Hepatoxicity of new antiretrovirals: A systematic review

Clinics and Research in Hepatology and Gastroenterology

Volumn 37, Issue 2, 2013, Pages 126-133

  Surgers, Laure ^a,b   Lacombe, Karine ^a,b,c  

^a SORBONNE UNIVERSITÉ   (France)

^b HÔPITAL SAINT ANTOINE   (France)

^c INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; ANTIRETROVIRUS AGENT; ATAZANAVIR; COBICISTAT; DARUNAVIR; DOLUTEGRAVIR; EFAVIRENZ; ELVITEGRAVIR; EMTRICITABINE; ETRAVIRINE; FOSAMPRENAVIR; INDINAVIR; LOPINAVIR; MARAVIROC; NEVIRAPINE; RALTEGRAVIR; RILPIVIRINE; RITONAVIR; SAQUINAVIR; TENOFOVIR;

DRUG EFFICACY; DRUG SAFETY; DRUG TOLERANCE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIVER TOXICITY; LONG TERM EXPOSURE; MIXED INFECTION; MONOTHERAPY; QUALITATIVE ANALYSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETROSPECTIVE STUDY; SHORT SURVEY; SYSTEMATIC REVIEW;

ANTI-RETROVIRAL AGENTS; CLINICAL TRIALS AS TOPIC; CYCLOHEXANES; DRUG-INDUCED LIVER INJURY; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; NITRILES; PYRIDAZINES; PYRIMIDINES; PYRROLIDINONES; QUINOLONES; SULFONAMIDES; TRIAZOLES;

EID: 84876730077     PISSN: 22107401     EISSN: 2210741X     Source Type: Journal    
DOI: 10.1016/j.clinre.2013.02.008     Document Type: Short Survey

References (69)

