Share This Article:

Monitoring of Early Field Hepatic Tolerance to NNRTI-Based Regimens with Multiple Biochemical Parameters in Ivorian HIV-1-Infected Patients: A Pilot Study

Abstract Full-Text HTML Download Download as PDF (Size:474KB) PP. 79-89
DOI: 10.4236/pp.2012.31012    4,404 Downloads   7,418 Views   Citations

ABSTRACT

Background: Multiple biochemical parameters related to cytolysis, cholestasis and/or liver failure, can be used to evaluate liver tolerance to antiretroviral (ARV) drugs. what parameters are most suitable for monitoring early hepatic tolerance in the developing countries? Objective: to evaluate liver tolerance to NVP (nevirapine) or EFV (efavirenz)- based regimens during the first six months. Method: This is a preliminary prospective cohort study with 125 naive ivorian HIV1-infected patients, by observing the level of ALT (alanine aminotransferase), AST (aspartate aminotrans- ferase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transferase), and TBR (total bilirubin). Results: variable changes are noticed in the level of various biochemical parameters from M0 to M6. Nevertheless, we found that the values of these parameters studied fall within normal ranges except for GGT which showed an increased level with NVP-based regimen. Biological liver tolerance to NVP or EFV-based regimen was good at M3 and M6 during therapy. The percentage of patients who had elevated ALT activity had tripled with each ARV regimen from M3 to M6. We noticed a decrease in the median value of transaminases (ALT and AST) from M0 to M6. This decrease was statistically significant for patients on EFV-based regimen from M0 to M3 and from M0 to M6. The ALP enzymes were the least affected after initiation of therapy, regardless of the regimen taken. In general,we noticed an hepatotoxicity of grade 1 or 2, in the two ARV regimens. The hepatotoxicity of grade 3 or 4 were rare (only with transaminases and GGT). Conclusion: we suggest a study of longer duration involving more patients, probably limited to the monitoring of transaminases (ALT and AST) and GGT, due to the results more or less sensitive about them in our analysis.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

B. Kamenan, D. Abrogoua, A. Djadji and D. Monnet, "Monitoring of Early Field Hepatic Tolerance to NNRTI-Based Regimens with Multiple Biochemical Parameters in Ivorian HIV-1-Infected Patients: A Pilot Study," Pharmacology & Pharmacy, Vol. 3 No. 1, 2012, pp. 79-89. doi: 10.4236/pp.2012.31012.

References

[1] ONUSIDA, “Rapport mondial sur l’épidémie du sida,” 2009.
[2] OMS, Organisation Mondiale de la Santé, “Traitement antirétroviral de l’infection à VIH chez l’adulte et l’adolescent en situation de ressources limitées: vers un accès universel,” Recommandations pour une approche de santé publique, Version 2006, Genève WC 503.2, 2008.
[3] S. P. Eholié, K. A. Tanon, M. Folquet-Amorissani, I. Ouattara, Y. T. Aba, V. Traoré-Ettiegne, et al., “Bilan de l’accès aux antirétroviraux en C?te d’Ivoire,” Médecine Tropicale, Vol. 69, No. 5, 2009, pp. 520-524.
[4] V. J. Merluzzi, K. D. Hargrave, M. Labadia, et al., “Inhibition of HIV-1 Replication by a Non-Nucleoside Reverse Transcriptase Inhibitor,” Science, Vol. 250, No. 4986, 1990, pp. 1411-1413. doi:10.1126/science.1701568
[5] F. V. L. Eth, P. Hanuphak, R. K. Uxrungtham, et al., “Comparison of First-Line Antiretroviral Therapy with Regimens Including Nevirapine, Efavirenz, or Both Drugs, plus Stavudine and Lamivudine: A Randomised Open-Label Trial, the 2NN Study,” Lancet, Vol. 363, No. 9417, 2004, pp. 1253-1263. doi:10.1016/S0140-6736(04)15997-7
[6] R. M. Selik, R. H. Byers Jr. and M. S. Dworkin, “Trends in Diseases Reported on US Death Certificates That Mentioned HIV Infection, 1987-1999,” Journal of Acquired Immune Deficiency Syndromes, Vol. 29, No.4, 2002, pp. 378-387.
[7] A. Shakil, D. Kramer, G. Mazariegos, J. J. Fung and J. Rakela, “Acute Liver Failure: Clinical Features, Outcome Analysis, and Applicability of Prognostic Criteria,” Liver Transplantation, Vol. 6, No.2, 2000, pp. 163-169.
[8] H. Zimmerman, “Drug-Induced Liver Disease,” In: E. Schiff, W. Sorrell and W. Muldrey, Eds., Schiff’s Diseases of the Liver, 8th Edition, Lippincott-Raven Publishers, Philadelphia, 1999, pp. 973-1064.
[9] J. Servoss, D. Kitch, J. Andersen, et al., “Predictors of Antiretroviral-Related Hepatotoxicity in the Adult AIDS Clinical Trial Group (1989-1999),” Journal of Acquired Immune Deficiency Syndromes, Vol. 43, No. 3, 2006, pp. 320-323. doi:10.1097/01.qai.0000243054.58074.59
[10] V. Soriano, M. Puoti, P. Garcia-Gasco, J. K. Rockstroh, Y. Benhamou, P. Barreiro and B. McGovern, “Antiretroviral Drugs and Liver Injury,” AIDS, Vol. 22, No. 1, 2008, pp. 1-13. doi:10.1097/QAD.0b013e3282f0e2fd
[11] F. W. N. M. Wit, G. J. Weverling, J. Weel, S. Jurriaans and J. M. A. Lange, “Incidence and Risk Factors For severe Hepatotoxicity Associated with Antiretroviral Therapy,” Journal of Infectious Diseases, Vol. 186, No.1, 2002, pp. 23-31. doi:10.1086/341084
[12] P. Yeni, “Prise en charge des personnes infectées par le VIH: recommandations du groupe d’experts,” Médecine-Sciences, Paris, Flammarion, 2008, 412 Pages.
[13] E. Gisolf, C. Dreezen and S. Danner, “Risk Factors for Hepatoxicity in HIV-1 Infected Patients Receiving Ri- tonavir and Saquinavir with or without Stavudine,” Clinical Infectious Diseases, Vol. 31, No. 1, 2000, pp. 1234-1239. doi:10.1086/317449
[14] B. Kees, J. M. Hadewych and H. Ter, “Adverse Effects of Reverse Transcriptase Inhibitors: Mitochondrial Toxicity as Common Pathway,” Journal of Acquired Immune Deficiency Syndromes, Vol. 12, No. 14, 1998, pp. 1735- 1744.
[15] V. Montessori, N. Press, M. Harris, L. Akagi and S. Montaner, “Adverse Effects of Antiretroviral for HIV Infection,” Canadian Medical Association Journal, Vol. 170, No. 2, 2004, pp. 229-238.
[16] A. M. Cattelan, E. Erne, A. Saltino, et al., “Severe He- patic Failure Related to Nevirapine Treatment,” Clinical Infectious Diseases, Vol. 29, No. 2, 1999, pp. 455-456. doi:10.1086/520242
[17] P. Bossi, D. Colin, F. Bricaire and E. Caumes, “Hyper- sensitivity Syndrome Associated with Efavirenz Therapy,” Clinical Infectious Diseases, Vol. 30, No. 1, 2000, pp. 227-228. doi:10.1086/313629
[18] M. S. Sulkowski, D. L. Thomas, S. H. Mehta, R. E. Chaisson and R. D. Moore, “Hepatotoxicity Associated with Nevirapine or Efavirenz-Containing Antiretroviral Therapy: Role of Hepatitis C and B Infections,” Hepatology, Vol. 35, No.1, 2002, pp. 182-189. doi:10.1053/jhep.2002.30319
[19] D. Gonzalez de Requena, M. Nunez, I. Jimenez-Nacher and V. Soriano, “Liver Toxicity Caused by Nevirapine,” AIDS, Vol. 16, No.2, 2002, pp. 290-291. doi:10.1097/00002030-200201250-00020
[20] Boehringer-Ingelheim International Viramune product monograph, version 3.0, Ingelheim am Rhein, Boehringer-Ingelheim International GmbH, Germany.
[21] R. Verdon, M. Six, P. Rousselot and C. Bazin, “Efavirenz-Induced Acute Eosinophilic Hepatitis,” Jour- nal of Hepatology, Vol. 34, 2001, No. 5, pp. 783-785.
[22] R. Reisler, S. Liou, J. Servoss, G. Robbins, D. Theodore, R. Murphy and R. Chung, “Incidence of Hepatotoxicity and Mortality in 21 Adult Antiretroviral Treatment Trials [Abstract 43],” 1st International AIDS Society on HIV Pathogenesis and Treatment, 8-11 July 2001, Buenos Aires, Argentina.
[23] C. Danel, R. Moh, A. Anzian, Y. Abo, H. Chenal, C. Guehi, et al., “Tolerance and Acceptability of an Efavirenz-Based Regimen in 740 Adults (Predominantly Women) in West Africa,” Journal of Acquired Immune Deficiency Syndromes, Vol. 42, No. 1, 2006, pp. 29-35. doi:10.1097/01.qai.0000219777.04927.50
[24] F. V. L. Eth, S. Andrews, B. Grinsztejn, et al., “The Effect of Baseline CD4 Cell Count and HIV-1 Viral Load on The Efficacy and Safety of Nevirapine or Efavirenz- Based First-Line HAART,” AIDS, Vol. 19, No. 5, 2005, pp. 463-447. doi:10.1097/01.aids.0000162334.12815.5b
[25] S. Zucker, X. Qin, S. Rouster, F. Yu, R. Green, P. Ke- shavan, et al., “Mechanism of Indinavir-Induced Hyper- bilirubinemia,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, 2001, No. 22, pp. 12671-12676.
[26] S. Rodriguez-Novoa, P. Barreiro, A. Rendon, A. Barrios, A. Corral, I. Jimenez-Nacher, et al., “Plasma Levels of Atazanavir and the Risk of Hyperbilirubinemia Are Predicted by the 3435C-T Polymorphism at the Multidrug Resistance Gene 1,” Clinical Infectious Diseases, Vol. 42, No. 2, 2006, pp. 291-295. doi:10.1086/499056
[27] T. Lankisch, U. Moebius, M. Wehmeier, G. Behrens, M. Manns, R. Schmidt, et al., “Gilbert’s Disease and Ata- zanavir: From Phenotype to UDP-Glucuronosyltrans-ferase Haplotype,” Hepatology, Vol. 44, No. 5, 2006, pp. 1324-1332. doi:10.1002/hep.21361
[28] P. Miailhes, M. Trabaud, P. Pradat, et al., “Impact of Highly Active Antiretroviral Therapy (HAART) on the Natural History of Hepatitis B Virus (HBV) and HIV Co-Infection: Relationship between Prolonged Efficacy of HAART and HBV Surface and Early Antigen Seroconversion,” Clinical Infectious Diseases, Vol. 45, No. 5, 2007, pp. 624-632. doi:10.1086/520752
[29] O. Chauvel, K. Lacombe, P. Bonnard, et al., “Risk Factors for Acute Liver Enzyme Abnormalities in HIV Hepatitis B Virus-Coinfected Patients on Antiretroviral Therapy,” Antiviral Therapy, Vol. 12, No. 7, 2007, pp. 1115- 1126.
