Transplantation and the Use of Raltegravir in HIV-Infected Patients
| Status: | Recruiting |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 13 - 80 |
| Updated: | 4/21/2016 |
| Start Date: | October 2012 |
| Contact: | Cameron R Wolfe, MD |
| Email: | cameron.wolfe@duke.edu |
| Phone: | 9196680789 |
Solid Organ Transplantation and the Use of Raltegravir in HIV-Infected Patients: An Observational Study of Pharmacokinetics, Safety, Tolerability and Efficacy
Raltegravir (RAL) is a preferred option for initial antiretroviral therapy in the most
recent HIV Treatment Guidelines and is emerging as a popular choice for use in the
specialized population of HIV-infected patients being considered for solid organ
transplantation. Data from HIV-infected persons with normal organ function have revealed few
raltegravir-associated metabolic complications compared to older antiretrovirals, and in
general, drug-drug interactions with raltegravir are infrequent. The absence of such
concerns appears to make raltegravir a potentially appealing option for antiretroviral
therapy in HIV-infected patients being considered for solid organ transplantation.
At present, however, little is known of the safety and long term tolerability of
RAL-containing regimens in persons undergoing solid organ transplantation. As more
HIV-infected patients undergo organ transplantation, there is a growing need for good data
on such things as the effect of dialysis on RAL concentrations, the potential interactions
with commonly used immunosuppressive drugs, and the pharmacokinetic (PK) /pharmacodynamic
(PD) characteristics in those with end stage organ failure, as well as those with
functioning grafts.
The proposed study will also examine transplant function and survival in HIV-infected
patients receiving RAL-containing ART and will compare it to HIV negative historic controls.
recent HIV Treatment Guidelines and is emerging as a popular choice for use in the
specialized population of HIV-infected patients being considered for solid organ
transplantation. Data from HIV-infected persons with normal organ function have revealed few
raltegravir-associated metabolic complications compared to older antiretrovirals, and in
general, drug-drug interactions with raltegravir are infrequent. The absence of such
concerns appears to make raltegravir a potentially appealing option for antiretroviral
therapy in HIV-infected patients being considered for solid organ transplantation.
At present, however, little is known of the safety and long term tolerability of
RAL-containing regimens in persons undergoing solid organ transplantation. As more
HIV-infected patients undergo organ transplantation, there is a growing need for good data
on such things as the effect of dialysis on RAL concentrations, the potential interactions
with commonly used immunosuppressive drugs, and the pharmacokinetic (PK) /pharmacodynamic
(PD) characteristics in those with end stage organ failure, as well as those with
functioning grafts.
The proposed study will also examine transplant function and survival in HIV-infected
patients receiving RAL-containing ART and will compare it to HIV negative historic controls.
Pre-transplant:
- Patients on stable antiretroviral regimens who undergo evaluation for transplantation
and are subsequently placed on the transplant waiting list will be considered for
inclusion in the study. The details of the cART for each patient will remain the sole
purview of the patient and the patient's HIV care provider.
- To be considered for solid organ transplantation, in addition to routine transplant
listing criteria, the patient must fulfill the following criteria:
1. non-pregnant adult patient with CD4 count >200/μL;
2. no concurrent active AIDS-defining infections or malignancy;
3. at least 24 months of well controlled HIV viremia, defined as <50 copies for the
majority of the time.
After all screening procedures have been completed to ensure eligibility, a pre-transplant
pharmacokinetic study will be done as described below. Using specimens obtained during 7
time points, patient-specific Cmax, Cmin and AUC determinations will be made using standard
calculation approaches. The PK data will also include samples drawn on dialysis days for
patients with End-stage renal failure:- pre-dialysis, arterial and venous concentrations
(Cin and Cout) at the beginning of dialysis, and post dialysis levels (to determine
individual hemodialysis extraction ratios).
Additional data to be collected include a Quality of Life questionnaire, SF-36, and a PHQ-9
depression screen which will be administered as a baseline test done at enrollment. Patients
will be asked to have a dual-emission X-ray absorptiometry (DEXA) scan prior to transplant
(unless this has been completed within two years of enrollment).
Peri-transplant Assessments:
In addition to the standard of care laboratory and imaging procedures that are done around
the time of organ transplantation, the following research samples will be collected:
- Pre-transplant - RAL concentrations
- In addition, the following information will be recorded from the subject's medical
record: full HIV and infective history and test results including CD4 count, and
percentage, HIV viral load, electrocardiography (to assess QTc interval), CMV-IgG/IgM,
Hepatitis B, C, D screens +/- viral loads if not already determined.