1. Fontana R., Seeff L., Andrade R., Bjoernsson E., Day C., Serrano J., et al. Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology 2010, 52:730-742.
2. Nunez M. Clinical syndromes and consequences of antiretroviral-related hepatotoxicity. Hepatology 2010, 52:1143-1155.
3. den Brinker M., Wit F.W., Wertheim-van Dillen P.M., Jurriaans S., Weel J., van Leeuwen R., et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 2000, 14:2895-2902.
4. Aithal G.P., Watkins P.B., Andrade R.J., Larrey D., Molokhia M., Takikawa H., et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011, 89:806-815.
5. ACTG, http://rsc.tech-res.com/Document/safetyandpharmacovigilance/Table_for_Grading_Severity_of_Adult_Pediatric_Adverse_Events.pdf.
6. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events, Version 4.0, Published: May 28, 2009 (v4.03: June 14, 2010) http://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5×7.pdf.
7. Madruga J.V., Berger D., McMurchie M., Suter F., Banhegyi D., Ruxrungtham K., et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet 2007, 370:49-58.
8. Lazzarin A., Campbell T., Clotet B., Johnson M., Katlama C., Moll A., et al. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007, 370:39-48.
9. Katlama C., Haubrich R., Lalezari J., Lazzarin A., Madruga J.V., Molina J.M., et al. Efficacy and safety of etravirine in treatment-experienced HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS 2009, 23:2289-2300.
10. Clotet B., Clumeck N., Katlama C., Nijs S., Witek J. Safety of etravirine in HIV-1/hepatitis B and/or C virus co-infected patients: pooled 96 week results from the Phase III DUET trials. J Antimicrob Chemother 2010, 65:2450-2454.
11. Girard P.M., Campbell T., Grinsztejn B., Hartikainen J., Rachline A., Nijs S., et al. Pooled week 96 results of the phase III DUET-1 and DUET-2 trials of etravirine: further analysis of adverse events and laboratory abnormalities of special interest. HIV Med 2012.
12. Gatti F. Hepatic toxicity of etravirine in HIV mono-infected and HIV-HCV co-infected patients enrolled in the Expanded Access Programme in the outpatients HIV-clinic of the Institute of Infectious and Tropical Diseases of Brescia. 2nd Italian Conference on AIDS and Retroviruses (ICAR) 2010.
13. Casado J. Low Risk of hepatotoxicity in HIV-infected patients receiving etravirine. 13th European Clinical AIDS Society Conference 2011.
14. Molina J.M., Cahn P., Grinsztejn B., Lazzarin A., Mills A., Saag M., et al. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet 2011, 378:238-246.
15. Cohen C.J., Andrade-Villanueva J., Clotet B., Fourie J., Johnson M.A., Ruxrungtham K., et al. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet 2011, 378:229-237.
16. Cohen C., Molina J., Cahn P., Clotet B., Fourie J., Grinsztejn B., et al. Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naïve, HIV-1-infected patients: Pooled results from the phase 3 double-blind, randomized ECHO and THRIVE trials. J Acquir Immune Defic Syndr 2012.
17. Pozniak A.L., Morales-Ramirez J., Katabira E., Steyn D., Lupo S.H., Santoscoy M., et al. Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial. AIDS 2010, 24:55-65.
18. Nelson M., Amaya G., Clumeck N., Arns da Cunha C., Jayaweera D., Junod P., et al. Efficacy and safety of rilpivirine in treatment-naive HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the Phase III randomized, double-blind ECHO and THRIVE trials. J Antimicrob Chemother 2012, 67:2020-2028.
19. Ahmed Y., Siddiqui W., Enoch C., Albrecht H., Bookstaver H. Rare case of rilpivirine-induced severe allergic hepatitis. J Antimicrob Chemother 2012, [Advanced access]. 10.1093/jac/dks400.
20. Moreno C., Gustot T., Nicaise C., Quertinmont E., Nagy N., Parmentier M., et al. CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice. Hepatology 2005, 42:854-862.
21. Mauss S., Puoti M. CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice--clinical implications for CCR5 inhibition as antiretroviral therapy. Hepatology 2006, 43:879. [author reply, 879-880].
22. Fätkenheuer G., Pozniak A.L., Johnson M.A., Plettenberg A., Staszewski S., Hoepelman A.I., et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med 2005, 11:1170-1172.
23. Cooper D.A., Heera J., Goodrich J., Tawadrous M., Saag M., Dejesus E., et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis 2010, 201:803-813.
24. Sierra-Madero J., Di Perri G., Wood R., Saag M., Frank I., Craig C., et al. Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study. HIV Clin Trials 2010, 11:125-132.
25. Gulick R.M., Lalezari J., Goodrich J., Clumeck N., DeJesus E., Horban A., et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 2008, 359:1429-1441.
26. Abel S., Back D.J., Vourvahis M. Maraviroc: pharmacokinetics and drug interactions. Antivir Ther 2009, 14:607-618.
27. Peytavin G. Clinical pharmacokinetic of maraviroc. Med Mal Infect 2008, 38(Suppl. 1):S12-S16.
28. Fätkenheuer G., Nelson M., Lazzarin A., Konourina I., Hoepelman A.I., Lampiris H., et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med 2008, 359:1442-1455.
29. Hardy W.D., Gulick R.M., Mayer H., Fätkenheuer G., Nelson M., Heera J., et al. Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96-week combined analysis of MOTIVATE 1 and 2. J Acquir Immune Defic Syndr 2010, 55:558-564.
30. Abel S., Davis J.D., Ridgway C.E., Hamlin J.C., Vourvahis M. Pharmacokinetics, safety and tolerability of a single oral dose of maraviroc in HIV-negative subjects with mild and moderate hepatic impairment. Antivir Ther 2009, 14:831-837.
31. Mangiafico L., Perja M., Fusco F., Riva S., Mago D., Gringeri A. Safety and effectiveness of raltegravir in patients with haemophilia and anti-HIV multidrug resistance. Haemophilia 2012, 18:108-111.
32. Maraviroc United States Prescribing Information. Pfizer inc. 2011.
33. Lennox J.L., DeJesus E., Lazzarin A., Pollard R.B., Madruga J.V., Berger D.S., et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet 2009, 374:796-806.
34. Lennox J.L., Dejesus E., Berger D.S., Lazzarin A., Pollard R.B., Ramalho Madruga J.V., et al. Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr 2010, 55:39-48.
35. Rockstroh J., Teppler H., Zhao J., Sklar P., Harvey C., Strohmaier K., et al. Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection. HIV Med 2011, 13:127-131.
