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

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.

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