year 16, Issue 1 (January - February 2022)                   Iran J Med Microbiol 2022, 16(1): 66-75 | Back to browse issues page


XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Dolati F, Behboudi E, Naderi M, Shahramian I, Moradi A. Evaluation of Lamivudine Resistance Mutations in HBV/HIV Co-infected Patients. Iran J Med Microbiol. 2022; 16 (1) :66-75
URL: http://ijmm.ir/article-1-1530-en.html
1- Department of Microbiology, Damqan Azad University, Damqan, Iran
2- Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran
3- Infectious Disease Research Center, Golestan University of Medical Sciences, Gorgan, Iran
4- Department of Pediatric, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
5- Department of Microbiology, Golestan University of Medical Sciences, Gorgan, Iran , abmoradi@gmail.com
Abstract:   (1064 Views)

Background and Objective: The drug resistance mutations are key elements in the failure of long-term treatment of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. The mutation in the YMDD motif in the P gene of HBV is the most critical factor in antiviral drug (especially lamivudine) resistance. This study aimed to assess the YMDD motif and other polymerase gene mutations in individuals with HBV/HIV coinfection.
Materials and Methods: All enrolled patients were under lamivudine treatment. Blood samples were collected from 37 HBV/HIV-positive patients, and DNA was extracted. The P gene was amplified by the PCR method with appropriate primers. The PCR products for detecting mutations in the P gene were sent to the Macrogen. To investigate the P gene mutations, the obtained sequences were compared with the polymerase gene of the HBV standard sequence in the GeneBank (accession number AB033559).
Results: The mean age of the patients was 34.1±5.7 years, of which 59.5% were male, and 40.5% were female. Of all patients, 56% were drug abusers, 35% had risky sexual behavior, 56% had prison history, and 33% had addicted wives. The 37 extracted samples were sequenced successfully. Among the studied samples (n =37), 28 patients had simultaneous mutations of YIDD and FLMAQ, 1 patient had YINN and FLIPH and 1 patient had YIDD and FSLAQ.
Conclusion: In summary, drug-resistant variants were detectable in most coinfected patients with chronic Hepatitis B (CHB) and HIV. As a result of mutations, therapeutic strategies sometimes are not effective. Therefore, recognition and monitoring of drug resistance mutations are critical.

Full-Text [PDF 1307 kb]   (203 Downloads) |   |   Full-Text (HTML)  (821 Views)  
Type of Study: Original Research Article | Subject: Medical Virology
Received: 2021/10/26 | Accepted: 2021/12/11 | ePublished: 2022/01/20

