Impact of Sirolimus and Maraviroc on CCR5 Expression and the HIV-1 Reservoir in HIV-infected Kidney Transplant Recipients

NCT02990312 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: HP-00072807
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this proof of concept, pilot study is to determine whether the unique combination of the human immunodeficiency virus (HIV) co-receptor antagonist, Maraviroc, and the mammalian target of rapamycin (mTOR) inhibitor, Sirolimus, in HIV-infected kidney transplant recipients has an impact on chemokine receptor 5 (CCR5) density, the HIV-reservoir, or rejection of the transplanted kidney. 15 HIV-infected kidney transplant recipients will be recruited and their immunosuppressant regimen will be changed to include an mTOR inhibitor (such as Sirolimus) unless they are already on one. In addition, Maraviroc will be added to their HIV regimen, unless they are already on Maraviroc. Blood will be taken to measure markers of the HIV reservoir, their CCR5 density and expression, and immune activation.

Conditions

Hiv; Kidney Transplant; HIV Reservoir; CCR5

Outcome Measures

Primary Outcomes (1)

• HIV viral reservoir

  total cellular HIV DNA

  96 weeks

Secondary Outcomes (10)

• Secondary measures of the HIV viral reservoir

  96 weeks

• Circulating HIV

  96 weeks

• CCR5 Receptor Density

  96 weeks

• CCR5 Expression

  96 weeks

• Acute cellular rejection

  96 weeks

Study Arms (1)

Sirolimus + Maraviroc

EXPERIMENTAL

Participants will be placed on the combination of Sirolimus and Maraviroc, unless they are already on one of these medications.

Drug: Sirolimus + Maraviroc

Interventions

Sirolimus + Maraviroc DRUG

Patients will be placed on the combination of Sirolimus and Maraviroc starting on Day 0 and followed for 96 weeks during which they will have regular monitoring of both clinical safety labs, Sirolimus levels, and research labs to look at the HIV reservoir, CCR5 density, and immune activation

Also known as: Rapamycin, Rapamune, Selzentry

Sirolimus + Maraviroc

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is able to understand and provide informed consent and comply with the study protocol
• Diagnosis of HIV infection based on medical record documentation, ELISA and western blot testing, or a record of a detectable HIV viral load
• Participant is \> or = 18 years
• CD4 T cell count \> or = 200 cells per microliter within 16 weeks prior to enrollment
• Most recent HIV-1 RNA \< 50 copies per milliliter within 16 weeks prior to enrollment
• Participant must be \> or = 6 months post-renal transplant
• GFR \>25 for a minimum of 6 months prior to enrollment
• On a maintenance immunosuppressive regimen for a minimum of 6 months prior to enrollment
• Female participants of child bearing age must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test within 30 days of enrollment and agree to use contraception during the study

You may not qualify if:

• Proteinuria at screening defined by spot urine protein to creatinine ratio \>1000 milligrams per gram
• The following active opportunistic infections: Ongoing chronic infections such as progressive multifocal leukoencephalopathy (PML), disseminated cryptococcosis, chronic cryptosporidiosis
• Active malignancy other than superficial skin neoplasms, vulvar intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), or anal intraepithelial neoplasia (AIN)
• Any history of augmented immunosuppression with induction immunosuppression regimens for the treatment of rejection in the 6 months prior to enrollment
• Known allergy or intolerance to maraviroc or sirolimus
• Pregnancy or breastfeeding
• Active substance abuse or mental health concerns that are judged to place a significant limitation on medication adherence by the PI.
• Triglyceride elevation at screening \> 750; or LDL-c \> 160 despite medical treatment
• Use of any investigational drugs within 30 days prior to screening
• History of serious adverse reactions to macrolide antibiotics, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and abdominal pain.
• Past or current medical problems not listed above which, at the discretion of the investigator, may pose additional risks from participation in the study, interfere with the participants ability to comply with study requirements or impact the quality or interpretation of data obtained from the study
• Known contraindication to the use of maraviroc or sirolimus
• Current and ongoing need for concomitant use of rifampin, rifabutin, rifapentine, St. John's wort, phenytoin, phenobarbital, carbamazepine or dofetilide
• Any current incompletely healed wounds

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Institute of human virology

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Sirolimus; Maraviroc

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jennifer S Husson, MD,MPH

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: December 13, 2016
• Study Start: May 1, 2017
• Primary Completion: July 17, 2019
• Study Completion: July 17, 2019
• Last Updated: December 16, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)