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
Sponsor:
Information provided by (Responsible Party):
David Asmuth, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT01869634
First received: June 1, 2013
Last updated: NA
Last verified: June 2013
History: No changes posted

June 1, 2013
June 1, 2013
June 2013
December 2015   (final data collection date for primary outcome measure)
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.
Same as current
No Changes Posted
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.
Same as current
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.
Same as current
 
Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART

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.

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.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Human Immunodeficiency Virus Infection
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
  • 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.
    Intervention: Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine 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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
December 2016
December 2015   (final data collection date for primary outcome measure)

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.
Both
21 Years and older
Yes
Contact: Tammy Yotter, RN 916-914-6261 tammy.yotter@ucdmc.ucdavis.edu
Contact: David M Asmuth, MD 916-734-8695 david.asmuth@ucdmc.ucdavis.edu
United States
 
NCT01869634
IIS RFA _Asmuth:TMC114HIV2029, 394080-2
No
David Asmuth, MD, University of California, Davis
David Asmuth, MD
Not Provided
Not Provided
University of California, Davis
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP