Abstract
Objective
To compare the profile of adverse drug reactions (ADRs) to antiretroviral (ARV) drugs in patients coinfected with hepatitis C virus (HCV) or hepatitis B virus (HBV) versus non-coinfected patients with human immunodeficiency virus (HIV) infection.
Methods
We used the French Pharmacovigilance Database from 2000 to 2002. Selected patients were classified into four groups: HIV+HCV, HIV+HBV, HIV+HBV+HCV and HIV patients. We compared patients’ characteristics and profiles of ADRs to ARV drugs between the four groups.
Results
We identified 1,068 HIV, 172 HIV+HCV, 72 HIV+HBV and 26 HIV+HBV+HCV patients with 2,398, 446, 183 and 70 ADRs related to ARV drugs, respectively. The “seriousness” of these ADRs was similar in HIV and coinfected patients but death related to the ADRs was more frequent in HIV+HCV (9.4%) than in HIV (3.6%) patients (p<0.001). “Liver and bile system disorders” were more frequently reported in HIV+HCV and HIV+HBV patients than in HIV patients (17.3% and 20.8%, respectively, versus 8.9%, p<0.001). In HIV+HBV patients, the occurrence of these ADRs was independently associated in a logistic regression model to male gender [odds ratio (OR): 9.28, 95% confidence interval (CI): 2.74–31.36], exposure to zalcitabine (OR: 17.82, 95% CI: 1.49–212.95) or efavirenz (OR: 5, 95% CI: 1.44–17.33). “Red blood cell disorders” were also more frequent in HIV+HCV (7.4%) than in HIV (4.4%) patients (p<0.01).
Conclusion
Hepatic or haematological (mainly anaemia) ADRs to ARV drugs are more frequent in coinfected patients than in HIV patients. This study underlines the importance of hepatitis B or C in the occurrence of ADRs in HIV patients on ARV drugs.
Similar content being viewed by others
References
Bruno R, Sacchi P, Puoti M, Soriano V, Filice G (2002) HCV chronic hepatitis in patients with HIV: clinical management issues. Am J Gastroenterol 97:1598–1606
Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 338:853–860
Lewden C, Salmon D, Morlat P, Bevilacqua S, Jougla E, Bonnet F, Heripret L, Costagliola D, May T, Chene G (2005) Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS. Int J Epidemiol 34:121–130
Malavaud B, Dinh B, Bonnet E, Izopet J, Payen JL, Marchou B (2000) Increased incidence of indinavir nephrolithiasis in patients with hepatitis B or C virus infection. Antiviral Ther 5:3–5
Sulkowski MS, Thomas DL, Chaisson RE, Moore RD (2000) Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 283:2526–2527
Rodriguez-Rosado R, Garcia-Samaniego J, Soriano V (1998) Hepatotoxicity after introduction of highly active antiretroviral therapy. AIDS 12:1256
Soriano V, Rodriguez-Rosado R, Garcia-Samaniego J (1999) Management of chronic hepatitis C in HIV-infected patients. AIDS 13:539–546
Food and Drug Administration, HHS (2004) International Conference on Harmonisation; guidance on Addendum to E2C Clinical Safety Data Management: periodic safety update reports for marketed drugs. Fed Regist 69:5551–5552
Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356:1255–1259
Begaud B, Evreux JC, Jouglard J, Lagier G (1985) Imputation of the unexpected or toxic effects of drugs. Actualization of the method used in France. Therapie 40:111–118
Thiessard F, Roux E, Miremont-Salame G, Fourrier-Reglat A, Haramburu F, Tubert-Bitter P, Begaud B (2005) Trends in spontaneous adverse drug reaction reports to the French pharmacovigilance system (1986–2001). Drug Saf 28:731–740
Lemeshow S, Hosmer DW (1982) A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol 115:92–106
Begaud B, Martin K, Haramburu F, Moore N (2002) Rates of spontaneous reporting of adverse drug reactions in France. JAMA 288:1588
Belton KJ (1997) Attitude survey of adverse drug-reaction reporting by health care professionals across the European Union. Eur J Clin Pharmacol 52:423–427
Pierfitte C, Begaud B, Lagnaoui R, Moore ND (1999) Is reporting rate a good predictor of risks associated with drugs? Br J Clin Pharmacol 47:329–331
