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

摘要

Purpose of study Safety and efficacy of raltegravir (RAL) in patients (pts) with HIV and hepatitis B and/or C (HBV/HCV) co‐infection were evaluated in a double‐blind fashion for 5 years in STARTMRK and 3 years in BENCHMRK‐1&2. Methods In STARTMRK, treatment‐na?ve pts received RAL 400 mg bid or efavirenz (EFV) 600 mg qhs, both with tenofovir+emtricitabine (TDF/FTC), for up to 240 weeks. In BENCHMRK‐1&2, highly treatment‐experienced pts with multidrug‐resistant virus and failing other therapies received double‐blind RAL 400 mg bid or placebo, both with optimized background therapy (OBT), for up to 156 weeks. Pts with stable chronic HBV/HCV could enroll if baseline AST and ALT were=5×upper limit of normal. Summary of results 743 pts received RAL and 519 received comparator. Hepatitis co‐infection was present in 6% (34/563) of treatment‐na?ve pts (HBV=4%, HCV=2%, HBV+HCV=0.2%) and 16% (114/699) of treatment‐experienced pts (HBV=6%, HCV=9%, HBV+HCV=1%). Safety and efficacy results at the end of double‐blind treatment are shown by study, treatment group and co‐infection status. Liver enzyme elevations were more common in pts with HIV+HBV/HCV co‐infection than in pts with HIV infection alone, in the RAL and control groups. Most liver enzyme changes occurred in the first 48 weeks of treatment, with minimal further increases (data not shown). Conclusion RAL was efficacious and generally well tolerated for up to 5 years in pts with HIV+HBV/HCV co‐infection. The majority of grade 3 and grade 4 liver enzyme elevations occurred during the first year of treatment and were more common among co‐infected pts than among HIV mono‐infected pts, irrespective of treatment group. STARTMRK (treatment‐naive), 240 weeks BENCHMRK (treatment‐experienced), 156 weeks RAL+TDF/FTC EFV+TDF/FTC RAL+OBT Placebo+OBT HBV or HCV positive N=18 % HBV … HCV negative N=263% HBV or HCV positive N=16% HBV … HCV negative N=266% HBV or HCV positive N=77 (PYR=182) % (rate/100 PYR)? HBV … HCV negative N=385 (PYR=869) % (rate/100 PYR)? HBV or HCV positive N=37 (PYR=43) % (rate/100 PYR)? HBV … HCV negative N=200 (PYR=280) % (rate/100 PYR)? Aspartate aminotransferase (AST) increased Grade 3? 5.6 4.6 0 3.0 9.1 (3.8) 3.4 (1.5) 2.7 (2.3) 3.0 (2.1) Grade 4? 5.6 0.8 6.3 0 2.6 (1.1) 0.3 (0.1) 0 1.5 (1.1) Alanine aminotransferase (ALT) increased Grade 3? 0 1.9 6.3 1.9 10.4 (4.4) 3.6 (1.6) 8.1 (7.0) 1.5 (1.1) Grade 4? 5.6 1.5 6.3 0.4 3.9 (1.6) 0.8 (0.3) 0 2.0 (1.4) Bilirubin increased Grade 3? 0 0.8 0 0 3.9 (1.6) 2.9 (1.3) 5.4 (4.7) 2.0 (1.4) Grade 4? 0 0.4 0 0 1.3 (0.5) 0.8 (0.3) 0 0 Clinical adverse events, % Any clinical AE 94.4 96.6 93.8 98.1 93.6 94.0 86.5 90.5 Discontinued 5.6 4.9 6.3 8.3 3.8 4.7 2.7 6.0 Hepatobiliary AE 5.6 5.7 0 3.4 7.8 4.2 5.4 5.5 Discontinued 5.6 0.4 0 0.4 0 0.5 0 0.4 Efficacy: % with HIV RNA