Phase 4
Completed N=44
A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy
Source: ClinicalTrials.gov NCT00870363 ↗Enrolled (actual)
44
Serious AEs
0.0%
Results posted
Feb 2017
Primary outcomePrimary: Change in the Density of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Following Antiretroviral Therapy Regimen — 24; 89; 119; 566 cells/mm^2 — p=>0.05
◆ Published Evidence
Highly cited
128citations · ~13 / year
Correction: Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.
Summary
This research study is being done to find out how the immune system in the small intestines improves after taking antiretroviral (anti-HIV) medications. Biopsies (small snips of tissue) will be taken from the part of the intestines just below the stomach, and will be studied in the laboratory. The main purpose of this study is to measure the increase in the numbers of immune cells in the intestines to see if this number is related to the amount of medication that reaches the intestinal tissue, and the amount of virus that is still hiding there.
Subjects are either normal control subjects without HIV or, are HIV positive and are about to start HIV medications. As part of this study, HIV positive patients will be randomized to receive one of three possible combinations of medications.
1. maraviroc (Selzentry) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) or
2. maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) or
3. efavirenz (Sustiva) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor)
Both Maraviroc and Raltegravir each represent new classes of medications in the way that they interfere with HIV making copies of itself. Maraviroc attaches to the surface of the T-cell that the virus uses to get into the cell and is therefore known as an entry inhibitor. Raltegravir blocks the virus from inserting itself into the DNA of the infected cell's nucleus and is therefore known as an Integrase Inhibitor. We hope to learn more about how antiretroviral drugs affect T cells and how immune function restores itself when HIV infection is treated.
Linked Publications (4)
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Correction: Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.
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Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation.
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Effects of Immunonutrition in Advanced Human Immunodeficiency Virus Disease: A Randomized Placebo-controlled Clinical Trial (Promaltia Study).
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Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in the Density of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Following Antiretroviral Therapy Regimen |
24; 89; 119; 566 | >0.05 |
| SECONDARY Trough Plasma and Tissue Drug Levels in Volunteers at the Time of the Upper Endoscopy |
94.5; 397; 2459; 0.7; 0.1; 11.1 | — |
| SECONDARY Change in HIV DNA Per 10^6 Cells in Duodenal Tissue Versus PBMC by Drug Regimen Received |
-1709; -2500; -1330; -16; -846; -325 | — |
| SECONDARY Change in GALT CD4+ and CD8+ T-cell Subpopulations (naïve and Memory Subsets) |
— | — |
| SECONDARY Lymphocyte Immune Function and Activation at Two Time Points Approximately Nine Months Apart in GALT; and Four Timepoints (Month 0, 3, 6, and 9) in Peripheral Blood |
— | — |
| SECONDARY Changes in CD4+ T-cell Numbers by Treatment Regimen |
221; 231; 194 | — |
| SECONDARY 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 |
— | — |
Eligibility Criteria
Inclusion Criteria
- Males and Females ages 18 years to 60 years inclusive
- HIV positive (no anticipated antiretroviral therapy adjustments/changes)
- CD4 count greater than or equal to 50 cells/ml within 30 days of screening
- CCR5 tropism by Trofile ES(TM)
- Can be on secondary prophylaxis with a history of AIDS defining illness
- All females of child-bearing potential must agree to use barrier methods to prevent pregnancy or be abstinent from sexual activity while on study.
- willing to sign consent form
- HIV Negative individuals will also be recruited for this study as a Control Group
Exclusion Criteria
- allergy to peanuts or soya (maraviroc contains soya lecithin)
- abnormal coagulation parameters (PT greater than or equal to 1.2 ULN)
- thrombocytopenia (platelet count less than 50, 000 within 6 weeks)
- known GI pathology
- contra-indications to upper endoscopy or conscious sedation
- anemia greater than grade 1
- any active acute opportunistic infection (OI) or therapy for acute OI within 30 days of entry into study
- positive pregnancy test
- aspirin, ibuprofen, warfarin, or other agents that interfere with the coagulation cascade taken within 1 week of endoscopy
Data sourced from ClinicalTrials.gov (NCT00870363) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.