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

• Status: Withdrawn
• Trial end date: 2019-07-17
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Treatments: Everolimus; Maraviroc; Sirolimus

Criteria

Inclusion Criteria:

1. Patient is able to understand and provide informed consent and comply with the study protocol

2. Diagnosis of HIV infection based on medical record documentation, ELISA and western blot testing, or a record of a detectable HIV viral load

3. Participant is > or = 18 years

4. CD4 T cell count > or = 200 cells per microliter within 16 weeks prior to enrollment

5. Most recent HIV-1 RNA < 50 copies per milliliter within 16 weeks prior to enrollment

6. Participant must be > or = 6 months post-renal transplant

7. GFR >25 for a minimum of 6 months prior to enrollment

8. On a maintenance immunosuppressive regimen for a minimum of 6 months prior to enrollment

9. 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

Exclusion Criteria:

1. Proteinuria at screening defined by spot urine protein to creatinine ratio >1000 milligrams per gram

2. The following active opportunistic infections: Ongoing chronic infections such as progressive multifocal leukoencephalopathy (PML), disseminated cryptococcosis, chronic cryptosporidiosis

3. Active malignancy other than superficial skin neoplasms, vulvar intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), or anal intraepithelial neoplasia (AIN)

4. Any history of augmented immunosuppression with induction immunosuppression regimens for the treatment of rejection in the 6 months prior to enrollment

5. Known allergy or intolerance to maraviroc or sirolimus

6. Pregnancy or breastfeeding

7. Active substance abuse or mental health concerns that are judged to place a significant limitation on medication adherence by the PI.

8. Triglyceride elevation at screening > 750; or LDL-c > 160 despite medical treatment

9. Use of any investigational drugs within 30 days prior to screening

10. History of serious adverse reactions to macrolide antibiotics, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and abdominal pain.

11. 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

12. Known contraindication to the use of maraviroc or sirolimus

13. Current and ongoing need for concomitant use of rifampin, rifabutin, rifapentine, St. John's wort, phenytoin, phenobarbital, carbamazepine or dofetilide

14. Any current incompletely healed wounds