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

Human Immunodeficiency Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01869634
• Other study ID #: 394080
• Secondary ID: IIS RFA _Asmuth:
• Status: Completed
• Phase: Phase 4
• Start date: June 2013
• Est. completion date: December 2016

Study information

• Verified date: February 2020
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus Infection
• Virus Diseases

Intervention

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

Locations

Country	Name	City	State
United States	University of California Davis	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Systemic Immune Activation	Change in systemic immune activation, as measured by change in plasma cytokine levels (IL-6).	Baseline, 12 months
Primary	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	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	Baseline, 12 months