Clinical trial NCT01869634: Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
Official title: Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus Infection
Keywords: HIV
cardiovascular risk
systemic immune activation
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2013-06-05
Enrollment: 37
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Baseline, 12 months
Secondary outcomes:
measure: Change in Percentage of Total Artery Diameter
timeFrame: Baseline, 12 months
Other outcomes:
measure: Change in Systemic Immune Activation
timeFrame: Baseline, 12 months
Locations:
city: Sacramento
country: United States
facility: University of California Davis
state: California
Study officials:
References: