Amaç: HIV tedavisinde Abakavir'in kullanımı için en büyük kontrendikasyonu aşırı duyarlılık reaksiyonudur. Abakavir'e karşı gelişen aşırı duyarlılık reaksiyonu HLA-B57:01 alleli varlığı ile yakın ilişkili olduğu saptanmıştır. Bu çalışmanın yapıldığı tarihlerde ülkemizde bu alanda çok merkezli farklı bir çalışma yapılmamıştı. Bu çalışmada, HIV pozitif yeni tanı almış, henüz tedaviye başlamamış hasta grubundaki HLA-B57:01 allel sıklığının allel spesifik PCR ile taranması amaçlanmıştır. Gereç ve Yöntemler: Retrospektif olan çalışma için Ocak-Aralık 2021 tarihlerinde ''Halk Sağlığı Genel Müdürlüğü, Ulusal HIV-AIDS Doğrulama ve Viral Hepatitler Referans Laboratuvarına'' yeni tanı almış 235 hastaya ait plazma örneklerinden izole edilen DNA örnekleri dâhil edilmiştir. HLA-B57:01 allel sıklığının allel spesifik PCR ile taranması amaçlanmış, pozitif bulunan örnekler için semi-nested PCR yapılmıştır. DNA örneklerinin izlenebilmesi için EDTA 0,5 M, 10XTBE solüsyonları hazırlanmıştır. Verilerin analizi SPSS15 paket programında yapılmıştır. Bulgular: HLA-B57:01 allel varlığı yönünden test edilen toplam 235 örneğin 5'inde (%2,12) allel pozitifliği saptandı. Pozitif bulunan 5 hastanın 35 yaş ve altındaki hasta grubunda olduğu belirlendi. HLA-B57:01 pozitifliği ile cinsiyet arasındaki ilişkide; pozitif hastaların erkek olduğu, tüm erkek hastaların %2,8'inin HLA-B57:01 alleli taşıdığı belirlendi (p=0,371). Coğrafik dağılım değerlendirildiğinde; en sık allel pozitifliği Karadeniz Bölgesinde izlenmiştir. Sonuç: Test edilen örneklerin azlığı sebebiyle, bölgesel temsiliyet sağlanamamıştır. İlerleyen dönemde, tüm bölgeleri temsil edecek düzeyde örneklerin dâhil edildiği, allel varlığı ile birlikte klinik yansımalarının da değerlendirilebileceği, HLA-B57:01 allel ile CD4 Th lenfosit sayısı arasındaki ilişkinin saptanabileceği, aşırı duyarlılık reaksiyonu veya benzeri semptomlarda deri yama testi gibi geniş kapsamlı çalışmaların yapılması gerektiği sonucuna varılmış olup bu çalışmamızın da sonraki çalışmalara ışık tutacağı kanaati oluşmuştur.
Anahtar Kelimeler: HIV; HLA-B57:01 allel pozitif; Abakavir; aşırı duyarlılık sendromu; semi-nested PCR
Objective: The biggest contraindication for the use of Abacavir in HIV treatment is hypersensitivity reaction. Hypersensitivity reactions to abacavir have been found to be closely related to the presence of the HLAB57:01 allele. At the time this study was conducted, no other multicenter study had been conducted in this area in our country. The aim of this study was to screen the frequency of the HLA-B57:01 allele in the patient group newly diagnosed with HIV and not yet started on treatment, using allele-specific PCR. Material and Methods: This retrospective study includes the DNA samples isolated from blood samples which belong to 235 newly diagnosed patients who were sent to ''General Directorate of Public Health, National HIV-AIDS Verification and Viral Hepatitis Reference Laboratories'' between January-December 2021. It was aimed to screen the frequency of the HLA-B57:01allele by allele-specific PCR. EDTA 0.5 M, 10XTBE solutions were prepared to monitor DNA samples. Data analysis was performed using the SPSS 15 software package. Results: Allele positivity was detected in 5 (2.12%) of 235 samples tested for the presence of HLAB57: 01 allele. It was determined that 5 positive patients were in the group of patients aged 35 years and younger. In the relationship between HLA-B57:01 positivity and gender; It was determined that all positive patients were male, and 2.8% of all male patients carried the HLA-B57:01 allele (p=0.371). When evaluating the geographic distribution; allele positivity was most frequently observed in the Black Sea region. Conclusion: Due to the small number of samples tested, regional representation could not be achieved. In the following period, it was concluded that samples representing all regions were included, especially the presence of alleles and the clinical reflections could be evaluated, the relationship between HLA-B57:01 allele and CD4 Th lymphocyte count could be determined, more comprehensive studies such as skin patch tests in hypersensitivity reactions or similar symptoms should be conducted, and it was concluded that this study of ours would shed light on subsequent studies.
Keywords: HIV; HLA-B7:01 allele positive; Abacavir; hypersensitivity syndrome; semi-nested PCR
- Joint United Nations Programme on HIV/AIDS. The urgency of now: AIDS at a crossroads. Geneva: Licence; 2024. [Link]
- Kuritzkes DR, Koup RA. HIV-1: Pathogenesis, Clinical Manifestations, and Treatment. Knipe DM, Howley PM eds. Fields Virology. 6th ed. Philadelphia USA: Wolters Kluwer; 2013.
- Tümer A, Ünal S. Güncel bilgiler ışığında HIV/AIDS. 4. Baskı. Ankara: Bilimsel Tıp Yayınevi; 2016.
