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

Not Applicable

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
2	raltegravir	HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications
3	efavirenz	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

Primary Outcome Measures

Name	Time	Method
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.	nine months	Duodenal tissue immune cell subsets were measured by flow cytometry.

Secondary Outcome Measures