Table 4.
Clinical trial evaluation of hepatic toxicity and incidence for integrase strand transfer inhibitors.
| Reference | Drug(s) | No. of Study Patients | Hepatic Evaluation | Overall Incidence of Cases/100 Persons Exposed | Study Design | Patient Population |
|---|---|---|---|---|---|---|
| Steigbigel 2010 BENCHMRK-1 and -2 (Week 96 Pooled Data) [46] |
Raltegravir | 462 | AST/ALT > 10× ULN | AST: 0.7 ALT: 1.3 |
Prospective | Treatment-experienced; multidrug resistant |
| Lennox 2010 STARTMRK (Week 96 Data) [47] |
Raltegravir | 281 | AST/ALT/ALK Phos > 5× ULN TBILI > 2.5× ULN |
AST: 3.2 ALT: 1.8 ALK Phos: 0 TBILI: 0.7 |
Prospective | Treatment-naive; 6% HBV and/or HCV |
| DeJesus 2012 GS-236-0103 [48] |
Elvitegravir/cobicistat | 352 | Combination of all grades for AST/ALT elevations | AST: 17.6 ALT: 15.3 |
Prospective | Treatment-naive; 1% HBV; 5% HCV |
| Sax 2012 GS-US-236-0102 [49] |
Elvitegravir/cobicistat | 347 | Combination of all grades for AST/ALT elevations | AST: 15 ALT: 18 |
Prospective | Treatment-naive; 1% HBV; 5% HCV |
| Squillace 2017 SCOLTA [50] |
Elvitegravir/cobicistat | 280 | Grade 1–2: AST/ALT 1.25–2.4× ULN (if baseline WNL) or baseline (if baseline value abnormal) Grade 3–4: AST/ALT ≥2.5× ULN (if baseline WNL) or baseline (if baseline value abnormal) |
Grade 1–2; treatment-naive: 3.8 Grade 1–2; treatment-experienced: 8.5 Grade 3–4; treatment-naive: 1.3 Grade 3–4; treatment-experienced: 1 |
Prospective | 72.1% treatment-experienced; 27.9% treatment-naive; 21.8% HCV |
| Min 2011 [51] | Dolutegravir | 28 | Combination of all grades for AST/ALT elevations | 0 | Prospective | Treatment-experienced and treatment-naive; integrase strand transfer inhibitor-naive |
| van Lunzen 2012 SPRING-1 [52] |
Dolutegravir | 205 | AST/ALT ≥ 5× ULN | 0.5 | Prospective | Treatment-naive; 9% HCV |
| Raffi 2013 SPRING-2 [53] |
Dolutegravir | 411 | AST/ALT ≥ 5× ULN | 0.5 | Prospective | Treatment-naive; 2% HBV; 10% HCV |
| Sax 2017 [54] | Bictegravir | 64 | Grade 2–4: AST/ALT ≥ 2.5× ULN | AST: 9 ALT: 6 |
Prospective | Treatment-naive |
| Gallant 2017 GS-US-380-1489 [55] |
Bictegravir | 314 | Grade 3–4: AST/ALT ≥ 5× ULN | AST: 5 ALT: 2 |
Prospective | Treatment-naive |
| Sax 2017 GS-US-380-1490 [56] |
Bictegravir | 314 | Grade 3–4: AST/ALT ≥ 5× ULN | AST: 2 ALT: 3 |
Prospective | Treatment-naive; 3% HBV; 2% HCV |
| Markowitz 2017 ECLAIR [57] |
Cabotegravir | 94 | Grade 2–4: AST/ALT | 1 | Prospective | HIV-uninfected |
| Rizzardini 2020 FLAIR and ATLAS (Week 48 Pooled Data) [58] |
Cabotegravir | 591 | AST/ALT ≥ 5× ULN | 2 | Prospective | Treatment-experienced; 7% HCV |
Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; HBV, hepatitis B virus; HCV, hepatitis C virus; ULN, upper limit of normal.