A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy

NCT00870363 | Completed Phase 4 Results

• 1 other identifier: 200816535
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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. 1.maraviroc (Selzentry) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) or
2. 2.maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) or
3. 3.efavirenz (Sustiva) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor)

Conditions

HIV Infections

Keywords

HIV; HIV positive; Gastrointestinal Associated Lymphoid Tissue (GALT); GALT Immune Reconstruction; treatment naive

Outcome Measures

Primary Outcomes (1)

• Change in the Density of CD3+/CD4+ Cells Per Cubic Millimeter at the Effector Sites in the Duodenal Tissues Following Antiretroviral Therapy Regimen

  immunohistochemistry for CD3+/CD4+ cells counted manually within the lamina propria

  Baseline and nine months for 3 treatment cohorts and Baseline for the control group, which was only assessed at one time point

Secondary Outcomes (6)

• Trough Plasma and Tissue Drug Levels in Volunteers at the Time of the Upper Endoscopy

  nine months

• Change in HIV DNA Per 10^6 Cells in Duodenal Tissue Versus PBMC by Drug Regimen Received

  Baseline and nine months

• Change in GALT CD4+ and CD8+ T-cell Subpopulations (naïve and Memory Subsets)

  nine months

• 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

  nine months

• Changes in CD4+ T-cell Numbers by Treatment Regimen

  Baseline and nine months

Study Arms (4)

1

ACTIVE COMPARATOR

maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician

Drug: maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor)

2

ACTIVE COMPARATOR

maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician

Drug: maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor)

3

ACTIVE COMPARATOR

efavirenz or other NNRTI (non-nucleoside reverse transcriptase inhibitor) in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician

Drug: efavirenz [or other NNRTI (non-nucleoside reverse transcriptase inhibitor)]

4

NO INTERVENTION

HIV-negative

Interventions

maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) DRUG

maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician

Also known as: Selzentry

1

maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) DRUG

maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician

Also known as: Selzentry (maraviroc)

2

efavirenz [or other NNRTI (non-nucleoside reverse transcriptase inhibitor)] DRUG

efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician

Also known as: Sustiva

3

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

CARES Clinic

Sacramento, California, 95811, United States

Location

Related Publications (4)

• Serrano-Villar S, Sainz T, Ma ZM, Utay NS, Chun TW, Mann S, Kashuba AD, Siewe B, Albanese A, Troia-Cancio P, Sinclair E, Somasunderam A, Yotter T, Deeks SG, Landay A, Pollard RB, Miller CJ, Moreno S, Asmuth DM. Correction: Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naive to Antiretroviral Therapy: A Pilot Randomized Trial. PLoS Pathog. 2016 Mar 25;12(3):e1005540. doi: 10.1371/journal.ppat.1005540. eCollection 2016 Mar. No abstract available.

  PMID: 27015639 RESULT

• Serrano-Villar S, de Lagarde M, Vazquez-Castellanos J, Vallejo A, Bernadino JI, Madrid N, Matarranz M, Diaz-Santiago A, Gutierrez C, Cabello A, Villar-Garcia J, Blanco JR, Bisbal O, Sainz T, Moya A, Moreno S, Gosalbes MJ, Estrada V. Effects of Immunonutrition in Advanced Human Immunodeficiency Virus Disease: A Randomized Placebo-controlled Clinical Trial (Promaltia Study). Clin Infect Dis. 2019 Jan 1;68(1):120-130. doi: 10.1093/cid/ciy414.

  PMID: 29788075 DERIVED

• Asmuth DM, Thompson CG, Chun TW, Ma ZM, Mann S, Sainz T, Serrano-Villar S, Utay NS, Garcia JC, Troia-Cancio P, Pollard RB, Miller CJ, Landay A, Kashuba AD. Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy. J Infect Dis. 2017 Oct 17;216(7):813-818. doi: 10.1093/infdis/jix418.

  PMID: 28968888 DERIVED

• 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.

  PMID: 21436711 DERIVED

MeSH Terms

Conditions

HIV Infections; HIV Seropositivity

Interventions

Maraviroc; Raltegravir Potassium; efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrrolidinones; Pyrrolidines

Results Point of Contact

• Title: David M Asmuth
• Organization: University of California Davis Medical Center

dasmuth@ucdavis.edu

(916) 734-8695

Study Officials

• David M. Asmuth, MD

  University of California, Davis Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 27, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: May 30, 2017
• Results First Posted: February 10, 2017

Record last verified: 2017-05

Locations

US (1)