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Episode #20 – HIV & Solid Organ Transplants

20 Cover Art OPT

Summary

Are you HOPE-ing to learn more about organ transplantation in people living with HIV? Listen as Drs. Ashka Patel and Jennifer Husson take us through the pre- and post-transplant process for these patients.

Credits

Host(s): Ashka Patel, Sara Dong

Guest: Jennifer Husson

Writing: Ashka Patel, Sara Dong

Producing/Editing/Cover Art: Sara Dong

Infographics: Sara Dong

Our Guests

Jennifer Husson, MD

Dr. Husson graduated medical school at Northwestern University Feinberg School of Medicine.  She then completed her internal medicine residency and infectious diseases fellowship at the University of Maryland.  She completed additional training in infectious diseases in immunocompromised hosts at University of Maryland as well and continues to practice there.  She consults on the inpatient transplant ID service as well as seeing patients in the outpatient transplant clinic.  Jennifer also started a separate clinic to streamline the screening and care for HIV infected transplant candidates/recipients and the management of HCV post-transplant.

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Ashka Patel, DO

Dr. Patel completed her ID fellowship at the University of Maryland and is now an ID physician at Inova Hospital

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Culture

Jennifer loves going on hikes to explore the outdoors and spend time with family.  Some of her all-time favorite trails are in Maine at Acadia National Park and Baxter State Park.

Consult Notes

Consult Q

66 yo F with HIV and HCV/alcoholic cirrhosis who presents for new pre-liver transplant evaluation.

One-liner

66 yo F with HIV and HCV/alcoholic cirrhosis who presents for new pre-transplant evaluation and is followed for management post-transplant as well.

Key Notes

Jump to:

HIV+ Tx recipient criteria
HIV+ Tx + Hepatitis Co-infection
ART + Tx
Tx immunosuppression in hiv+ recipients
post-tx monitoring
HIV+ transplant + infection risk
outcomes
hiv-to-hiv tx & the hope act

General approach and considerations for the pre-transplant evaluation in patients living with HIV 

Centers require patients to have well-controlled HIV infection prior to transplant as well as no evidence of active opportunistic infection (OI) or uncontrolled HIV viremia.  There is no data to establish the exact time period patients should be controlled prior to transplant, but the general feeling is the longer the better.  Below are some general criteria for SOT in HIV-infected individuals.

 

Suggested criteria for transplantation in HIV+ individuals

  • CD4 > 200 during 3 mo prior to transplantation (>100 for livers)
  • Undetectable viral load on ART
  • On stable ART with adherence
  • Absence of OI and malignancy (or historic OI/malignancy that might recur)
  • Absence of chronic wasting and malnutrition
  • Appropriate/established follow up with HIV providers
  • Access to immunosuppressive medications therapeutic monitoring
  • Meet any center specific criteria

Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patient: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13499. doi: 10.1111/ctr.13499. Epub 2019 Apr 21. PMID: 30773688.

 

Are there times to consider possible exceptions to these criteria?

  • May consider allowing for lower CD4 counts in liver transplant recipients if thought to be related to primary disease
  • May consider allowing for detectable viremia in patients with ESLD and intolerance of ART related to severe liver disease, but HIV genotypics/phenotypic testing that are predictive of viral suppression on resumption of ART
  • There may also be a few situations where lower CD4 counts are considered in kidney transplant recipients who have been really well controlled and suppressed from HIV standpoint for years, but have experienced progressive downtrend in CD4 (that is likely unrelated to HIV but rather due to other comorbidities)

How does co-infection of HIV with HBV or HCV impact the evaluation?  

