EFFECT OF ANTIRETROVIRAL TREATMENT REGIMENS ON LIVER ENZYMES IN HUMAN IMMUNODEFICIENCY VIRUS PATIENTS

  • Adiga Sachidananda Mn Department of Pharmacology, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore - 575 018, Karnataka, India.
  • Adiga Usha S Department of Biochemistry, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore - 575 018, Karnataka, India.

Abstract

Objective: Treatment of human immunodeficiency virus (HIV) with highly active antiretroviral therapy is complicated due to its effect on liver enzymes along with associated risk of opportunistic infection and its treatment. The objective of the study was to compare the effect of two zidovudine and lamivudine-based regimens on liver enzymes and to correlate them with age and CD4 count in HIV patients.

Methods: In this retrospective study, patients who have received zidovudine+lamivudine+nevirapine (ZLN) or zidovudine+lamivudine+efavirenz (ZLE) at least for 1 year were included. Baseline, 6-month, and 1-year values of aspartate amino transferase (AST), alanine amino transferase (ALT), and CD4 count were collected. One-way analysis of variance and unpaired t-test were used to compare the difference in AST, ALT, and CD4 count value within basal, 6 months, and 1 year of two group and between the groups, respectively. Pearson’s correlation was used for correlation study.

Results: Elevation of AST levels in patients who had received ZLN regimen at different interval was significant statistically. There was a statistically significant elevation of ALT level at 6 months. There was no significant change in AST and ALT values in patients who had received ZLE regimen. Between the two regimens, there was statistically significant difference in AST and ALT values at 6 months and 1 year. There was no correlation between age and CD4 count with liver enzymes.

Conclusion: We conclude from the study that nevirapine containing zidovudine regimen showed a slight elevation in AST. The efavirenz regimen did not show a change in AST and ALT.

Keywords: Antiretroviral therapy, Alanine transaminase, Aspartate transaminase, CD4 count.

Author Biographies

Adiga Sachidananda Mn, Department of Pharmacology, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore - 575 018, Karnataka, India.

Professor, Biochemistry,K.S.Hegde Medical Academy,

Deralakatte, Mangalore, Karnataka 575018

Adiga Usha S, Department of Biochemistry, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore - 575 018, Karnataka, India.

