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

University of California (UC) Davis

Status and phase: Completed; Phase 4

Conditions: Human Immunodeficiency Virus Infection

Treatments: Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine daily

Study type: Interventional

Funder types: Other

Identifiers

NCT01869634

394080

IIS RFA _Asmuth:TMC114HIV2029 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 37 patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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37 participants in 2 patient groups

HIV positive naive to ART

Active Comparator group

Description:

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.

Treatment:

Drug: darunavir with ritonavir and fixed-dose viread+emtricitabine daily

normal control volunteers

No Intervention group

Description:

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