  • Those with co-infected HCV can be considered for transplantation assuming there is a plan for treatment of HCV prior to or early post-transplant
      • Allows them to potentially receive HCV+ organs as well
  • For those undergoing kidney transplant evaluation with HIV-hepatitis co-infection, patients need a good assessment of liver function prior to transplant, as typical liver enzymes can underestimate severity of liver disease in patients with HIV.  This can help with consideration of dual liver-kidney transplant if significant liver disease is present
      • Should undergo either transient elastography (fibroscan) or liver biopsy prior to listing
  • Those with HBV co-infection should be on ART that includes 2 drugs with activity against HBV (tenofovir alafenamide > tenofovir disoproxil fumarate, emtricitabine, lamivudine)
      • If no good option for HIV that uses one of the above, can potentially use entecavir

Assessing HIV ART regimens prior to transplant

Must think about drug interactions between anticipated transplant meds and ART — ALWAYS do a drug-interaction check to check for issues.  Here are a few important points:

  • Protease inhibitor-based regimens and cobicistat should be avoided if at all possible (due to DDI with both calcineurin inhibitors (CNI) and mTOR inhibitors)
      • PIs are the worst offenders.  Most significant DDI with CNI, but to lesser extent also mTOR inhibitors
          • As Jennifer explained, this interaction can be quite significant and requires a really drastic dose adjustment of CNI.  For example, a patient may need to move CNI dosing to weekly or once every 8-10days if also on a PI.  This makes it much harder to check for CNI drug monitoring and understand what their total exposure to CNI is.  While CNIs prevent rejection well, one of their toxicities in renal dysfunction, so this can be a vicious cycle, particularly in kidney transplant recipients.
      • Would try to avoid these medications and make changes prior to transplant, unless there are no other options.  If PI or cobi is needed, likely will need daily monitoring of levels to determine the optimal dosing for IS.
  • NNRTIs can impact CNI and mTOR inhibitors similar to PIs, but not quite as significant (can generally work around these)
      • NNRTIs induce clearance of drugs metabolized by CYP3A, so may need dose adjustments up front — but typically are easier to monitor afterwards
      • Rilpivirine is an exception that doesn’t seem to have interaction and can be used safely.  Rilpivirine is preferred NNRTI in this patient population
  • Integrase inhibitor-based (raltegravir, bictegravir, and dolutegravir) regimens are preferred due to their favorable safety profile and lack of DDIs
      • Would note that dolutegravir increases serum creatinine post-kidney transplant more profoundly since it inhibits tubular secretion of creatinine (not nephrotoxic and doesn’t change GFR — but something to keep in mind as Cr is scrutinized closely post-transplant)
  • Once daily ART regimens do not have easy renal dose adjustment
  • Jennifer also mentioned another drug interaction:
      • If using an H2 blocker or antacid, need to make sure these are being separated from ART
      • If on rilpivirine, can’t use PPIs
  • Mentioned previously, but a reminder that those with HBV+HIV co-infection should receive ART with two drugs with activity against HBV (TAF preferred to TDF)

Check out Table 2 for a nice summary of possible PK/PD DDI with ART and IS in the AST IDCOP guidelines

Jennifer spoke about immunosuppressive regimens for the HIV-infected transplant recipient.  The optimal maintenance immunosuppressive regimen is unknown, but here are some considerations.

As we think about our patient’s HIV care after transplant, what is the monitoring strategy post-transplantation in the HIV + recipient?

  • HIV RNA and CD4 T cell counts should be measured first 1 mo after transplant and then every 2-3 mo thereafter.
  • The goal here is to trend and see how low these dip / how long it takes. Jennifer explained the importance of counseling patients pre-transplant that their CD4 will likely go down after transplant.  Your patients are likely on top of these numbers and might be alarmed if they don’t know
      • While these might be transient for a liver transplant recipient who receives methylpred induction, this can be more substantial and sustained in those receiving lymph depleting induction.
      • CD4 counts tend to drop closely to the patient’s nadir, so Jennifer likes to figure out their nadir and try to counsel on what she anticipates might happen.  Although can’t plan for everything, giving even some guidance can be helpful.
      • Would add that any treatment for rejection will alter this course

How do you think about the risk of overall and opportunistic infections in the recipient?

The HIV-TR cohort that Jennifer mentioned is from the study linked below and was the first to look at HIV+ transplants.  While patients were not at a higher risk for opportunistic infections (compared to HIV-uninfected counterparts), they were at higher risk for other standard post-operative infections (such as UTI or pneumonia).

