis Identifier: NCT01869634     History of Changes
Other Study ID Numbers: IIS RFA _Asmuth:TMC114HIV2029  394080-2 
Study First Received: June 1, 2013
Last Updated: June 1, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Sponsor-Investigator: David M Asmuth, MD, Professor, University of California Davis Medical Center, Sacramento, CA, USA

Keywords provided by University of California, Davis:
cardiovascular risk
systemic immune activation

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Virus Diseases
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Protease Inhibitors
Reverse Transcriptase Inhibitors processed this record on May 23, 2016