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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary: 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.
Sponsor: University of California, Davis

Current Primary Outcome: 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.


Original Primary Outcome: To correlate the increase in frequency 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 ]

Current Secondary Outcome:

Original Secondary Outcome:

  • To measure the trough plasma and tissue drug levels in volunteers at the time of the upper endoscopy [ Time Frame: nine months ]
  • To correlate the level of HIV RNA per gram of duodenal tissue versus plasma HIV load and drug regimen received [ Time Frame: nine months ]
  • To measure the change in GALT CD4+ and CD8+T-cell subpopulations (naive versus memory) in volunteers receiving raltegravir versus NNRTI [ Time Frame: nine months ]
  • To assess GALT immune function and activation in volunteers receiving raltegravir versus NNRTI [ Time Frame: nine months ]
  • To explore whether the treatment regimen correlates with the changes in CD3+/CD4+ T-cell numbers [ Time Frame: nine months ]
  • To compare the level of immune reconstitution with respect to absolute numbers of CD4+ T-cells, the relative proportion of T-cell subpopulations in the tissue, and immune activation to a cohort of normal controls [ Time Frame: nine months ]


Information By: University of California, Davis

Dates:
Date Received: April 16, 2008
Date Started: March 2008
Date Completion:
Last Updated: January 11, 2017
Last Verified: January 2017