Clinical trial NCT00661960: Pilot Project of Virologic and Immunologic Correlates of GALT Immune Reconstitution Following Raltegravir Therapy
Official title: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
AIDS
Keywords: HIV Positive
AIDS
Antiretroviral Therapy
Gastrointestinal-Associated Lymphoid Tissue
Immune Reconstitution
treatment experienced
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2008-04-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: nine months
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: CARES Clinic
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
Study officials:
affiliation: University of California, Davis
name: David M. Asmuth, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Asmuth DM, Ma ZM, Mann S, Knight TH, Yotter T, Albanese A, Melcher GP, Troia-Cancio P, Hayes T, Miller CJ, Pollard RB. Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens. AIDS. 2012 Aug 24;26(13):1625-34. doi: 10.1097/QAD.0b013e3283546595.
citation: Ellis CL, Ma ZM, Mann SK, Li CS, Wu J, Knight TH, Yotter T, Hayes TL, Maniar AH, Troia-Cancio PV, Overman HA, Torok NJ, Albanese A, Rutledge JC, Miller CJ, Pollard RB, Asmuth DM. Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defic Syndr. 2011 Aug 15;57(5):363-70. doi: 10.1097/QAI.0b013e31821a603c.