Clinical trial NCT01793467: Transplantation and the Use of Raltegravir in HIV-Infected Patients
Official title: Solid Organ Transplantation and the Use of Raltegravir in HIV-Infected Patients: An Observational Study of Pharmacokinetics, Safety, Tolerability and Efficacy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Positive
Organ Transplant Recipient
Active Wait Listing for Organ Transplant
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2013-02-15
Enrollment: 17
Sex: ALL
Minimum age (years): 13
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV positive patients, awaiting or listed for organ transplantation, currently taking Raltegravir

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To examine raltegravir (RAL) in the management of HIV-infected persons listed for solid organ transplantation, with a focus on mortality and graft survival
timeFrame: 3+ years
Secondary outcomes:
measure: Assess Raltegravir viability as a long term HIV treatment drug for patients undergoing transplant
timeFrame: 3+ years
measure: determine the viability of grafted organs in patients with HIV infections
timeFrame: 3+ years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Cameron R Wolfe, MD
role: PRINCIPAL_INVESTIGATOR
References: