TABLE 2.
Subjects with treatment-emergent grade 3 or 4 elevations in ALT or total bilirubin levelsa
| Study and case no. | Regimenb | Age (yr), race, gender | BL CD4 count (no. of cells/mm3) | Onset | Peak abnormality | Commentc |
|---|---|---|---|---|---|---|
| ASCENT | ||||||
| 1 | APL 800 mg BID | 38, B, M | 283 | Wk 8 | ALT, 66× ULN; Bili, 7× ULN | Index case (see text) |
| 2 | APL 800 mg BID | 33, W, M | 228 | Wk 28 (FU) | ALT, 10× ULN | G2 ALT toxicity while on APL (wk 24); stopped APL when study closed; G3 toxicity while on ZDV-3TC-NVP |
| 3 | APL 600 mg BID | 47, W, M | 378 | Wk 8 | Bili, 3× ULN | G2 bili at screening; small fluctuations on therapy (max G3 toxicity) until study close |
| 4 | APL 600 mg BID | 36, W, M | 187 | Wk 24 (FU) | Bili, 3× ULN | No toxicity while on APL; WD at wk 20 with study closure; G3 Bili toxicity while on ABC-3TC-ATZ |
| 5 | APL 600 mg BID | 25, B, F | 283 | Wk 14 (FU) | Bili, 5× ULN | No toxicity while on APL; WD at wk 12 with study closure; G3 Bili toxicity while on ABC-3TC-ATZ-RTV |
| 6 | APL 600 mg BID | 43, W, M | 362 | Wk 20 (FU) | Bili, 5× ULN | G1 Bili toxicity while on APL; WD at wk 18 with study closure; G4 Bili toxicity while on ABC-3TC-ATZ |
| 7 | APL 800 mg BID | 25, W, M | 143 | Wk 26 (FU) | Bili, 12× ULN | Max G2 bili toxicity while on therapy from wk 2 until study close; G4 toxicity while on TDF-FTC-ATZ-RTV |
| 8 | APL 600 mg BID | 25, W, M | 87 | Wk 14 (FU) | Bili, 5× ULN | No toxicity while on APL; WD at wk 12 for nonresponse; G3 Bili while on TDF-3TC-ATZ-RTV |
| EPIC | ||||||
| 9 | APL 400 mg BID | 58, W, M | 339 | Wk 4 | ALT, 17× ULN; Bili, 3× ULN | ALT 3× ULN and fatty liver by U/S at BL (admitted EtOH use); increase in ALT levels, with fever, diarrhea, nausea |
| 10 | APL 400 mg BID | 37, W, M | 443 | Wk 16 | ALT, 9× ULN | Positive regimen dechallenge and rechallenge |
| 11 | APL 200 mg BID | 36, W, F | 314 | Wk 12 | ALT, 8× ULN | ALT 1.6× ULN and HCV positive at BL; admitted EtOH use |
| 12 | APL 400 mg BID | 38, W, M | 366 | Wk 20 (FU) | ALT, 16× ULN | HBsAg positive at BL; WD at wk 12 with study closure, G4 ALT toxicity while on TDF-FTC-FPV (admitted EtOH use) |
| 13 | APL 200 mg BID | 38, W, M | 265 | Wk 4 | Bili, 5× ULN | ALT 3× ULN and HBeAg positive at BL; admitted EtOH use |
| 14 | APL 400 mg BID | 32, W, M | 417 | Wk 12 | Bili, 3× ULN | Resolved with discontinuation of compazine and EtOH |
| 15 | APL 400 mg BID | 27, W, M | 246 | Wk 20 (FU) | Bili, 3× ULN | No toxicity while on APL; WD at wk 16 with study closure; G3 Bili toxicity while on ABC-3TC-EFV |
| 16 | APL 200 mg BID | 29, W, M | 297 | Wk 24 (FU) | Bili, 4× ULN | No toxicity while on APL; WD at wk 12 with study closure; G3 Bili toxicity while on ATZ-RTV |
| 17 | APL 400 mg BID | 42, W, M | 416 | Wk 36 (FU) | Bili, 4× ULN | No toxicity while on APL, WD at wk 24 with study closure; G3 Bili toxicity while on ATZ-RTV |
| 18 | APL 800 mg QD | 48, W, F | 345 | Wk 1 | Bili 3× ULN | WD after one dose of LPV-RTV (exclusionary ECG at BL); never received APL |
a
Abbreviations: BL, baseline; Bili, total bilirubin; B, black; W, white; M, male; F, female; FU, follow-up (after the subject had stopped taking APL); ABC, abacavir; ATZ, atazanavir; TDF, tenofovir; FTC, emtricitabine; HCV, hepatitis C virus; HBeAg, hepatitis B e antigen; WD, withdrawn; U/S, ultrasound; EtOH, alcohol; G2, grade 2; max, maximum; ECG, electrocardiography.
b
In the ASCENT study, all subjects received ZDV-3TC BID. In the EPIC study, all subjects received LPV-RTV BID.
c
Unless otherwise noted, all subjects were negative for hepatitis B and C viruses at the baseline.