Transplantation and the Use of Raltegravir in HIV-Infected Patients
Condition: HIV Positive; Organ Transplant Recipient; Active Wait Listing for Organ Transplant
MeSH terms: HIV Seropositivity
Study type: Observational

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.
    

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