 

Opportunistic infection prophylaxis in HIV+ transplant recipients

*Can refer to Table 3 in AST ID COP Guidelines, but ultimately would refer to most up-to-date national HIV guidelines for prophylaxis against OIs*

  • PJP prophylaxis for minimum of 1-year post-transplant is in the guidelines: “The need for extended Pneumocystis prophylaxis beyond 1 year should be weighed against therapy-related adverse effects that may warrant early discontinuation”
      • It is important to note that the HIV-TR protocol called for lifelong PCP prophylaxis, but its not clear that patients need this aggressive approach, particularly depending on where their CD4 count is
      • Some physicians may choose to discontinue use <12 months based on CD4 count as the guide or other factors
  • Toxoplasma prophylaxis if IgG+ recipient with CD4 <100 or any recipient of toxo D+ organ, for one year when using as both PJP and Toxo ppx
  • CMV prophylaxis 
  • MAC prophylaxis might be indicated if CD4 falls below 50
  • Histoplasma or Coccidioides ppx might be indicated in certain endemic areas

Make sure to address vaccination status!

  • Table 4 of AST IDCOP Guidelines as vaccine recommendations

Pearl: Jennifer emphasized attention to HPV

  • This is often not thought about as much in non-HIV patients moving forward with transplant, other than getting yearly pap smears, but HPV can be quite aggressive and difficult to manage post-transplant in these patients
  • In addition to cervical pap smears, don’t forget about anal pap smears in patients where this is indicated.
  • The next key is ensuring that abnormal pap smears are referred for appropriate steps (colposcopy/anoscopy/HRA) prior to transplant.
  • It is valuable to reassure your patients that this is not an effort to preclude them from transplant but is information that is important to know beforehand
  • Checking to get HPV vaccine to patients as well

How do patients with HIV who receive a transplant do?  Do they have similar outcomes to transplant recipients that do NOT have HIV?

In most HIV+ transplant studies, a high rejection rate was surprisingly seen which we don’t completely understand — in excess of 30% in kidney recipients and nearly twice those of HIV-uninfected liver recipients.  

  • It’s important to counsel on concepts and risk of rejection, and to explain that HIV+ patients have higher risk of rejection based on the available data.  Looking forward, Jennifer mentioned that there is ongoing research looking into prevention of rejection, such as a multi-center study looking at maraviroc (CCR5 inhibitor)
  • It’s possible that this rejection was driven by the management of immunosuppression and DDIs (such as CNI + PIs).  Another considered hypothesis is related to immune dysregulation that predisposes the patient to rejection, but we don’t have a clear answer

 

That being said, the overall long-term outcomes of liver and kidney transplant are similar between HIV infected and uninfected recipients (assuming no complications such as stopping medications, etc).

  • Data on outcomes is mostly available from liver and kidney transplants, which are the most common.  There are small case series from other organs, but multi-center or prospective data is lacking.
  • One caveat to this might be patients with HCV+HIV co-infection who receive liver transplants.  Historically, there appeared to be decreased allograft and patient survival compared to HIV mono-infected recipients.  
    • It’s possible though that this was impacted by timing and being prior-DAA.  In the post-DAA era, most places are comfortable with transplants and may have more similar outcomes.


Resources for outcomes data:

A quick word on HIV to HIV transplantation and the HOPE Act!

Episode Art & Infographics

Goals

Listeners will be able to describe the criteria and management of HIV+ individuals undergoing solid organ transplantation. 

Learning Objectives

After listening to this episode, listeners will be able to:

  • List the suggested criteria for solid organ transplantation in HIV-infected candidate
  • Discuss considerations in HIV+ transplant candidates with co-infection with hepatitis B and hepatitis C
  • Analyze HIV antiretroviral regimens in transplant candidates 
  • Describe risk for infectious complications and rejection in HIV+ transplant recipients
  • Identify HIV-to-HIV transplantation as an ongoing area of research

Disclosures

Our guest (Jennifer Husson) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Husson, J., Patel, A., Dong, S. “20: HIV & Solid Organ Transplants”.  Febrile: A Cultured Podcast. https://player.captivate.fm/episode/3208ea2c-1fda-4771-88a0-96685afcc027

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