[30] M. De Maat, R. Mathot, A. Veldkamp, A. Huitma, J. Mulder, P. Meenhorst, et al., “Hepatotoxicity Following Nevirapine Containing Regimens in HIV-1-Infected Individuals,” Pharmacological Research, Vol. 46, No. 3, 2002, pp. 295-300. doi:10.1016/S1043-6618(02)00146-9
[31] A. Martin, D. Nolan, I. James, P. Cameron, J. Keller, C. Moore, et al., “Predisposition to Nevirapine Hypersensi- tivity Associated with HLA-DRB1M0101 and Abrogated by Low CD4 T-Cell Counts,” AIDS, Vol. 19, No. 13, 2005, pp. 97-99. doi:10.1097/00002030-200501030-00014
[32] S. Johnson, J. Chan and C. Bennett, “Hepatotoxicity after Prophylaxis with a Nevirapine-Containing Antiretroviral Regimen,” Annals of Internal Medicine, Vol. 137, No. 2, 2002, pp. 146-147.
[33] CDC, “1993 Revised Classification System for HIV Infection and expanded Surveillance Case Definition for AIDS among Adolescents and Adults—M.M.W.R.,” 41, No-RR17, 1992.
[34] S. P. Eholié and P. M. Girard, “Mémento thérapeutique du VIH/sida en Afrique,” Doin, Paris, 2005.
[35] A. Yapo, M. Assayi, N. Aka, R. Bonetto, L. Comoe, A. Lonsdorfer, D. Monnet and C. Diane, “Les valeurs de références de 21 constituants biochimiques sanguins de l’Ivoirien adulte présumé sain,” Publications méDicales Africaines, Vol. 110, 1990, pp. 49-57.
[36] OMS, “Grades de sévérité de certaines toxicités cliniques et biologiques,” Adapté à partir de documents de la Division of AIDS, National Institute of Allergy and Infectious Diseases, USA. In Traitement antirétroviral de l’infection à VIH chez l’adulte et l’adolescent en situation de ressources limitées: vers un accès universel, Recommandations pour une approche de santé publique, Version 2006, Genève WC 503.2, 2008, pp. 102-106.
[37] E. Martinez, J. L. Blanco, J. A. Arnaiz, J. B. Perez- Cuevas, A. Mocroft, A. Cruceta, M. A. Marcos, et al., “Hepatotoxicity in HIV-1-Infected Patients Receiving Nevirapine-Containing Antiretroviral Therapy,” AIDS, Vol. 15, No. 10, 2001, pp. 1261-1268. doi:10.1097/00002030-200107060-00007
[38] G. M. Lucas, R. E. Chaisson and R. D. Moore, “Comparison of initial Combination Antiretroviral Therapy with a Single Protease Inhibitor, Ritonavir and Saquinavir, or Efavirenz,” AIDS, Vol. 15, No. 13, 2001, pp. 1679- 1686. doi:10.1097/00002030-200109070-00011
[39] G. Moyle, “The Emerging Roles of Non-Nucleoside Reverse Transcriptase Inhibitors in Antiretroviral Therapy,” Drugs, Vol. 61, No. 1, 2001, pp. 19-26. doi:10.2165/00003495-200161010-00003
[40] G. Peytavin, R. Landman, C. Lamotte, A. Trylesinski, S. Legac, F. Mentre and P. Yeni, “Therapeutic Drug Monitoring of Nelfinavir in a Prospective Study in HIV-HCV Coin-fected Patients with Chronic Liver Disease [Abstract 349],” 1st International AIDS Society on HIV Pathogene-sis and Treatment, 8-11 July 2001, Buenos Aires, Argentina.
[41] R. Palmon, B. C. Koo, D. A. Shoultz and D. T. Dieterich, “Lack of Hepatotoxicity Associated with Non-nucleoside Reverse Transcriptase Inhibitors,” Journal of Acquired Immune Deficiency Syndromes, Vol. 29, No. 4, 2002, pp. 340-345.