Professor, Department of Pharmacology,

K.S.Hegde Medical Academy, Deralakatte, Mangalore,

Karnataka, India 575018

References

1. Nunez MJ, Martin CL, Moreno V, Valencia E, Garcia SJ, Gonzalez CJ. Impact of antiretroviral treatment related toxicities on hospital admissions in HIV infected patients. AIDS Res Human Retrovirus 2006;22:825-9.
2. Palella F, Baker R, Moorman A, Chmiel J, Wood K, Brooks J. Mortality in the highly active antiretroviral therapy era: Changing causes of death and disease in the HIV outpatient study. J Acqui Immune Deficiency Syndrome 2006;43:27-34.
3. Hernandez L, Gilson I, Jacobson J, Affi A, Puetz T, Dindzans V. Antiretroviral hepatotoxicity in HIV-infected patients. Alimen Pharmacol Ther 2001;15:1627-32.
4. den Brinkera M, Ferdinand WN, Pauline ME, van Dillenb W, Suzanne J, Weelb J, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV- infection. AIDS 2000;14:2895-902.
5. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 2000;342:1266-71.
6. Gopal DV, Rosen HR. Abnormal findings on liver function tests. Postgrad Med 2000;107:100-14.
7. Jain MK. Drug induced liver injury associated with HIV medications. Clin Liver Dis 2007;1:615-39.
8. Walker UA. Antiretroviral therapy induced liver alterations. Curr Opin HIV AIDS 2007;2:293-8.
9. Vogel M, Rockstroh J. Hepatotoxicity and liver disease in the context of HIV therapy. Curr Opin HIV AIDS 2007;2:306-13.
10. Mocroft A, Phillips AN, Soriano V, Ledergerber B, Kirk O, Vinogradova E, et al. Euro SIDA StudyGroup: Reasons for stopping antiretroviral regimen: Increased incidence of stopping due to toxicity or patient/physician choice in patients with hepatitis C coinfection. AIDS Res Hum Retroviruses 2005;21:743-52.
11. Curtis LC. HIV antiretroviral medications and hepatotoxicity. Curr Opin HIV AIDS 2007;2:466-73.
12. Pol S, Lebray P, Vallet PA. HIV infection and hepatic enzyme abnormalities: Intricacies of the pathogenic mechanisms. Clin Infect Dis 2004;38:S65-72.
13. Cote HC, Brumme ZL, Craib KJ, Alexander CS, Wynhoven B, Ting L, et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N Engl J Med 2002;346:811-20.
14. Miro O, López S, Martínez E, Pedrol E, Milinkovic A, Deig E, et al. Mitochondrial effects of HIV infection on the peripheral blood mononuclear cells of HIV-infected patients who were never treated with antiretrovirals. Clin Infect Dis 2004;39:710-6.
15. Casula M, Bosboom-Dobbelaer I, Smolders K, Otto S, Bakker M, d Baar MP, et al. Infection with HIV-1 induces adecrease in mt-DNA. J Infect Dis 2005;191:1468-71.
16. Jacotot E, Ravagnan L, Loeffler M, Ferri KF, Vieira HL, Zamzami N, et al. The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med 2000;191:33 46.
17. Balasubramanian A, Koziel M, Groopman JE, Ganju RK. Molecular mechanism of hepatic injury in coinfection with hepatitis C virus and HIV. Clin Infect Dis 2005;41:S32-7.
18. Gross A, Jockel J, Wei MC, Korsmeyer SJ. Enforced dimerization of Bax results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J 1998;17:3878-85.
19. Guaraldi G, Squillace N, Stentarelli C, Orlando G, D’Amico R, Ligabue G, et al. Nonalcoholic fatty liver disease in HIV infected-patients referred to a metabolicclinic: Prevalence, characteristics, and predictors. Clin Infect Dis 2008;47:250-7.
20. Zechini B, Pasquazzi Z, Aceti A. Correlation of serum aminotransferases with HCV RNA levels and histological findingsin patients with chronic hepatitis C: The role of serum aspartate transaminase in the evaluation of disease progression. Eur J Gastroenterol Hepatol 2004;16:891-6.
21. Shakil A, Kramer D, Mazariegos G, Fung JJ, Rakela J. Acute liver failure: Clinical features, outcome analysis, and applicability of prognostic criteria. Liver Transpl 2000;6:163-9.
22. Zimmerman H. Drug-induced liver disease. In: Schiff E, Sorrell W, Muldrey W, editors. Schiff’s Diseases of the Liver. 8th ed. Philadelphia: Lippincott-Raven Publishers; 1999. p. 973-1064.
23. Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RD. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: Role of hepatitis C and B infections. Hepatology 2002;35:182-9.
24. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Elevated liver enzymes following initiationof antiretroviral therapy. JAMA 2000;19:2526-7.
25. Lana R, Nunez M, Mendoza JL, Soriano V. Rate and risk factors of liver toxicity in patientsreceiving antiretroviral therapy. Med Clin (Barc) 2001;117:607-10.
26. Reisler R, Servoss JC, Sherman KE. Incidence of hepatotoxicity and mortality in 21 adult antiretroviral treatment trials: ACTG LiverDiseases Focus Group [abstract 43]. In: Program and abstracts of the 1st International AIDS Society Conference on HIV Pathogenesis and Treatment (Buenos Aires); 2001.
27. Stern J, Robinson P, Love J, Lanes S, Imperiale M, Mayers D. A comprehensive hepatic safety analysis of nevirapine in different populations of HIV infected patients. J Acquir Immune Defic Syndr 2003;34:S21-33.
28. Wit FW, Weverling GJ, Weel J, Jurriaans S, Lange JM. Incidence of and risk factors for severe hepatotoxicity associated antiretroviralcombination therapy. J Infect Dis 2002;186:23-31.
29. Bhanukumar M, Vineetha BM, Justin K. Nevirapine induced stevens johnson syndrome: A case report. Int J Pharm Pharm Sci 2015;7:520-1.
30. Coffie PA, Tonwe GB, Tanon AK. Incidence and risk factors of severe adverse events with nevirapine based antiretroviral therapy in HIV-infected women. MTCT Plus program, Abidjan, Cˆote d’Ivoire. BMC Infect Dis 2010;10:188.
31. Van Griensven J, Zachariah R, Rasschaert F, Mugabo J, Att´e EF, Reid T. Stavudine-and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: Incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda. Trans R Soc Trop Med Hyg 2010;104:148-53.
32. Van Griensven J, De Naeyer L, Uwera J, Asiimwe A, Gazille C, Reid T. Success with antiretroviral treatment for children in Kigali, Rwanda: Experience with health center/nurse-based care. BMC Pediatr 2008;8:39.
33. Lohoues Essis EC, Johnson ND, Dion LM, Dechi JJ, N’Din JL, Camara CM. Polymorphism of reverse transcriptase and protease associated with antiretroviral(ARV) inefficiency in people living with human immune deficiency virus type 2 (HIV-2) in Abidjan, Cote d’ivoire. Int J Pharm Pharm Sci 2015;7:210-2.
34. Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Replyto MR. NNRTI-related or unrelated hepatotoxicity [letter]. Hepatology 2002;36:513-4.
35. José Antonio MM, Jesús GM, BernardoHoracio GC, José Luis FA, Carla Ileana AA, Alfaro MA. Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients: A concordance cross-sectional study. Virol J 2009;6:181.
36. Adiga U, Malawadi BN. Alterations of serum transaminases in HIV patients on ART. Natl J Lab Med 2017;6:BO05-8.
37. Judi L, Toukan A, Khader Y, Ajlouni K, Khatib MA. Prevalence of elevated hepatic transaminases among Jordanian patients with type 2 diabetes mellitus. Ann Saudi Med 2010;30:25-32.
38. Spengler U, Lichterfeld M, Rockstroh JK. Antiretroviral drug toxicity- a challenge to the hepatologist? J Hepatol 2002;36:283-94.
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How to Cite
Mn, A. S., and A. U. S. “EFFECT OF ANTIRETROVIRAL TREATMENT REGIMENS ON LIVER ENZYMES IN HUMAN IMMUNODEFICIENCY VIRUS PATIENTS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 8, Aug. 2018, pp. 95-99, doi:10.22159/ajpcr.2018.v11i8.24885.
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