Panagopoulos P, Paraskevis D, Katsarolis I, Sypsa V, Detsika M, Protopapas K, Antoniadou A, Papadopoulos A, Petrikkos G, Hatzakis A
4th Department of Internal Medicine, ATTIKON University General Hospital, Haidari Athens, Greece 2nd Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
Hygiene and Epidemiology Department, Medical School, University of Athens, Greece.
Int J STD AIDS. 2014 Oct;25(12):860-5. doi: 10.1177/0956462414523259. Epub 2014 Feb 10.
Hyperbilirubinaemia with or without jaundice is one of the side effects of atazanavir boosted with low-dose ritonavir (ATV/rit) related to the drug plasma levels, as a result of its metabolism by UGT1A1 - uridine diphosphate-glucuronosyl transferase. Genotyping for UGT1A128 before initiation of antiretroviral therapy containing atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Our objective was to estimate the prevalence of the UGTA1A128 polymorphism in HIV-infected individuals in Greece and to determine its potential association with hyperbilirubinaemia in patients receiving ATV/rit. The prevalence of the UGTA1A128 variant was estimated in 79 HIV-infected patients prior to the administration of the first-line treatment. The UGTA1A128 variant was detected in 46 out of 79 individuals (58.2%). Antiretroviral therapy was administered to 64/79 patients (81%). Among them, 26/64 (40.6%) received ATV/rit. Of the ATV/rit-treated patients, 14 were found to be carriers of the UGT1A1*28 variant (54%), and maximum serum bilirubin levels were significantly higher in the carrier population (4.71 vs. 2.69 mg/dL, p = 0.026). In 50% of the population, maximum levels were recorded in the first month of follow-up. Although carriage of UGT1A1 is linked with the development of hyperbilirubinaemia, the implementation of a pharmacogenomic approach in clinical practice cannot yet be recommended as a standard of care.
无论有无黄疸，高胆红素血症都是低剂量利托那韦增强的阿扎那韦（ATV/rit）的副作用之一，这与药物血浆水平有关，是其通过UGT1A1（尿苷二磷酸葡萄糖醛酸基转移酶）代谢的结果。在开始含阿扎那韦的抗逆转录病毒治疗前对UGT1A128进行基因分型，可能有助于识别有高胆红素血症风险的个体。我们的目的是估计希腊HIV感染个体中UGTA1A128多态性的患病率，并确定其与接受ATV/rit治疗患者高胆红素血症的潜在关联。在79例HIV感染患者接受一线治疗前，估计UGTA1A128变异体的患病率。79例个体中有46例（58.2%）检测到UGTA1A128变异体。64/79例患者（81%）接受了抗逆转录病毒治疗。其中，26/64例（40.6%）接受了ATV/rit治疗。在接受ATV/rit治疗的患者中，14例被发现是UGT1A1*28变异体的携带者（54%），携带者群体的最大血清胆红素水平显著更高（4.71 vs. 2.69mg/dL，p = 0.026）。在50%的人群中，最大水平出现在随访的第一个月。虽然UGT1A1的携带与高胆红素血症的发生有关，但目前还不能推荐在临床实践中采用药物基因组学方法作为标准治疗。
