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PATIENT CASES

Case #1

A 46-year-old woman, newly diagnosed with HIV infection, initiated therapy with abacavir, lamivudine and efavirenz. Her HLA-B*5701 status is unknown.

On day 8 of therapy, her physician noted a mild pruritic rash on her neck and trunk.

  • The patient was afebrile, had no gastrointestinal symptoms, and felt well
  • She did not have any muscle or joint aches, respiratory symptoms, or tenderness or swelling of the lymph nodes
  • She had not taken any other medications

Differential diagnoses include:

  • A reaction to efavirenz
  • Abacavir hypersensitivity
  • Immune reconstitution syndrome.

Course of action:

  • Patient has a single mild symptom, so closely monitor for resolution or progression before making a decision:
    • Review symptoms of hypersensitivity
    • Instruct patient to continue all medications and immediately contact physician if other symptoms develop
    • Re-evaluate patient after 24 hours

Follow-up:

  • Patient continued all medications
  • Rash improved over the next 4 days with no further symptoms

Conclusion: patient had a transient efavirenz-related rash (i.e. not a hypersensitivity reaction)

Case #1 – alternative scenario

After noticing the rash 3 days before, the patient discontinued all medications; the rash has since resolved.

Course of action:

  • Permanently discontinue abacavir: Although the reaction may have been an efavirenz rash, by stopping all drugs it is no longer possible to differentially diagnose an abacavir hypersensitivity reaction without exposing the patient to the risk of rechallenge.

Case #1 summary

  • A single symptom is not sufficient for a diagnosis of hypersensitivity
    • Drug interruption after a single symptom should be avoided
      • Resolution of symptom off-drug makes a differential diagnosis impossible
    • However, if abacavir is interrupted, it should not be restarted 
      • Resolution of symptom may represent aborted evolution of a multisymptom hypersensitivity reaction
      • Reinitiation puts the patient at risk for a rechallenge reaction
      • Abacavir should be retrieved from patient to avoid the risk of rechallenge
    • Take a careful history, and review for other symptoms
    • Continue to monitor the patient
    • Avoid corticosteroids in case they mask the development of additional symptoms
    • Use antihistamines if necessary for the patient’s comfort

Case #2

A 29-year-old male with a history of (herpes simplex virus) HSV and syphilis has been newly diagnosed with HIV, low CD4 (<200 cells/mm3), and high viral load.

  • Negative screening result for HLA-B*5701
  • Initiated abacavir, lamivudine and lopinavir/r
  • Concomitant medications:
    • Valacyclovir (chronic medication) initiated before antiretroviral therapy
    • Co-trimoxazole initiated with antiretrovirals

Day 8

Patient noted myalgias and low-grade fever peaking at 37.8°C.

Day 9

Patient noted faint rash with low-grade fever peaking at 39°C approximately 9 hours after morning dose.

Day 10

Patient experienced same symptoms at the same time after morning dose, but fever peaked at 38°C with fewer myalgias.

Day 11

Patient was evaluated in clinic:

  • Temperature 37°C
  • Generalised fine urticarial rash
  • Asymptomatic

Course of action:

  • Symptoms appear to have been resolving each day despite continued abacavir dosing over several days
  • Symptom resolution and the patient’s negative HLA-B*5701 screening status suggest another aetiology
  • Continue abacavir dosing with close monitoring and discontinue co-trimoxazole

Follow-up:

  • Co-trimoxazole is stopped on day 11; subject is seen in the clinic on days 12 and 13, and symptoms continue to decline in severity
  • Patient is given topical steroids and antihistamines for the rash
  • By day 15, rash and myalgias have resolved and patient remains afebrile on abacavir, lamivudine, and lopinavir/r

Conclusion: Hypersensitivity to Co-trimoxazole

Case #2 – alternative scenario

Patient is seen on days 12 and 13; symptoms continue but do not increase or decrease in severity.

Patient is given topical steroids and antihistamines for the rash.

By day 15, rash is resolving but myalgias continue; patient complains of malaise.

Course of action:

Permanently discontinue abacavir if no other cause of the patient’s symptoms is identified; in this case, abacavir hypersensitivity cannot be definitively ruled out.