References
1. Ribeiro CRA, de Almeida NAA, Martinelli KG, et al. Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients. Virol J. 2021;18(1):15. Published 2021 Jan 12. [DOI:10.1186/s12985-021-01487-2] [PMID] [PMCID]
2. Ireland G, Simmons R, Balogun K, Kirwan P, Sabin CA, Ramsay M, et al. HIV coinfection among persons diagnosed with hepatitis B in England in 2008-2014. HIV Med. 2019. [DOI:10.1111/hiv.12707] [PMID]
3. Soriano V, Puoti M, Bonacini M, Brook G, Cargnel A, Rockstroh J, Thio C, Benhamou Y. Care of patients with chronic hepatitis B and HIV coinfection: recommendations from an HIV-HBV International Panel. Aids 2005; 18;19(3):221-40. [DOI:10.1097/01.aids.0000163948.62176.e7]
4. Rajbhandari R, Jun T, Khalili H, Chung RT, Ananthakrishnan AN. HBV/HIV coinfection is associated with poorer outcomes in hospitalized patients with HBV or HIV. J viral hepatitis 2016; 23(10):820-9. [DOI:10.1111/jvh.12555] [PMID] [PMCID]
5. Hanazaki K. Antiviral therapy for chronic hepatitis B: a review; JCDT-I, Allergy 2004; 3(1):63-70. [DOI:10.2174/1568010043483908] [PMID]
6. Lavanchy D, Kane M. Global epidemiology of hepatitis B virus infection. Hepatitis B virus in human diseases. Hepatitis B Virus in Human Diseases Springer. 2016; p. 187-203. [DOI:10.1007/978-3-319-22330-8_9]
7. Maucort‐Boulch D, de Martel C, Franceschi S, Plummer MJIjoc. Fraction and incidence of liver cancer attributable to hepatitis B and C viruses worldwide. J Cancer. 2018;142(12):2471-7. [DOI:10.1002/ijc.31280] [PMID]
8. Lai CL, Dienstag J, Schiff E, Leung NW, Atkins M, Hunt C, Brown N, Woessner M, Boehme R, Condreay L. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis. 2003; 15;36(6):687-96. [DOI:10.1086/368083] [PMID]
9. Alter H, Block T, Brown N, Brownstein A, Brosgart C, Chang KM, et al. A research agenda for curing chronic hepatitis B virus infection. Hepatology. 2018; 67(3):1127-31. [DOI:10.1002/hep.29509] [PMID] [PMCID]
10. Pappoe, F., Hagan, C.K.O., Obiri-Yeboah, D. Sero-prevalence of hepatitis B and C viral infections in Ghanaian HIV-positive cohort: a consideration for their health care. BMC Infect. Dis 2019; 19:380. [DOI:10.1186/s12879-019-4027-y] [PMID] [PMCID]
11. Liaw Y-F, Sung JJ, Chow WC, Farrell G, Lee C-Z, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004; 351(15):1521-31. [DOI:10.1056/NEJMoa033364] [PMID]
12. Feng B, Wei L, Chen M, Wang LJMr. Dynamic changes of hepatitis B virus polymerase gene including YMDD motif in lamivudine-treated patients with chronic hepatitis B. Microbiol Res. 2018; 163(4):487-92. [DOI:10.1016/j.micres.2006.11.004] [PMID]
13. Liu KZ, Hou W, Zumbika E, Ni Q. Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy. J Zhejiang Uni SCI. 2005; 6(12):1182-7. [DOI:10.1631/jzus.2005.B1182] [PMID] [PMCID]
14. Bennet JE, Blaser MJ, Dolin R. Principles and practice of infectious diseases: Elsevier Saunders 2015.
15. Lee CZ, Lee HS, Huang GT, Yang PM, Sheu JC. Detection of YMDD mutation using mutant-specific primers in chronic hepatitis B patients before and after lamivudine treatment. World J Gastroenterol. 2006;12:5301-5. [DOI:10.3748/wjg.v12.i33.5301] [PMID] [PMCID]
16. Karami C, H Adli A, Zhand S, Tabarraei A, Talei R, Saeidi M, Moradi A. Study of Genotype, Subtype and Mutation in the S Gene in Hepatitis B Patients Co-infected with HIV in Iran. Jundishapur J Microbiol 2016; 9(12):e34009. doi: 10.5812/jjm.34009. [DOI:10.5812/jjm.34009]
17. Kobayashi S, Ide T, Sata MJJoh. Detection of YMDD motif mutations in some lamivudine-untreated asymptomatic hepatitis B virus carriers. J. hepatology 2011; 34(4):584-6. [DOI:10.1016/S0168-8278(00)00023-4]
18. Zhang X, Zhang Y, Sun L, Wen Q, Zhou L, Fan G, et al. Study of gene chips in the detection of YMDD mutations in the region of HBV polymeras. Zhonghua yi xue za zhi. 2003; 83(6):459-62.
19. Yan M, Zhang C, Ling Q, Zhou RF. Detection of YMDD motif mutations in lamivudine-untreated patients with chronic hepatitis B. Zhonghua gan zang bing za zhi. 2013;11(7):430-1.
20. Cuestas ML, Mathet VL, Oubiña JR, Sosnik AJPr. Drug delivery systems and liver targeting for the improved pharmacotherapy of the hepatitis B virus (HBV) infection. Pharm Res. 2010; 27(7):1184-202. [DOI:10.1007/s11095-010-0112-z] [PMID]
