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

NCT ID: NCT01869634

Last Updated: 2020-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2016-12-31

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.

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.

Conditions

Human Immunodeficiency Virus Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

darunavir with ritonavir and fixed-dose viread+emtricitabine daily

Intervention Type: DRUG

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

darunavir with ritonavir and fixed-dose viread+emtricitabine daily

Intervention Type: DRUG

Other Intervention Names

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

Eligibility 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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California Davis

Sacramento, California, United States

Countries

United States

Other Identifiers

IIS RFA _Asmuth:TMC114HIV2029

Identifier Type: OTHER

Identifier Source: secondary_id

394080

Identifier Type: -

Identifier Source: org_study_id