Abacavir Hypersensitivity Mimicking Infection: Diagnostic Challenges in Two HIV Patients

Background

Abacavir hypersensitivity syndrome (AHS) is a potentially life-threatening adverse drug reaction strongly associated with the HLA-B*57:01 allele ^1,2. While classically presenting with fever, rash, and systemic symptoms, atypical presentations involving liver injury may complicate diagnosis ³. We report two such cases of abacavir hypersensitivity in patients with HIV who were switched from tenofovir-based regimens.

These cases highlight the variable presentation of abacavir hypersensitivity, including cholestatic hepatitis without rash. Rechallenge can precipitate severe reactions, including shock. HLA-B*57:01 screening should be done if feasible in case of HIV patient who presents with hepatitis after initiation of abacavir to prevent morbidity and mortality ^1,4.

Case 1

A 34-year-old woman living with HIV, previously stable on tenofovir/lamivudine/dolutegravir (TLD), was switched to abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) due to transient increase in serum creatinine level. She had no prior history of drug allergy, autoimmune disease, or liver disease. Approximately six weeks after initiating abacavir, she presented with persistent fever, severe right upper quadrant abdominal pain, dark urine, jaundice, malaise, and anorexia. There were no respiratory symptoms or skin rash. On examination, she was febrile, tachycardic, and icteric, with right upper quadrant tenderness. No lymphadenopathy or rash was noted. Laboratory investigations revealed a cholestatic pattern of liver injury, with markedly elevated alkaline phosphatase (ALP), elevated gamma-glutamyl transferase (GGT), hyperbilirubinemia, and mild-to-moderate elevation of transaminases. Infectious workup, including hepatitis A, B, C, E, dengue, malaria, CMV, EBV, and blood cultures, was negative. Autoimmune markers were also negative. Abdominal ultrasound showed no biliary obstruction or structural abnormalities.

During early evaluation, abacavir was unintentionally reintroduced twice :

• First rechallenge: rapid onset of high fever and worsening abdominal pain with further elevation of ALP and bilirubin
• Second rechallenge: fever, tachycardia, and acute hypotension requiring emergency intravenous fluid resuscitation

Symptoms resolved rapidly after discontinuation of abacavir, strongly suggesting abacavir hypersensitivity syndrome (AHS) ^2,5.

Pharmacogenetic testing confirmed HLA-B*57:01 positivity, indicating high risk for AHS ^1.

Abacavir was permanently discontinued. The patient improved with supportive care, and liver function normalized over 2–3 weeks. She was restarted on ART (TAF/FTC/DTG) without recurrence.

Case 2

A 44-year-old man with HIV infection, previously stable on TLD, was switched to an abacavir-based regimen due to rising creatinine levels. Two weeks after initiating abacavir, he presented with fever, chills and RHC pain. On admission, he was hemodynamically stable. Laboratory evaluation showed: GGT: 98 U/L,Total bilirubin: 1.8 mg/dL,AST: 56 U/L, ALT: 65 U/L, Creatinine: normal,Hemoglobin: 11 g/dL, WBC: 11 ×10⁹/L, Platelets: 248 ×10⁹/L,CRP: 75 mg/L,Procalcitonin: 0.12 ng/mL, Chest X-ray and abdominal ultrasound were normal. Significant infectious causes were not identified. Abacavir was discontinued, following which fever subsided and liver enzymes normalized. This clinical course supported a diagnosis of abacavir hypersensitivity ^3,5. A decision was made to switch to an alternative antiretroviral regimen. Pharmacogenetic test for abacavir hypersensitivity HLA-B*5701 was done and result as positive.

Fig. 1: HLA-B*5701 result of case 1

Fig 2: HLA-B*5701 result of case 2

Discussion

Abacavir hypersensitivity syndrome is an immunologically mediated adverse reaction strongly associated with the HLA-B*57:01 allele ^1,2. It typically presents within the first six weeks of therapy and is characterized by fever, malaise, gastrointestinal symptoms, and rash ^2. These two cases highlight several important clinical considerations:

1. Variable Clinical Presentation
   Case 1 demonstrated severe cholestatic hepatitis with systemic involvement, without rash, while Case 2 presented with isolated fever and mild liver enzyme elevation, mimicking infection. Such variability is well documented and may delay diagnosis ^3.
2. Hepatic Involvement
   Although not classically emphasized, liver injury—including cholestatic patterns—can occur in AHS. Previous reports have described hepatotoxicity as part of systemic hypersensitivity reactions ⁶.
3. Rechallenge Risk
   Re-exposure to abacavir is strictly contraindicated. Rechallenge can lead to rapid and more severe reactions, including hypotension and shock, as seen in Case 1 ^2,5.
4. Importance of HLA-B*57:01 Testing
   Screening for HLA-B*57:01 prior to abacavir initiation significantly reduces the risk of AHS and is recommended by WHO and international HIV treatment guidelines ^1,4.
5. Diagnostic Challenges
   Both cases initially mimicked infectious etiologies. Negative investigations and rapid resolution after drug discontinuation were key diagnostic indicators ^3.

Conclusion

Abacavir hypersensitivity syndrome can present with diverse manifestations, including cholestatic hepatitis and isolated febrile illness without rash. Rechallenge may result in life-threatening complications such as shock.

These cases emphasize:

• The crucial role of HLA-B*57:01 screening in case of suspected abacavir hypersensitivity.
• The need for clinical vigilance in patients presenting with fever and liver dysfunction after abacavir initiation.
• The importance of immediate and permanent discontinuation of abacavir.

Early recognition is essential to prevent severe morbidity and mortality.

References

1. Mallal S, Nolan D, Witt C, et al. (2002) Association between presence of HLA-B*5701 and hypersensitivity to abacavir. Lancet.;359(9308):727–732.
2. Hetherington S, McGuirk S, Powell G, et al. (2001) Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir. Clin Ther.;23(10):1603–1614.
3. Phillips EJ, Mallal SA. (2007) Drug hypersensitivity in HIV. Curr Opin Allergy Clin Immunol.;7(4):324–330.
4. World Health Organization. Updated recommendations on HIV prevention, infant diagnosis, antiretroviral initiation and monitoring. Geneva: WHO; 2021.
5. Saag M, Balu R, Phillips E, et al. (2008) High sensitivity of HLA-B*5701 screening for abacavir hypersensitivity. Clin Infect Dis;46(7):1111–1118.
6. Borras-Blasco J, Navarro-Ruiz A, Borras C, Castera E. (2008) Adverse reactions to abacavir: a review of hypersensitivity reactions. J Antimicrob Chemother;62(5):879–885.

Author Information

Aye-Mya-Theingi-Win¹, Khin-Rupar-Ko², Aye-Aye-Win³, May-Zabe⁴, Nyunt Thein⁵

1. Senior Consultant physician, Tropical and Infectious Diseases Department, Yangon General Hospital
2. Professor, Tropical and Infectious Diseases Department, Yangon General Hospital
3. Associated Professor, Tropical and Infectious Diseases Department, University of Medicine (1), Yangon
4. Senior Consultant physician, Former Head of Department of Medicine, Emeritus Professor of Medicine, University of Medicine (1), Yangon