Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir/ritonavir in HIV-infected, therapy-naïve patients: results of the EPIC study (CCR100136).

Background This phase IIb study explored the antiviral activity and safety of the investigational CC chemokine receptor 5 (CCR5) antagonist aplaviroc (APL) in antiretroviral-naive patients harbouring R5- or R5X4-tropic virus. Methods A total of 191 patients were randomized 2: 2: 2: 1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily ( bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100mg bid. Efficacy, safety and pharmacokinetic parameters were assessed. Results This study was terminated prematurely because of APL-associated idiosyncratic hepatotoxicity. A total of 141 patients initiated treatment early enough to have been able to complete 12 weeks on treatment [ modified intent-to-treat (M-ITT) population]; of these, 133 completed the 12-week treatment phase. The proportion of subjects in the M-ITT population with HIV-1 RNA < 400 copies/mL at week 12 was 50, 48, 54 and 75% in the APL 200mg bid, APL 400mg bid, APL 800mg once a day (qd) and 3TC/ZDV arms, respectively. Similar responses were seen in the few subjects harbouring R5X4-tropic virus (n=17). Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated nonlinear pharmacokinetics with high interpatient variability. Conclusions While target plasma concentrations of APL were achieved, the antiviral activity of APL+LPV/r did not appear to be comparable to that of 3TC/ZDV+LPV/r.