36. Cooper D.A., Steigbigel R.T., Gatell J.M., Rockstroh J.K., Katlama C., Yeni P., et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008, 359:355-365.
37. Steigbigel R.T., Cooper D.A., Teppler H., Eron J.J., Gatell J.M., Kumar P.N., et al. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis 2010, 50:605-612.
38. Teppler H., Brown D.D., Leavitt R.Y., Sklar P., Wan H., Xu X., et al. Long-term safety from the raltegravir clinical development program. Curr HIV Res 2011, 9:40-53.
39. Rockstroh J.K., Lennox J.L., Dejesus E., Saag M.S., Lazzarin A., Wan H., et al. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis 2011, 53:807-816.
40. Rockstroh J., Sklar P., Wan H., Teppler H., Harvey C., Strohmaier K., et al. Safety and efficacy of raltegravir in patients co-infected with HIV and hepatitis B and/or C virus: complete data from Phase III double-blind studies. J Int AIDS Soc 2012, 15:18415.
41. Kassahun K., McIntosh I., Cui D., Hreniuk D., Merschman S., Lasseter K., et al. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos 2007, 35:1657-1663.
42. Vispo E., Mena A., Maida I., Blanco F., Cordoba M., Labarga P., et al. Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C. J Antimicrob Chemother 2010, 65:543-547.
43. Weimer L.E., Fragola V., Floridia M., Guaraldi G., Ladisa N., Francisci D., et al. Response to raltegravir-based salvage therapy in HIV-infected patients with hepatitis C virus or hepatitis B virus coinfection. J Antimicrob Chemother 2013, 68:193-199.
44. Hurt C., Napravnik S., Moore R.D., Eron J.E. Tolerability and hepatic safety of RAL among patients with HIV and viral hepatitis co-infection. 18th Conference on Retroviruses and Opportunistic Infections 2011.
45. Iwamoto M., Hanley W.D., Petry A.S., Friedman E.J., Kost J.T., Breidinger S.A., et al. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother 2009, 53:1747-1752.
46. Zhang K., Modi G., Hsu S. DRESS syndrome associated with raltegravir. Dermatol Online J 2011, 17:14.
47. Ortu F., Weimer L.E., Floridia M., Manconi P.E. Raltegravir, tenofovir, and emtricitabine in an HIV-infected patient with HCV chronic hepatitis, NNRTI intolerance and protease inhibitors-induced severe liver toxicity. Eur J Med Res 2010, 15:81-83.
48. DeJesus E., Berger D., Markowitz M., Cohen C., Hawkins T., Ruane P., et al. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J Acquir Immune Defic Syndr 2006, 43:1-5.
49. Elion R., Cohen C., Gathe J., Shalit P., Hawkins T., Liu H.C., et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. Aids 2011, 25:1881-1886.
50. Molina J.M., Lamarca A., Andrade-Villanueva J., Clotet B., Clumeck N., Liu Y.P., et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis 2012, 12:27-35.
51. DeJesus E., Rockstroh J.K., Henry K., Molina J.M., Gathe J., Ramanathan S., et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012, 379:2429-2438.
52. Sax P.E., DeJesus E., Mills A., Zolopa A., Cohen C., Wohl D., et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 2012, 379:2439-2448.
53. Min S., Sloan L., DeJesus E., Hawkins T., McCurdy L., Song I., et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS 2011, 25:1737-1745.
54. Raffi F., Rachlis A., Stellbrink H. Once-daily dolutegravir (DTG; S/GSK1349572) is non-inferior to raltegravir (RAL) in antiretroviral-naive adults: 48-week results from SPRING-2 (ING113086). XIX International AIDS Conference; July 22-27 2012, Abstract THLBB04.
55. van Lunzen J., Maggiolo F., Arribas J.R., Rakhmanova A., Yeni P., Young B., et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis 2012, 12:111-118.
56. Stellbrink H., Reynes J., Lazzarin A., Voronin E., Pulido F., Felizarta F., et al. Dolutegravir in Combination Therapy Exhibits Rapid and Sustained Antiviral Response in ARV-naïve Adults: 96-week Results from SPRING-1 (ING112276). 19th Conference on Retroviruses and Opportunistic Infections 2012, Abstract 102LB=.
57. Song I., Borland J., Savina P., Chen C., Patel P., Wajima T., et al. Pharmacokinetics of Dolutegravir in Subjects with Moderate Hepatic Impairment. 19th Conference on Retroviruses and Opportunistic Infections 2012, Abstract 608.
58. Ortiz R., Dejesus E., Khanlou H., Voronin E., van Lunzen J., Andrade-Villanueva J., et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS 2008, 22:1389-1397.
59. Mills A.M., Nelson M., Jayaweera D., Ruxrungtham K., Cassetti I., Girard P.M., et al. Once-daily darunavir/ritonavir vs lopinavir/ritonavir in treatment-naive HIV-1-infected patients: 96-week analysis. AIDS 2009, 23:1679-1688.
60. Clotet B., Bellos N., Molina J.M., Cooper D., Goffard J.C., Lazzarin A., et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet 2007, 369:1169-1178.
61. Arasteh K., Yeni P., Pozniak A., Grinsztejn B., Jayaweera D., Roberts A., et al. Efficacy and safety of darunavir/ritonavir in treatment-experienced HIV type-1 patients in the POWER 1, 2 and 3 trials at week 96. Antivir Ther 2009, 14:859-864.
62. Molina J.M., Cohen C., Katlama C., Grinsztejn B., Timerman A., Pedro ReJ, et al. Safety and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. J Acquir Immune Defic Syndr 2007, 46:24-31.
63. Rachlis A., Clotet B., Baxter J., Murphy R., Lefebvre E. Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3. HIV Clin Trials 2007, 8:213-220.
64. Morsica G., Bianchi G., Bagaglio S., Conte C., Salpietro S., Porrino L., et al. Hepatic safety profile of darunavir with low-dose ritonavir (DRV/r) in HIV/HCV coinfected and HIV monoinfected patients. New Microbiol 2011, 34:317-321.
65. Vispo E. Warning on hepatotoxicity of darunavir. AIDS Rev 2008, 10:63.
66. FDA alerts doctors to Prezista's possible link to liver damage, deaths. AIDS Read 2008,18:235.
67. May M., Gompels M., Delpech V., Porter K., Post F., Johnson M., et al. Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study. BMJ 2011, 343.
68. Konopnicki D., Mocroft A., de Wit S., Antunes F., Ledergerber B., Katlama C., et al. Hepatitis B and HIV: prevalence AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. Aids 2005, 19:593-601.
69. Rockstroh J.K., Mocroft A., Soriano V., Tural C., Losso M.H., Horban A., et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis 2005, 192:992-1002.