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

• ClinicalTrials.gov Identifier: NCT00661960
• Recruitment Status: Completed
• First Posted: April 21, 2008
• Results First Posted: January 16, 2017
• Last Update Posted: May 30, 2017
• Sponsor: University of California, Davis
• Information provided by (Responsible Party): University of California, Davis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections; AIDS	Drug: raltegravir; Drug: efavirenz	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Raltegravir Therapy
• Study Start Date: March 2008
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
No Intervention: 1; HIV Negative volunteers
Active Comparator: 2; HIV-Positive volunteers taking raltegravir in combination with two other nucleoside reverse transcriptase inhibitors (NRTI) medications	Drug: raltegravir; 400mg tablet twice daily by mouth for nine months; Other Name: Isentress
Active Comparator: 3; 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; 600mg capsule once daily by mouth without regard to food; Other Name: Sustiva

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: nine months ]
   Duodenal tissue immune cell subsets were measured by flow cytometry.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, California

CARES Clinic

Sacramento, California, United States, 95814

UC Davis Medical Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Investigators

• Principal Investigator: David M. Asmuth, M.D.; University of California, Davis

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00661960
• Other Study ID Numbers: 200715792
• First Posted: April 21, 2008
• Results First Posted: January 16, 2017
• Last Update Posted: May 30, 2017
• Last Verified: May 2017

Keywords provided by University of California, Davis:

HIV Positive; AIDS; Antiretroviral Therapy; Gastrointestinal-Associated Lymphoid Tissue; Immune Reconstitution; treatment experienced

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Efavirenz; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors