search
Back to results

Renal Transplantation and Raltegravir in HIV-Infected Patients (ANRS153TREVE)

Primary Purpose

HIV-1 Infection, Chronic Renal Insufficiency

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Raltegravir
Sponsored by
ANRS, Emerging Infectious Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-1 Infection focused on measuring Raltegravir, Renal transplantation, HIV-1, Acute renal graft rejection

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Registration on the French national renal transplantation waiting list (Biomedicines Agency) for a living or cadaveric donor organ
  • HIV-1-infected patients treated by a three-drug ARV regimen
  • Immuno-virologic criteria at renal transplantation: undetectable viral load (<50 copies/mL) and CD4 >200/mm3 for at least three months on stable ARV
  • Age >18 years and <70 years
  • Effective contraception for women
  • Written informed consent
  • Patient with social security coverage

Exclusion Criteria:

  • Permanent:

    • Hepatic cirrhosis
    • Serious psychiatric illness history
    • EBV or HHV8 lymphoproliferation (lymphoma, systemic Kaposi's sarcoma or multifocal Castleman's disease)
    • History of PML
    • HTLV-1 seropositivity
    • Severe pulmonary or cardiovascular disease with poor short-term vital prognosis
    • Patient with AgHBs+
    • History of cryptosporidiosis
    • History of fungal infection with multi resistant fungi not likely to respond to oral antifungal therapy
    • Impossibility or refusal of Raltegravir switch, decision made by doctor or patient

  • Temporary:

    • Recent malignancy (between 2 and 5 years according to type)
    • HPV-related cervical or anal disease: carcinoma in situ, AIN III, CIN III in remission for less than three years
    • Active infection
    • HCV infection (PCR-positive)

Sites / Locations

  • Hôpital Pellegrin, Service de Nephrologie, Transplantation Rénale, Dialyse
  • CHU De Caen, Service de Néphrologie Hémodialyse
  • Hôpital Henri Mondor, Service de Néphrologie Transplantation
  • Hôpital Kremlin Bicêtre, Service de Néphrologie
  • CHRU Lille, Service de néphrologie
  • CHU de Nantes, Service de Néphrologie et Immunologie Clinique
  • Hôpital Pasteur, Service de Néphrologie - Transplantation
  • Hopital Saint Louis, Service de Néphrologie
  • Hôpital Necker, Service de Néphrologie adulte
  • Hôpital TENON, Urgences Néphrologiques et Transplantation Rénale
  • Hôpital civil, Service de Néphrologie et Transplantation
  • Hôpital Foch, Service de Néphrologie Transplantation
  • Hôpital Rangueil, Service de Néphrologie, HTA, Dialyse, Transplantation
  • Hôpital Bretonneau, Service de Néphrologie

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Raltegravir

Arm Description

Raltegravir associated to an antiretroviral regimen without ritonavir boosted antiprotease

Outcomes

Primary Outcome Measures

Incidence of acute clinical renal graft rejection
Incidence of acute clinical renal graft rejection defined by 20% increase of serum creatinine, associated to histological features (Banff classification) 6 months after renal transplantation

Secondary Outcome Measures

Incidence of acute clinical and subclinical renal graft rejection
Incidence of acute clinical and subclinical renal graft rejection up to 1 year after renal transplantation defined only by renal histology (without creatinine modification). Histology is performed on routine renal graft biopsy 3 months and 1 year after transplantation.
One year graft survival
One year graft survival, compared to non HIV-infected transplanted patients, using data provided by French Biomedicines Agency
Patients' survival
Patients survival, compared to: - chronic dialysis HIV patients still listed on the transplantation waiting list - transplanted non-HIV patients using data provide by French Biomedicine Agency
Phenotyping of lymphocytic infiltrates in case of acute rejection
The aim of the immunological phenotyping is to analyse the expression of activation markers between different TCD4 and TCD8 sub-population, this phenotyping will be compared to those observed in acute cell-mediated rejection occurring in the historical cohort of Non-HIV patients. In addition, the rate and expression of Treg population will be evaluated.
Incidence of AIDS defined diseases and severe morbidity diseases after renal transplantation
Severe morbidity diseases include: pathological infections, malignancies, metabolic and cardiovascular diseases.
Immunological and virologic status after renal transplantation
Immunological (lymphocyte activation and inflammatory parameters) and virologic status (kinetics of viral replication: HIV RNA in blood, total HIV DNA in PBMC) monitoring after renal transplantation. These parameters will be compared with pre-transplant status.
Evaluation of the switch by raltegravir at the time of renal transplantation
Assessment of ARV medications change and introduction of raltegravir at the time of renal transplantation in terms of reduction of pharmacokinetic interaction between antiretroviral regimen including raltegravir and immunosupressive treatments. In addition, virological efficacy of antiretroviral treatment including Raltegravir will be evaluated.
Viral load control after switch by antiretroviral treatment including raltegravir after renal transplantation
The aim of this study is to evaluate at the time of renal transplantation the virologic efficiency after the switch by an antiretroviral regimen including Raltegravir in terms of viral load control an virological failure as Raltegravir is known for its low genetic barrier.
Survival and waiting period of HIV patients registered on French biomedicine agency for renal transplantation
Assessment of HIV patients' waiting period until renal transplantation and survival of patients registered on French biomedicine agency waiting-list compared to Non-HIV population (data provided by French Biomedicine Agency )
Measurement of Area under plasma concentration (AUC) variability of immunosuppressive drugs after introduction of antiretroviral regimen containing Raltegravir
Area under plasma concentration (AUC) of Raltegravir and immunosuppressive drugs (Tacrolimus and Mycophenolate Mophetyl) will be measured as well as residual concentration of Tacrolimus. This study is performed in order to verify immunosupressive treatments dosage adaptation.

