Pilot Project of Virologic and Immunologic Correlates of GALT Immune Reconstitution Following Raltegravir Therapy

Study Overview
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Brief Summary
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This research is being done to study how the immune system in the small intestine improves after taking antiretroviral (anti-HIV) medications. The main purpose is to measure the increase in the numbers of immune cells in the intestine to see if one type of HIV medication gives different results than other types of HIV medications.

Detailed Description
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While the world-wide AIDS epidemic continues to impact millions of individuals, effective anti-HIV medications have substantially reduced morbidity and mortality for those patients able to adhere to combination regimens. Despite improved survival, durable virologic suppression, and increases in peripheral CD4+T-cell counts in patients receiving potent antiretroviral therapy (ART), immune reconstitution remains incomplete as measured by a number of additional surrogate markers. Perhaps critically important among areas of apparent incomplete immune recovery is the gastrointestinal-associated lymphoid tissue (GALT), where CD4+T-cells repopulate very slowly, if at all. Raltegravir is a new ART agent from a novel class of HIV inhibitors, integrase inhibitors, that results in rapid suppression of HIV and recovery of peripheral CD4+T-cells. This project proposes to examine whether volunteers receiving raltegravir recover GALT immune cells more completely than those taking comparator ART.

Official Title
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A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy

Conditions
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HIV Infections, AIDS

Intervention / Treatment
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* Drug: raltegravir
* Drug: efavirenz


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: willing to sign consent form no known GI pathology no anticipated antiretroviral therapy adjustments or changes males & females between the ages of 18 & 50 years no active opportunistic infections (OI) or therapy for OI within 30 days of entry can be on secondary prophylaxis with a history of AIDS defining illness per standard of care requirements, all females of child-bearing potential must agree to use barrier methods to prevent pregnancy or be abstinent from activity while on study Exclusion Criteria: abnormal coagulation parameters (PT > or equal to 1.2 ULN) thrombocytopenia (platelet count < 50,000 within 6 weeks) contra-indications to upper endoscopy or conscious sedation anemia (> or equal to grade 1) aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br>HIV Negative volunteers | |
| Active Comparator: 2<br>HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications | Drug: raltegravir<br>* 400mg tablet twice daily by mouth for nine months<br>* Other names: Isentress;|
| Active Comparator: 3<br>HIV-Positive volunteers taking efavirenz or any other non-nucleoside reverse transcriptase inhibitors (NNRTI) in combination with two other nucleoside reverse transcriptase inhibitor (NRTI) medications | Drug: efavirenz<br>* 600mg capsule once daily by mouth without regard to food<br>* Other names: Sustiva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Percentage of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Obtained From Volunteers to the Antiretroviral Therapy Regimen Over Time. | Duodenal tissue immune cell subsets were measured by flow cytometry. | nine months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment experienced, HIV Positive, AIDS, Antiretroviral Therapy, Gastrointestinal-Associated Lymphoid Tissue, Immune Reconstitution