A severe hypersensitivity reaction to abacavir following re-challenge

Introduction

Abacavir is a guanosine nucleoside analogue with good activity against HIV. In pre-marketing drug trials, there were reports of a hypersensitivity reaction syndrome associated with significant morbidity. ¹ Hypersensitivity presents with a combination of symptoms such as fever, rash, gastrointestinal disturbance and other systemic symptoms and should be immediately discontinued in a patient if suspected. Re-challenge following discontinuation is absolutely contraindicated due to the severity of clinical syndrome. There are rare reports of mortality with failure to recognise this syndrome as drug hypersensitivity.

Abacavir hypersensitivity is restricted by the Human Leukocyte Antigen (HLA) allele HLA-B*57:01. The incidence of hypersensitivity is calculated at 8%, and HLA testing reduces this risk to 3%. ² Abacavir should not be prescribed to anyone who tests HLA-B*57:01 positive. We report this case to highlight a potentially life-threatening reaction on abacavir re-challenge. Medication is prescribed to an individual, and sharing is to be strongly discouraged.

Case report

A 32-year-old man with HIV-1 infection and positive HLA allele HLA-B*57:01 was commenced on Truvada (tenofovir and emtricitabine), Darunavir 800 mg and Ritonavir 100 mg once daily following diagnosis (January 2015). His baseline CD4 cell count was 510 × 10⁶L⁻¹ (26%) and HIV RNA viral load 16,182 copies/mL. Resistance profile showed no major mutations. He was switched to Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) for simplification when his viral load was <70 copies/mL. He had no significant medical history, no other regular medication and had no allergies. He lived with his HIV-positive partner who was virologically suppressed on Triumeq (abacavir, lamivudine and dolutegravir).

In January 2016, he presented to Accident and Emergency with acute onset widespread rash, fever, chest tightness, shortness of breath, pleuritic like chest pain, frontal headache and vomiting. On examination, he had a widespread maculopapular rash on his torso. He was tachycardiac (122 beats per minute), pyrexic (39°C), tachypnoeic (22 breaths/min) and hypotensive (82/50 mmHg). Oxygen saturations dropped to 88% on room air. Auscultation of his chest was normal. Inflammatory markers (white cell count, c-reactive protein) and chest X-ray were normal. Blood cultures and urinalysis found no infection. An electrocardiogram showed sinus tachycardia (133 beats per minute). He was treated with broad spectrum IV Tazocin (piperacillin and tazobactam) for presumptive chest infection. Six hours later, he remained hypotensive, tachycardiac and pyrexic (>38°C). A computed tomography pulmonary angiogram showed minimal bilateral pleural effusions. His symptoms and signs settled within 24 h. He was prescribed his regular anti-retroviral medication Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) and denied any other medication.

Case note review revealed he had insufficient supply of Stribild, not attended his last outpatient clinic review and admitted to borrowing his partner’s Triumeq (abacavir, lamivudine and dolutegravir). Triumeq had been taken for seven days three months previously and one day prior to this presentation.

Discussion

Abacavir hypersensitivity reaction (AHR) presents with a combination of symptoms including fever, malaise, headache and gastrointestinal symptoms. ³ The median time of onset to symptoms is seven to eight days; however, symptoms have been reported within hours following re-challenge. ⁴ Signs can include hypotension and tachycardia and are more common on re-challenge. Symptoms usually promptly resolve following drug discontinuation; however, re-challenge can result in a more rapid, severe and potentially life-threatening reaction.^3,5–7

As the number of people living with HIV increases, the use of newer combination tablets means patients may not realise what drugs are in the tablet. If couples share tablets, this may increase the number of AHRs in HLA-positive patients which may go unrecognised and carries a higher risk of mortality.

This case illustrates the importance of highlighting to patients with a positive HLA-B*57:01 the meaning of this and explaining which medications are therefore excluded. Counselling patients on risks involved with sharing other patient’s medication should be discussed to avoid future morbidity and mortality. Patients should be provided with literature concerning the practices of medication sharing, side effects and risks involved with sharing medication. Following this case report, we are developing an HLA-B*57:01-positive information leaflet which will emphasise these risks to avoid further similar cases.