Full Information

First Posted
October 3, 2011
Last Updated
July 11, 2016
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT01453192
Brief Title
Renal Transplantation and Raltegravir in HIV-Infected Patients
Acronym
ANRS153TREVE
Official Title
National, Multicenter, Phase III Prospective Trial About Clinical and Immunological Follow-up After Renal Transplantation in HIV-1 Infected Patients With End Stage Chronic Renal Insufficiency
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this study is to evaluate the incidence of acute renal graft rejection 6 months after transplantation in HIV-infected patients under three antiretroviral drugs regimen including Raltegravir.
Detailed Description
Antiretroviral treatment of HIV-1 Infection might interact with immunosuppressive treatments which increase rejection of renal graft incidence. In addition HIV infection may be modified together with cardiovascular risk. Patients participating to this study will receive after transplantation antiretroviral regimen including Raltegravir. Raltegravir treatment does not interact with immunosuppressive drugs and thus seems to be the treatment of choice to be associated with immunosuppressive drugs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection, Chronic Renal Insufficiency
Keywords
Raltegravir, Renal transplantation, HIV-1, Acute renal graft rejection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Raltegravir
Arm Type
Experimental
Arm Description
Raltegravir associated to an antiretroviral regimen without ritonavir boosted antiprotease
Intervention Type
Drug
Intervention Name(s)
Raltegravir
Other Intervention Name(s)
Isentress
Intervention Description
Introduction of Raltegravir 2 days after renal transplantation within an antiretroviral regimen without ritonavir boosted antiprotease
Primary Outcome Measure Information:
Title
Incidence of acute clinical renal graft rejection
Description
Incidence of acute clinical renal graft rejection defined by 20% increase of serum creatinine, associated to histological features (Banff classification) 6 months after renal transplantation
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Incidence of acute clinical and subclinical renal graft rejection
Description
Incidence of acute clinical and subclinical renal graft rejection up to 1 year after renal transplantation defined only by renal histology (without creatinine modification). Histology is performed on routine renal graft biopsy 3 months and 1 year after transplantation.
Time Frame
1 year
Title
One year graft survival
Description
One year graft survival, compared to non HIV-infected transplanted patients, using data provided by French Biomedicines Agency
Time Frame
1 year
Title
Patients' survival
Description
Patients survival, compared to: - chronic dialysis HIV patients still listed on the transplantation waiting list - transplanted non-HIV patients using data provide by French Biomedicine Agency
Time Frame
1 year
Title
Phenotyping of lymphocytic infiltrates in case of acute rejection
Description
The aim of the immunological phenotyping is to analyse the expression of activation markers between different TCD4 and TCD8 sub-population, this phenotyping will be compared to those observed in acute cell-mediated rejection occurring in the historical cohort of Non-HIV patients. In addition, the rate and expression of Treg population will be evaluated.
Time Frame
1 year
Title
Incidence of AIDS defined diseases and severe morbidity diseases after renal transplantation
Description
Severe morbidity diseases include: pathological infections, malignancies, metabolic and cardiovascular diseases.
Time Frame
1 year
Title
Immunological and virologic status after renal transplantation
Description
Immunological (lymphocyte activation and inflammatory parameters) and virologic status (kinetics of viral replication: HIV RNA in blood, total HIV DNA in PBMC) monitoring after renal transplantation. These parameters will be compared with pre-transplant status.
Time Frame
1 year
Title
Evaluation of the switch by raltegravir at the time of renal transplantation
Description
Assessment of ARV medications change and introduction of raltegravir at the time of renal transplantation in terms of reduction of pharmacokinetic interaction between antiretroviral regimen including raltegravir and immunosupressive treatments. In addition, virological efficacy of antiretroviral treatment including Raltegravir will be evaluated.
Time Frame
1 year
Title
Viral load control after switch by antiretroviral treatment including raltegravir after renal transplantation
