Efficacy and safety of TMC278 in treatment-naïve, HIV-1-infected patients with HBV/HCV co-infection enrolled in the phase III ECHO and THRIVE trials

Introduction

TMC278 had a high virologic response rate, non-inferior to EFV, in two Phase III double-blind trials ECHO (TMC278-C209, NCT00540449) and THRIVE (TMC278-C215, NCT00543725) in treatment-naïve HIV-infected adult patients. As the use of NNRTIs, particularly nevirapine, has been associated with hepatic-related adverse events (AEs), especially in HIV/hepatitis B (HBV) and/or hepatitis C (HCV) co-infected patients, a subgroup analysis of these events was performed on the pooled Week 48 Phase III data.

Methods

Patients (N=1368) with alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) ≤ 5x upper limit of normal received TMC278 25mg qd or EFV 600mg qd, plus TDF/FTC (ECHO) or TDF/FTC, AZT/3TC or ABC/3TC (THRIVE). HIV/HBV and/or HCV co-infection status was determined at baseline in 1335 patients by HBV surface antigen, HCV antibody and RNA testing.

Results

At baseline, 112/1335 patients (8.4%) had evidence of HIV/HBV and/or HCV co-infection (randomised to TMC278, n=49: 7.3%; EFV, n=63: 9.5%). Table 1 summarises the outcomes.

Compared with HIV mono-infected patients, co-infected patients had more hepatic AEs (clinical and laboratory) and lower virologic responses, which were similar across treatment groups. Hepatic AEs rarely led to treatment discontinuation (TMC278: n=3 vs. EFV: n=9 patients). There were no fatal hepatic AEs.

Table 1

Conclusions

Overall, both TMC278 and EFV were well tolerated with no hepatic safety differences observed. Hepatic AEs were more common in co-infected than in HIV mono-infected patients (27% vs. 4%, respectively), but there were no differences between the two treatment groups. Virologic responses were similar for TMC278 and EFV within the co-infected and HIV mono-infected groups, and lower in co-infected than in HIV mono-infected patients.