Case #2 summary

  • Consider other causes for rash and fever when patient is taking concurrent medications known to be associated with these symptoms or with allergies, particularly if screening suggests a low risk of abacavir hypersensitivity
  • However, a negative HLA-B*5701 screen does not definitively rule out the possibility of a hypersensitivity reaction
    • If a diagnosis of abacavir hypersensitivity cannot be excluded, then abacavir must be permanently discontinued, regardless of the results of any test

Case #3

45-year-old male initiated treatment with abacavir, lamivudine and boosted fosamprenavir.

HLA-B*5701 status unknown.

Day 5

Onset of vomiting.

Day 6

Onset of diarrhoea; nausea worsens with more frequent vomiting.

Day 7

Development of fever to 39°C and general weakness; gastrointestinal symptoms continue without further increase in severity; careful search revealed no rash.

Course of action:

  • Permanently discontinue abacavir
    • Cumulative, multiorgan symptomatic onset indicates a high probability of a developing abacavir hypersensitivity reaction

Follow-up:

  • Within 24 hours of abacavir discontinuation, patient is afebrile and gastrointestinal symptoms are resolving

Conclusion: Patient experienced abacavir hypersensitivity

Case #3 summary

  • Rash is very common in abacavir hypersensitivity; however, just as rash alone would not be sufficient for a diagnosis of a hypersensitivity reaction, neither is the absence of rash a reason to exclude a diagnosis of hypersensitivity in the presence of other consistent symptoms; rash may occur late or even after discontinuation of abacavir
  • Other features point towards the diagnosis of a hypersensitivity syndrome
  • Patient developed multiorgan involvement, including constitutional and gastrointestinal symptoms
    • Even in the absence of a rash, patient’s symptoms point to a possible diagnosis of abacavir hypersensitivity
  • Symptoms did not all appear at once but in a stepwise manner

Case #4

A 40-year-old woman, initiated abacavir, lamivudine, dolutegravir. The therapy was started before the HLA-B*5701 result was received.

Within a few days of starting therapy, the patient experienced dyspnoea, vomiting and rash.

  • The patient was identified as being HLA-B*5701 positive in medical records (2010 HLA-B*5701 assay result) but it had remained unnoticed by the physician when prescribing the therapy.
  • Treatment with abacavir, lamivudine, dolutegravir was discontinued and the events resolved.
  • Previously administered products included abacavir, lamivudine which had been discontinued due to suspected HSR.

Conclusion: Patient experienced abacavir hypersensitivity

Case #4 summary

  • The abacavir containing product should not have been started prior to receiving the test result. In this example a previous test result was not noticed either, which would have alerted the prescriber to the previous HLA-B*5701 positive status.
  • Abacavir should never be initiated in patients with a positive HLA-B*5701 status.
  • After stopping abacavir for a suspected HSR, any product containing abacavir must never be re-initiated.
  • Restarting abacavir following a suspected HSR can result in a return of symptoms within hours which is more severe than on initial presentation and may include life-threatening hypotension and death.

Case #5

A 50 year old male who was HLA-B*5701 negative, initiated abacavir, lamivudine.

Less than a day after starting abacavir, lamivudine, the patient experienced hypotension, rash and vomiting.

  • The treating physician considered that the rash on initial exposure could be due to co-suspect product efavirenz. Both efavirenz and abacavir, lamivudine were interrupted.
  • The patient was rechallenged with abacavir, lamivudine and within hours experienced vomiting and severe hypotension, which was considered life threatening and resulted in hospitalisation.
  • Treatment with abacavir, lamivudine was permanently discontinued and the patient recovered.

Conclusion: The patient experienced abacavir hypersensitivity

Case #5 summary

  • HLA-B*5701 is not always present in people who have a suspected abacavir HSR. Clinical diagnosis of suspected HSR to abacavir remains the basis for clinical decision making.
  • HLA-B*5701 testing should never be a substituted for clinical vigilance/ judgement and patient management.
  • Restarting abacavir following a suspected HSR, even in the absence of the HLA-B*5701 allele, can result in a return of symptoms within hours which is more severe than on initial presentation and may include life-threatening hypotension and death.

NP-GBL-HVX-WCNT-220048 November 2022

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