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

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.

Timeline

Start

2009-04

Primary completion

2013-04

Completion

2013-04

Publications

• Results 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.
• 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.
• 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.
• 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.

Drugs

Indications