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

University of California, Davis37 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Human Immunodeficiency Virus Infection

Interventions

darunavir with ritonavir and fixed-dose viread+emtricitabine dailyDRUG

Eligibility

Sex: ALLMin age: 21 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

University of California Davis

Sacramento, California, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline, 12 months

Secondary Outcomes

Change in Percentage of Total Artery Diameter

computerized axial tomography angiography of the coronary arteries (CT-angio) before and after 12-months of Darunavir therapy

Time frame: Baseline, 12 months

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.