Abacavir, a nucleoside reverse transcriptase inhibitor, is associated with hypersensitivity reactions (ABC HSR) in 5–8% of white patients infected with HIV-1 [1,2]. Such reactions usually occur within the first 6 weeks of abacavir treatment and are characterized by multisystem involvement [2]. Discontinuing abacavir usually promptly reverses HSR, whereas subsequent rechallenge can cause rapid, severe, and even life-threatening hypotension, renal failure, and/or death [2–4]. A strong association between human leukocyte antigen (HLA) types and occurrence of ABC HSR has been demonstrated in populations mainly consisting of whites [5,6]. In addition, recent studies have shown that routine screening for HLA-B*5701 significantly reduces the incidence of ABC HSR [7–9], and the Prospective Randomized Evaluation of DNA Screening in a Clinical Trial (PREDICT-1) assessment demonstrated a 100% negative predictive value (NPV) for HLA-B*5701 with skin patch-test-confirmed ABC HSR and a 96% NPV with clinically suspected ABC HSR [10]. Here we describe two Taiwanese patients tested negative for HLA-B*5701 who developed febrile agranulocytosis after receiving abacavir. Case 1 A 31-year-old Taiwanese man was diagnosed with HIV-1 infection in 1997 at the age of 23 years. He had poor compliance to antiretroviral therapy and was lost to follow-up until September 2005, when he was admitted after the diagnosis of Pneumocystis jirovecii pneumonia (PJP). His symptoms improved dramatically after receiving a 3-week course of sulfamethoxazole/trimethoprim treatment. Highly active antiretroviral therapy (HAART) was reinitiated with a regimen of efavirenz, lopinavir/ritonavir, stavudine, and abacavir. After 1 week of treatment, the patient suddenly developed fever with a temperature of 38°C accompanied by chills, headache, and generalized maculopapular skin rashes. Blood tests showed a white blood cell count of 700 cells/μl and an absolute neutrophil count of 203 cells/μl. Because of the observed fever and agranulocytosis, ceftazidime was prescribed empirically. Further investigations for the causes of fever proved negative. ABC HSR was suspected, and abacavir was discontinued. The fever, headache, and skin rash were resolved in 2 days, and absolute neutrophil count increased over the following days (Table 1). Host genotyping showed that the patient was HLA-B*5701-negative (HLA-A02, HLA-B380201, HLA-B5101, sample not sufficient for complete HLA typing).Table 1: Laboratory features of patients with abacavir-related agranulocytosis.Case 2 A 36-year-old Taiwanese man infected with HIV-1 started antiretroviral therapy, including nevirapine, abacavir, and lamivudine, in March of 2009. Four weeks later, a dry cough and sore throat developed, though the patient continued antiretroviral therapy. Approximately, 6 weeks after initiation of antiretroviral therapy, the patient developed a fever (39°C), skin rash, headache, oral ulcers, and diarrhea that lasted for 1 week. At presentation, blood tests showed a white blood cell count of 590 cells/μl and an absolute neutrophil count of 30 cells/μl. A complete infectious survey was performed, and under the suspicion of PJP, intravenous sulfamethoxazole/trimethoprim was started. All antiretroviral drugs were discontinued and granulocyte colony stimulating factor was administered. The patient's neutrophil count recovered 2 weeks later (Table 1). A new antiretroviral therapy consisting of lamivudine and zidovudine and atazanavir was prescribed. Subsequent hematological examinations showed normal results. As in case 1, this patient was also tested negative for HLA-B*5701 (HLA-A02, HLA-A11, HLA-B151101, HLA-B550201, HLA-Cw01, HLA-Cw03, HLA-DQB1*03, HLA-DQB1*0401, HLA-DRB1*04, HLA-DRB1*09). A review of the literature identified only three case reports documented abacavir-induced agranulocytosis [11–13]. One of these patients was HLA-B*5701-positive [13], whereas the other two did not undergo genotyping. In our case report, both patients were HLA-B*5701-negative and they clearly developed severe ABC HSR that met all clinical criteria [5]. When encountering such circumstances, there are population-specific aspects that should be taken into consideration. First, recent studies reveal that the frequency of HLA-B*5701 varies among different ethnic populations [14,15]. The only published investigation based on Taiwanese population showed that the frequency of HLA-B*5701 is much lower than that among whites (0.4 vs. 7.3–12.2%) [16]. Including our two patients, only five Taiwanese developing ABC HSR had been reported and all of them were HLA-B*5701-negative. Due to the limited case reports, whether there are specific genes responsible for ABC HSR in the Taiwanese population is unknown. Further studies are warranted. In conclusion, our case report emphasized that a negative HLA-B*5701 genotyping result may not predict the absence of ABC HSR in the Taiwanese populations. Until an ideal screening tool is readily available, appropriate clinical counseling and monitoring in the first 6 weeks of abacavir-containing HAART are necessary when treating nonwhite patients infected with HIV. Acknowledgements S.-J.C., S.-P.Y., and C.-P.F. were responsible for the analysis of the data, reviewing the literature, and writing the article; C.-C.H. was responsible for the confirmation of the HLA typing through sequence-based analysis. All authors have read and approved the final version of the article.