Description
The aim of this study is to evaluate at the time of renal transplantation the virologic efficiency after the switch by an antiretroviral regimen including Raltegravir in terms of viral load control an virological failure as Raltegravir is known for its low genetic barrier.
Time Frame
1 year
Title
Survival and waiting period of HIV patients registered on French biomedicine agency for renal transplantation
Description
Assessment of HIV patients' waiting period until renal transplantation and survival of patients registered on French biomedicine agency waiting-list compared to Non-HIV population (data provided by French Biomedicine Agency )
Time Frame
1 year
Title
Measurement of Area under plasma concentration (AUC) variability of immunosuppressive drugs after introduction of antiretroviral regimen containing Raltegravir
Description
Area under plasma concentration (AUC) of Raltegravir and immunosuppressive drugs (Tacrolimus and Mycophenolate Mophetyl) will be measured as well as residual concentration of Tacrolimus. This study is performed in order to verify immunosupressive treatments dosage adaptation.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Registration on the French national renal transplantation waiting list (Biomedicines Agency) for a living or cadaveric donor organ HIV-1-infected patients treated by a three-drug ARV regimen Immuno-virologic criteria at renal transplantation: undetectable viral load (<50 copies/mL) and CD4 >200/mm3 for at least three months on stable ARV Age >18 years and <70 years Effective contraception for women Written informed consent Patient with social security coverage Exclusion Criteria: Permanent: Hepatic cirrhosis Serious psychiatric illness history EBV or HHV8 lymphoproliferation (lymphoma, systemic Kaposi's sarcoma or multifocal Castleman's disease) History of PML HTLV-1 seropositivity Severe pulmonary or cardiovascular disease with poor short-term vital prognosis Patient with AgHBs+ History of cryptosporidiosis History of fungal infection with multi resistant fungi not likely to respond to oral antifungal therapy Impossibility or refusal of Raltegravir switch, decision made by doctor or patient Temporary: Recent malignancy (between 2 and 5 years according to type) HPV-related cervical or anal disease: carcinoma in situ, AIN III, CIN III in remission for less than three years Active infection HCV infection (PCR-positive)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe GRIMBERT, MD
Organizational Affiliation
CHU Henri-Mondor
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dominique COSTAGLIOLA, PHD
Organizational Affiliation
INSERM U943
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital Pellegrin, Service de Nephrologie, Transplantation Rénale, Dialyse
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU De Caen, Service de Néphrologie Hémodialyse
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Hôpital Henri Mondor, Service de Néphrologie Transplantation
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hôpital Kremlin Bicêtre, Service de Néphrologie
City
Kremlin Bicêtre
ZIP/Postal Code
94275
Country
France
Facility Name
CHRU Lille, Service de néphrologie
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU de Nantes, Service de Néphrologie et Immunologie Clinique
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital Pasteur, Service de Néphrologie - Transplantation
City
Nice
ZIP/Postal Code
06002
Country
France
Facility Name
Hopital Saint Louis, Service de Néphrologie
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hôpital Necker, Service de Néphrologie adulte
City
Paris
ZIP/Postal Code
75743
Country
France
Facility Name
Hôpital TENON, Urgences Néphrologiques et Transplantation Rénale
City
Paris
ZIP/Postal Code
75970
Country
France
Facility Name
Hôpital civil, Service de Néphrologie et Transplantation
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Hôpital Foch, Service de Néphrologie Transplantation
City
Suresnes
ZIP/Postal Code
92151
Country
France
Facility Name
Hôpital Rangueil, Service de Néphrologie, HTA, Dialyse, Transplantation
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hôpital Bretonneau, Service de Néphrologie
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Links:
URL
http://www.anrs.fr
Description
French National Agency for Research on AIDS and viral Hepatitis

Learn more about this trial

Renal Transplantation and Raltegravir in HIV-Infected Patients

We'll reach out to this number within 24 hrs