Table 5.
Clinical trial evaluation of hepatic toxicity and incidence for protease inhibitors.
| Reference | Drug(s) | No. of Study Patients | Hepatic Evaluation | Overall Incidence of Cases/100 Persons Exposed | Study Design | Patient Population |
|---|---|---|---|---|---|---|
| Torti 2009 MASTER and Italian ATV [77] |
Atazanavir | 2404 | Grade 3–4: ALT > 5× ULN Grade 3–4 TBILI > 2.5× ULN |
ALT: 6.4 TBILI: 44.6 |
Retrospective | Longitudinal multicenter cohort; 47.3% HCV, 7.3% HBV |
| McDonald 2012 CASTLE [78] | Atazanavir/ ritonavir |
441 | Grade 3–4: AST/ALT > 5× ULN Grade 3–4 TBILI > 2.5× ULN |
AST: 3 ALT: 3 TBILI: 44 |
Prospective | Treatment-naive |
| Gallant 2017 [79] | Atazanavir/ ritonavir |
348 | Grade 3–4: AST/ALT > 5× ULN Grade 3–4 TBILI > 2.5× ULN GGT > 5× ULN |
AST: 3 ALT: 3 TBILI: 66 GGT: 2 |
Prospective | Treatment-naive |
| Atazanavir/ cobicistat |
344 | AST: 4 ALT: 4 TBILI: 73 GGT: 4 |
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| Walmsley 2002 Study 863 [80] (M-98-863) |
Lopinavir/ritonavir | 326 | Grade 3–4: AST/ALT > 5× ULN | AST or ALT: 4.5 | Prospective | Treatment-naive |
| González-García 2010 Study 730 [80] (M05-730) |
Lopinavir/ritonavir once daily | 333 | Grade 3–4: AST/ALT > 5× ULN | AST: 1 ALT: 1 |
Prospective | Treatment-naive |
| Lopinavir/ritonavir twice daily | 331 | AST: 2 ALT: 1 |
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| Pollard 2004 Study 888 [80] (M98-888) |
Lopinavir/ritonavir | 148 | Grade 3–4: AST/ALT > 5× ULN | AST: 5 ALT: 6 |
Prospective | Single PI-experienced, NNRTI-naive |
| Zajdenverg 2010 Study 802 [80] (M06-802) |
Lopinavir/ritonavir once daily | 300 | Grade 3–4: AST/ALT > 5× ULN | AST: 3 ALT: 2 |
Prospective | Treatment-experienced |
| Lopinavir/ritonavir twice daily | 299 | AST: 2 ALT: 2 |
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| Orkin 2013 ARTEMIS [81] Week 192 |
Lopinavir/ritonavir | 346 | Grade 2–4 AST/ALT Grade 2–4 TBILI |
AST: 14.9 ALT: 15.8 TBILI: 5.5 |
Prospective | Treatment-naive, HCV or HBV 12.5% (DRV/r) 13.9% (LPV/r) |
| Darunavir/ritonavir | 343 | AST: 12.9 ALT: 12.6 TBILI: 1.2 |
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| Madruga 2007 TITAN [82] |
Lopinavir/ritonavir | 297 | Grade 2–4 AST/ALT | AST: 9 ALT: 9 |
Prospective | Treatment-experienced, HCV or HBV 13% (LPV/r), 18%(DRV/r) |
| Darunavir/ritonavir | 298 | AST: 7 ALT: 9 |
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| Arasteh 2009 POWER-1, 2, 3 (Week 96 Pooled Data) [83] | Darunavir/ritonavir | 467 | Grade 2–4 AST/ALT Grade 2–4 TBILI |
AST: 10 ALT: 9 TBILI: 2 |
Prospective | Extensive treatment- experienced |
Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; DRV/r, darunavir/ritonavir; HBV, hepatitis B virus; HCV, hepatitis C virus; LPV/r, lopinavir/ritonavir; TBILI, total bilirubin; NNRTI, non-nucleoside reverse transcriptase inhibitor; ULN, upper limit of normal.