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

NCT01869634 | Completed Phase 4 Results

• 2 other identifiers: 394080IIS RFA _Asmuth:TMC114HIV2029
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus Infection

Keywords

HIV; cardiovascular risk; systemic immune activation

Outcome Measures

Primary Outcomes (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

  CD4+ T-cells in the lamina propria/mm2 before and after 12 months of therapy compared to age-matched control volunteers without HIV.

  Baseline, 12 months

Secondary Outcomes (1)

• Change in Percentage of Total Artery Diameter

  Baseline, 12 months

Other Outcomes (1)

• Change in Systemic Immune Activation

  Baseline, 12 months

Study Arms (2)

HIV positive naive to ART

ACTIVE COMPARATOR

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

normal control volunteers

NO INTERVENTION

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

Interventions

darunavir with ritonavir and fixed-dose viread+emtricitabine daily DRUG

Also known as: darunavir (Prezista®) 800 mg with ritonavir 100 mg and Truvada® to be taken once daily

HIV positive naive to ART

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

University of California Davis

Sacramento, California, 95617, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Darunavir; Ritonavir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Results Point of Contact

• Title: Dr. David Asmuth, Professor of Medicine
• Organization: University of California, Davis Health, Department of Internal Medicine

dasmuth@UCDAVIS.EDU

916-734-8695

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2013
• First Posted: June 5, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 4, 2020
• Results First Posted: March 4, 2020

Record last verified: 2020-02

Locations

US (1)