Post-transplant inpatient hospitalization
- RAL concentrations as well as HIV viral load and CD4/CD8 lymphocyte populations.
- In addition, the following information will be recorded from the subject's medical
record: test results including EKG (to assess QTc interval).
Post-transplant:
- RAL concentrations will be collected at Months 1 and 3 only.
- In addition to the routine post-transplant care, the following information will be
collected from the subject's medical records at study months 1, 3, 6, 9, 12, 24 post
transplant: CD4 count and %, HIV viral load (+/- genotype and integrase mutation
analysis if viral rebound occurs), Vitamin D, Basic Metabolic Panel (to calculate
ClCr), quantitative urinary creatinine and protein excretion. Patient side-effect card
will be ascertained by directed questioning from the study coordinator at each visit.
Repeat DEXA scan will be done at the 24 months post-transplant visit. Quality of Life
assessment and depression screening tools will be administered at the 6 and 24 month marks.
- Patients on stable antiretroviral regimens who undergo evaluation for transplantation
and are subsequently placed on the transplant waiting list will be considered for
inclusion in the study. The details of the cART for each patient will remain the sole
purview of the patient and the patient's HIV care provider.
- To be considered for solid organ transplantation, in addition to routine transplant
listing criteria, the patient must fulfill the following criteria:
1. non-pregnant adult patient with CD4 count >200/μL;
2. no concurrent active AIDS-defining infections or malignancy;
3. at least 24 months of well controlled HIV viremia, defined as <50 copies for the
majority of the time.
After all screening procedures have been completed to ensure eligibility, a pre-transplant
pharmacokinetic study will be done as described below. Using specimens obtained during 7
time points, patient-specific Cmax, Cmin and AUC determinations will be made using standard
calculation approaches. The PK data will also include samples drawn on dialysis days for
patients with End-stage renal failure:- pre-dialysis, arterial and venous concentrations
(Cin and Cout) at the beginning of dialysis, and post dialysis levels (to determine
individual hemodialysis extraction ratios).
Additional data to be collected include a Quality of Life questionnaire, SF-36, and a PHQ-9
depression screen which will be administered as a baseline test done at enrollment. Patients
will be asked to have a dual-emission X-ray absorptiometry (DEXA) scan prior to transplant
(unless this has been completed within two years of enrollment).
Peri-transplant Assessments:
In addition to the standard of care laboratory and imaging procedures that are done around
the time of organ transplantation, the following research samples will be collected:
- Pre-transplant - RAL concentrations
- In addition, the following information will be recorded from the subject's medical
record: full HIV and infective history and test results including CD4 count, and
percentage, HIV viral load, electrocardiography (to assess QTc interval), CMV-IgG/IgM,
Hepatitis B, C, D screens +/- viral loads if not already determined.
Post-transplant inpatient hospitalization
- RAL concentrations as well as HIV viral load and CD4/CD8 lymphocyte populations.
- In addition, the following information will be recorded from the subject's medical
record: test results including EKG (to assess QTc interval).
Post-transplant:
- RAL concentrations will be collected at Months 1 and 3 only.
- In addition to the routine post-transplant care, the following information will be
collected from the subject's medical records at study months 1, 3, 6, 9, 12, 24 post
transplant: CD4 count and %, HIV viral load (+/- genotype and integrase mutation
analysis if viral rebound occurs), Vitamin D, Basic Metabolic Panel (to calculate
ClCr), quantitative urinary creatinine and protein excretion. Patient side-effect card
will be ascertained by directed questioning from the study coordinator at each visit.
Repeat DEXA scan will be done at the 24 months post-transplant visit. Quality of Life
assessment and depression screening tools will be administered at the 6 and 24 month marks.
Inclusion Criteria:
1. non-pregnant adult patient with CD4 count >200/μL
2. no concurrent active AIDS-defining infections or malignancy
3. at least 24 months of well controlled HIV viremia, defined as <50 copies for the
majority of the time.
4. otherwise suitable transplant candidates, actively listed
5. currently taking Raltegravir for control of HIV infection
We found this trial at
1
site
2301 Erwin Rd
Durham, North Carolina 27710
Durham, North Carolina 27710
919-684-8111
Principal Investigator: Cameron R Wolfe, MD
Phone: 919-668-0789
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