[42] I. Sanne, H. Mommeja-Marin, J. Hinkle, J. A. Bartlett, M. M. Lederman, G. Maartens, C. Wakeford, A. Shaw, J. Quinn, R. G. Gish, and F. Rousseau, “Severe Hepatotox- icity Associated with Nevirapine Use in HIV-Infected Subjects,” Journal of Infectious Diseases, Vol. 191, No. 6, 2005, pp. 825-829. doi:10.1086/428093
[43] W. M. Lee, “Drug-Induced Hepatotoxicity,” New Eng- land Journal of Medicine, Vol. 349, No. 5, 2003, pp. 474-485. doi:10.1056/NEJMra021844
[44] M. Sulkowski, D. Thomas, R. Chaisson and R. Moore, “Hepatotoxicity Associated with Antiretroviral Therapy in Adult with Hu-man Immunodeficiency Virus and the Role of Hepatitis C or B Virus Infection,” Journal of the American Medical Association, Vol. 283, No. 1, 2000, pp. 74-80. doi:10.1001/jama.283.1.74
[45] G. Djoman, T. Roel, T. Ellerbrock, D. Hanson, F. Diomande and A. Kadio, “Virologic and Immunologic Outcomes and Programmatic Challenge of an Antiretroviral Treatment Pilot Project in Abidjan C?te d’Ivoire,” Journal of Ac-quired Immune Deficiency Syn- dromes, Vol. 17, No. 3, 2003, pp. 5-15.
[46] M. S. Sulkowski, D. L. Thomas, S. H. Mehta, R. E. Chaisson and R. D. Moore, “Reply to ‘NNRTI-Related or Unrelated Hepatotoxicity’ [Letter],” Hepatology, Vol. 36, No. 2, 2002, pp. 513-514. doi:10.1053/jhep.2002.34940
[47] N. Friis-Moller, O. Kirk, P. Reiss, et al., “Safety of Non-Nucleoside Reverse Transcriptase Therapy: Data from the EUROSIDA Study [Abstract 24],” In: Abstracts of the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV (Paris). Antiviral Therapy, Vol. 8, 2003, p. L20.
[48] A. L. Pozniak, R. Miller and L. P. Ormerod, “The Treatment of Tuberculosis in HIV-Infected Persons,” AIDS, Vol. 13, No. 4, 1999, pp. 435-45. doi:10.1097/00002030-199903110-00001
[49] P. Piliero and B. Purdy, “Nevirapine-Induced Hepatitis: A Case Series and Review of the Literature,” AIDS Reader, Vol. 11, No. 7, 2001, pp. 379-382.
[50] D. Dieterich, S. Becker, J. Fusco, et al., “Low Incidence of Grade III/IV Hepatotox-icity in First HAART Observations from 1237 Patients Followed for One Year (Poster 4534),” Program and Abstracts of the XIV Conference of the International AIDS Society (Barcelona), 2002.
[51] S. Becker, “Liver Toxicity in Epidemiological Cohorts,” Clinical Infectious Diseases, Vol. 38, Suppl. 2, 2004, pp. S49-55. doi:10.1086/381447
[52] S. Imperiale, S. Lanes, J. Stern, J. Love, P. Robinson and D. Mayers, “TARGET: Incidence of Elevated ALT/AST with HAART in a Large Observational Cohort [Abstract P150],” Program and Abstracts of the 6th International Congress on Drug Therapy in HIV Infection (Glasgow). 2002, p. 150.
[53] S. Clarke, P. Harrington, M. Barry, F. Mulcahy, “The Tolerability of Efavirenz after Nevirapine-Related Adverse Events,” Clinical Infectious Diseases, Vol. 31, No. 3, 2000, pp. 806-807. doi:10.1086/314026
[54] V. Soriano, C. Dona, P. Barreiro and J. Gonzalez-Lahoz, “Is There Cross-Toxicity between Nevirapine and Efavirenz in Subjects Developing Rash?” AIDS, Vol. 14, No. 11, 2000, pp. 1672-1673. doi:10.1097/00002030-200007280-00032
[55] W. Manosuthi, S. Thongyen, N. Chumpathat, K. Muang-chana and S. Sungkanuparph, “Incidence and Risk Factors of Rash Associated with Efavirenz in HIV-Infected Patients with Preceding Nevirapine-Associated Rash,” HIV Medicine, Vol. 7, No. 6, 2006, pp. 378-382. doi:10.1111/j.1468-1293.2006.00396.x

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.