A 43-year-old man comes to the office after a recent hospitalization for Pneumocystis pneumonia. The patient is taking trimethoprim-sulfamethoxazole and says that his pulmonary symptoms are better. He has a history of HIV and was on highly active antiretroviral therapy until self-discontinuing treatment 2 years ago. On physical examination, the patient appears to be in no acute distress. BMI is 20 kg/m². A few crackles are heard at the lung bases. His most recent CD4 count is 122/mm³. After discussing medical compliance and the need to resume antiretroviral therapy, HIV genotyping assay is performed. Additional testing for HLA-B*57:01 yields positive results. Which of the following medications is contraindicated in this patient due to the risk of a potentially fatal hypersensitivity reaction?

Question

Quizplus · Accepted Answer

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV/AIDS. Allergic responses can occur with many HIV/AIDS medications. Abacavir hypersensitivity reaction (AHR) is an allergic reaction that develops in 2%-8% of patients and is strongly associated with the HLA-B*57:01 allele of the human leukocyte antigen (HLA) system. AHR occurs due to direct binding of abacavir to a segment on the HLA-B*57:01 molecule, which alters the presentation of self-peptides to the immune system and results in a delayed hypersensitivity reaction (type IV). Manifestations are mediated by a cytotoxic T-cell response and typically include fever, malaise, gastrointestinal symptoms, and a delayed rash. Abacavir discontinuation results in rapid improvement. A negative test for the HLA-B*57:01 allele has almost a 100% negative predictive value for AHR. Therefore, genetic testing is usually done prior to administering the medication. (Choice B) Common side effects of protease inhibitors such as darunavir include metabolic abnormalities (hyperglycemia), gastrointestinal symptoms, and lipodystrophy. (Choices C and E) The non-NRTIs efavirenz and nevirapine may cause Stevens-Johnson syndrome and toxic epidermal necrolysis, but these conditions are not associated with HLA alleles. Liver function abnormalities can also occur with these 2 non-NRTIs. (Choice D) Emtricitabine, another NRTI, has been associated with an asymptomatic macular rash on the palms or soles; no genetic basis for this reaction has been identified. Educational objective: Abacavir hypersensitivity reaction occurs in 2%-8% of patients and is strongly associated with the HLA-B*57:01 allele. __________ References: Abacavir pharmacogenetics-from initial reports to standard of care. (http://www.ncbi.nlm.nih.gov/pubmed/23649914) Hypersensitivity reactions to HIV therapy. (http://www.ncbi.nlm.nih.gov/pubmed/21480946)

A 43-Year-Old Man Comes to the Office After a Recent