Gouezel P, Salmon D, Pialoux G, Holstein J, Delarocque-Astagneau E (2002) Co-infection VIH-VHC à l’hôpital, enquête nationale Juin 2001. Institut de Veille Sanitaire, pp 1–71
Fellay J, Boubaker K, Ledergerber B, Bernasconi E, Furrer H, Battegay M, Hirschel B, Vernazza P, Francioli P, Greub G, Flepp M, Telenti A, Swiss HIV Cohort Study (2001) Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study. Lancet 358:1322–1327
Chiffoleau A, Veyrac G, Brunet-François C, Raffi F, Bourin M, Jolliet P (2002) Systematic survey of antiretroviral drugs’ adverse effects: first results of a co-operative study in the centre of pharmacovigilance and the centre for disease control and prevention of Nantes. Lett Pharmacol 16:13–19
Baudrant M, Bagheri H, Cuzin L, Sommet A, Bassoua V, Guitton E, Bonnet E, Garipuy D, Lucas F, Aquilina C, Montastruc JL, Massip P Analysis of antiretroviral drug-induced adverse effects. Thérapie (in press)
Bergersen BM, Sandvik L, Bruun JN, Tonstad S (2004) Elevated Framingham risk score in HIV-positive patients on highly active antiretroviral therapy: results from a Norwegian study of 721 subjects. Eur J Clin Microbiol Infect Dis 23:625–630
Mann R, Andrews E (2002) Pharmacovigilance. John Wiley and Sons, Chichester
Bica I, McGovern B, Dhar R, Stone D, McGowan K, Scheib R, Snydman DR (2001) Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 32:492–497
Monga HK, Rodriguez-Barradas MC, Breaux K, Khattak K, Troisi CL, Velez M, Yoffe B (2001) Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection. Clin Infect Dis 33:240–247
Greub G, Ledergerber B, Battegay M, Grob P, Perrin L, Furrer H, Burgisser P, Erb P, Boggian K, Piffaretti JC, Hirschel B, Janin P, Francioli P, Flepp M, Telenti A (2000) Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 356:1800–1805
Law WP, Dore GJ, Duncombe CJ, Mahanontharit A, Boyd MA, Ruxrungtham K, Lange JM, Phanuphak P, Cooper DA (2003) Risk of severe hepatotoxicity associated with antiretroviral therapy in the HIV-NAT Cohort, Thailand, 1996–2001. AIDS 17:2191–2199
Bonnet F, Lawson-Ayayi S, Thiebaut R, Ramanampamonjy R, Lacoste D, Bernard N, Malvy D, Bonarek M, Djossou F, Beylot J, Dabis F, Morlat P, French Aquitaine Cohort, Groupe d’Epidemiologie Clinique du SIDA en Aquitaine (GECSA) (2002) A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997–1999. Clin Infect Dis 35:1231–1237
Aceti A, Pasquazzi C, Zechini B, De Bac C, Group LIVERHAART (2002) Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection. JAIDS 29:41–48
Arribas JR, Ibanez C, Ruiz-Antoran B, Pena JM, Esteban-Calvo C, Frias J, Vazquez JJ, Gonzalez-Garcia JJ (1998) Acute hepatitis in HIV-infected patients during ritonavir treatment. AIDS 12:1722–1724
Wit FW, Weverling GJ, Weel J, Jurriaans S, Lange JM (2002) Incidence of and risk factors for severe hepatotoxicity associated with antiretroviral combination therapy. J Infect Dis 186:23–31
Opravil M, Ledergerber B, Furrer H, Hirschel B, Imhof A, Gallant S, Wagels T, Bernasconi E, Meienberg F, Rickenbach M, Weber R, Swiss HIV Cohort Study (2002) Clinical efficacy of early initiation of HAART in patients with asymptomatic HIV infection and CD4 cell count >350×10(6)/l. AIDS 16:1371–1381
Mocroft A, Devereux H, Kinloch-de-Loes S, Wilson D, Madge S, Youle M, Tyrer M, Loveday C, Phillips AN, Johnson MA (2000) Immunological, virological and clinical response to highly active antiretroviral therapy treatment regimens in a complete clinic population. Royal free centre for HIV medicine. AIDS 14:1545–1552
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
The French Network of Pharmacovigilance Centres., Guitton, E., Montastruc, JL. et al. Influence of HCV or HBV coinfection on adverse drug reactions to antiretroviral drugs in HIV patients. Eur J Clin Pharmacol 62, 243–249 (2006). https://doi.org/10.1007/s00228-005-0080-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-005-0080-0