- German advisory committee blood (arbeitskreis blut), subgroup 'assessment of pathogens transmissible by blood'. Human Immunodeficiency Virus (HIV). Transfus Med Hemother. 2016;43(3):203-22. [Crossref] [PubMed] [PMC]
- [Link]
- Ryom L, Cotter A, De Miguel R, Béguelin C, Podlekareva D, Arribas JR, et al. 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0. HIV Med. 2020;21(10):617-24. [Crossref] [PubMed] [PMC]
- EACS European AIDS Clinical Society. 2020 Guidelines. Version 12.0. October 2023. [Link]
- Deveci A, Çoban AY, Durupınar B. HIV ile enfekte hastalarda insan lökosit antijeni (HLA)-B*57:01 prevalansı [Prevalence of human leukocyte antigen (HLA)-B*57:01 in HIV-Infected Patients]. Mikrobiyol Bülteni. 2016;51(4):544-51. [Crossref]
- Park I, Terasaki P. Origins of the first HLA specificities. Hum Immunol. 2000;61(3):185-9. [Crossref] [PubMed]
- Poggi H, Vera A, Lagos M, Solari S, Rodríguez P L, Pérez CM. HLA-B*5701 frequency in Chilean HIV-infected patients and in general population. Braz J Infect Dis. 2010;14(5):510-2. [Crossref] [PubMed]
- Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995;267(5197):483-9. [Crossref] [PubMed]
- T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü. HIV/AIDS Tanı Tedavi Rehberi. Ankara: Sağlık Bakanlığı; 2019. [Link]
- World Health Organization [Internet]. © 2024 WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. [Cited: 30.08.2024] Available from: [Link]
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. 2024. [Cited: 30.08.2024] [Link]
- Günthard HF, Calvez V, Paredes R, Pillay D, Shafer RW, Wensing AM, et al. Human immunodeficiency virus drug resistance: 2018 recommendations of the international antiviral society-USA panel. Clin Infect Dis. 2019;68(2):177-87. [Crossref] [PubMed] [PMC]
- WHO HIVResNet HIV drug resistance laboratory operational framework, second edition. Geneva: World Health Organization;. 2020. Licence: CC BY-NC-SA 3.0 IGO. [Link]
- Martin MA, Klein TE, Dong BJ, Pirmohamed M, Haas DW, Kroetz DL; Clinical pharmacogenetics implementation consortium. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther. 2012;91(4):734-8. [Crossref] [PubMed] [PMC]
- Ma JD, Lee KC, Kuo GM. HLA-B*5701 testing to predict abacavir hypersensitivity. PLoS Curr. 2010;2:RRN1203. [Crossref] [PubMed] [PMC]
- Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al.. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 20087;358(6):568-79. [Crossref] [PubMed]
- Saag M, Balu R, Phillips E, Brachman P, Martorell C, Burman W, et al. High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis. 2008;46(7):1111-8. [Crossref] [PubMed]
- Rodríguez-Nóvoa S, García-Gascó P, Blanco F, González-Pardo G, Castellares C, Moreno V, et al. Value of the HLA-B*5701 allele to predict abacavir hypersensitivity in Spaniards. AIDS Res Hum Retroviruses. 2007;23(11):1374-6. [Crossref] [PubMed]
- Martínez Buitrago E, Oñate JM, García-Goez JF, Álvarez J, Lenis W, Sañudo LM, et al.HLA-B*57:01 allele prevalence in treatment-Naïve HIV-infected patients from Colombia. BMC Infect Dis. 2019;19(1):793. [Crossref] [PubMed] [PMC]
- UK Collaborative HIV Cohort Study Steering Committee. HLA B*5701 status, disease progression, and response to antiretroviral therapy. AIDS. 2013;27(16):2587-92. [Crossref]
- Campbell MC, Tishkoff SA. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet. 2008;9:403-33. [Crossref] [PubMed] [PMC]
- Hughes AR, Mosteller M, Bansal AT, Davies K, Haneline SA, Lai EH, et al. Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations. Pharmacogenomics. 2004;5(2):203-11. [Crossref] [PubMed]
- Nolan D, Gaudieri S, Mallal S. Pharmacogenetics: a practical role in predicting antiretroviral drug toxicity? J HIV Ther. 2003;8(2):36-41. [PubMed]
- Orkin C, Wang J, Bergin C, Molina JM, Lazzarin A, Cavassini M, et al. An epidemiologic study to determine the prevalence of the HLA-B*5701 allele among HIV-positive patients in Europe. Pharmacogenet Genomics. 2010;20(5):307-14. [Crossref] [PubMed]
- Young B, Squires K, Patel P, Dejesus E, Bellos N, Berger D, First large, multicenter, open-label study utilizing HLA-B*5701 screening for abacavir hypersensitivity in North America. AIDS. 2008;22(13):1673-5. [Crossref] [PubMed]
- Berka N, Gill JM, Liacini A, O'Bryan T, Khan FM. Human leukocyte antigen (HLA) and pharmacogenetics: screening for HLA-B*57:01 among human immunodeficiency virus-positive patients from southern Alberta. Hum Immunol. 2012;73(2):164-7. [Crossref] [PubMed]
- Cao K, Hollenbach J, Shi X, Shi W, Chopek M, Fernández-Viña MA. Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations. Hum Immunol. 2001;62(9):1009-30. [Crossref] [PubMed]
- Leszczyszyn-Pynka M, Aksak-Wąs B, Urbańska A, Parczewski M. Protective effect of HLA-B*5701 and HLA-C-35 genetic variants in HIV-positive caucasians from northern poland. PLoS One. 2015;10(6):e0127867. [Crossref] [PubMed] [PMC]
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