21. Lin C, Tsai S, Lee T-H, Chien R, Liao S, Liaw YJG. High frequency of functional anti-YMDD and-mutant cytotoxic T lymphocytes after in vitro expansion correlates with successful response to lamivudine therapy for chronic hepatitis B. Gut. 2015; 54(1):152-61. [DOI:10.1136/gut.2003.032920] [PMID] [PMCID]
22. Kobayashi M, Suzuki F, Akuta N, Yatsuji H, Hosaka T, Sezaki H, et al. Correlation of YMDD mutation and breakthrough hepatitis with hepatitis B virus DNA and serum ALT during lamivudine treatment. Hepatology Res. 2010; 40(2):125-34. [DOI:10.1111/j.1872-034X.2009.00565.x] [PMID]
23. Zoulim F, Poynard T, Degos F, Slama A, El Hasnaoui A, Blin P, et al. A prospective study of the evolution of lamivudine resistance mutations in patients with chronic hepatitis B treated with lamivudine. J Viral Hepatitis. 2006; 13(4):278-88. [DOI:10.1111/j.1365-2893.2005.00712.x] [PMID] [PMCID]
24. Gholamreza R, Shahryar S, Abbasali K, Hamidreza J, Abdolvahab M, Khodaberdi K, et al. Seroprevalence of hepatitis B virus and its coinfection with hepatitis D virus and hepatitis C virus in Iranian adult population. Indian J Med Sci. 2017; 61(5):263-8. [DOI:10.4103/0019-5359.32092] [PMID]
25. Lo CM, Liu CL, Lau GK, Chan SC, Ng IO, Fan ST. Liver transplantation for chronic hepatitis B with lamivudine‐resistant YMDD mutant using add‐on adefovir dipivoxil plus lamivudine. Liver Transplant. 2015;11(7):807-13. [DOI:10.1002/lt.20416] [PMID]
26. Inoue J, Ueno Y, Wakui Y, Niitsuma H, Fukushima K, Yamagiwa Y, et al. Four‐year study of lamivudine and adefovir combination therapy in lamivudine‐resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern. J Viral Hepatitis. 2011;18(3):206-15. [DOI:10.1111/j.1365-2893.2010.01301.x] [PMID]
27. Bozdayi A, Uzunalimoǧlu Ö, Türkyilmaz A, Cinar K, Sezgin O, Bozkaya H, et al. A new mutation pattern (YMDD→ YSDD) in YMDD motif of HBV DNA polymerase gene in chronic B hepatitis infection resistant to lamivudine treatment. J Hepatology. 2001; 34:162. https://doi.org/10.1016/S0168-8278(01)80594-8 [DOI:10.1016/S0168-8278(01)81469-0]
28. Delaney IV WE, Locarnini S, Shaw TJAC, Chemotherapy. Resistance of hepatitis B virus to antiviral drugs: current aspects and directions for future investigation. Antivir Chem Chemother. 2011; 12(1):1-35. [DOI:10.1177/095632020101200101] [PMID]
29. Yıldız O, Aygen B, Demirtürk N, Demirdal T, Inan D, Yıldırmak T, et al. Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D. World J Gastroenterol. 2011; 17(45):4987. [DOI:10.3748/wjg.v17.i45.4987] [PMID] [PMCID]
30. Arrese E, Basaras M, Blanco S, Ruiz P, Cisterna R. Evolution of hepatitis B virus during long-term therapy in patients with chronic hepatitis B Ann Hepatol. 2011;10(4), 434-440. [DOI:10.1016/S1665-2681(19)31509-1]
31. Kim J-K, Lee H-J, Lee Y-J, Chun J-Y, Lee I-K, Lim Y-S, et al. Direct detection of lamivudine-resistant hepatitis B virus mutants by a multiplex PCR using dual-priming oligonucleotide primers. J Virol Methods. 2018;149(1):76-84. [DOI:10.1016/j.jviromet.2008.01.003] [PMID]
32. Tamandjou Tchuem CR, Brandt L, Nel EDlR, Cotton MF, Matthews P, Kaindjee-Tjituka F, et al. Hepatitis B virus drug resistance mutations in HIV/HBV coinfected children in Windhoek, Namibia. PLoS ONE. 2020; 15(9): e0238839. [DOI:10.1371/journal.pone.0238839] [PMID] [PMCID]
33. Wang C, Yu S, Zhang Y, Zhang M, Lv L, Huang C, et al. Viral quasispecies of hepatitis B virus in patients with YMDD mutation and lamivudine resistance may not predict the efficacy of lamivudine/adefovir rescue therapy. Exp Ther Med. 2019;17(4):2473-84. [DOI:10.3892/etm.2019.7255] [PMID] [PMCID]
34. Horgan M, Brannigan E, Crowley B, Levis J, Fanning LJ. Hepatitis B genotype and YMDD profiles in an untreated Irish population. J Clin Virol. 2016; 35(2):203. [DOI:10.1016/j.jcv.2005.08.004] [PMID]
35. Thio CL, Locarnini SJAr. Treatment of HIV/HBV coinfection: clinical and virologic issues. AIDS Rev. 2017; 9(1):40-53.
36. Mirandola S, Campagnolo D, Bortoletto G, Franceschini L, Marcolongo M, Alberti A. Large‐scale survey of naturally occurring HBV polymerase mutations associated with anti‐HBV drug resistance in untreated patients with chronic hepatitis B. J Viral Hepatitis. 2011;18(7):e212-e6. [DOI:10.1111/j.1365-2893.2011.01435.x] [PMID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2022 CC BY-NC 4.0 | Iranian Journal of Medical Microbiology

Designed & Developed by : Yektaweb | Publisher: Farname Inc