In STARTMRK, treatment-naïve patients received raltegravir

400 mg twice a day (bid) or efavirenz 600 mg at bedtime, both with tenofovir/emtricitabine. In BENCHMRK-1 and -2, highly treatment-experienced patients with multi-drug resistant virus and prior treatment failure received raltegravir 400 mg bid or placebo, both with optimized background therapy. Patients with chronic HBV and/or HCV coinfection were enrolled if baseline liver function tests were ≤5 times the upper limit of normal. HBV infection was defined PLX4032 as HBV surface antigen positivity for all studies; HCV infection was defined as HCV RNA positivity for STARTMRK and HCV antibody positivity for BENCHMRK. Hepatitis coinfection was present in 6% (34 of 563) of treatment-naïve patients (4% HBV only, 2% HCV only and 0.2% HBV+HCV) and 16% (114 of 699) of treatment-experienced patients (6% HBV only, 9% HCV only and 1% HBV+HCV). The incidence of drug-related adverse events was signaling pathway similar in raltegravir recipients with and without hepatitis coinfection in both STARTMRK (50 vs. 47%) and BENCHMRK (34 vs. 38.5%). Grade 2–4 liver enzyme elevations were more frequent in coinfected vs. monoinfected patients, but were not different between the raltegravir and control groups. At week 96, the proportion of raltegravir recipients with HIV RNA <50 HIV-1 RNA copies/mL was similar between coinfected and monoinfected patients (93 vs. 90% in STARTMRK;

63 vs. 61% in BENCHMRK). Raltegravir was generally well tolerated and efficacious up to 96 weeks in HIV-infected patients with HBV/HCV coinfection. World-wide prevalence rates for coinfection with HIV and Resveratrol hepatitis B virus (HBV) or hepatitis C virus (HCV) are estimated

at 5–15% and 25–33%, respectively [1–3], and liver diseases associated with HBV and HCV infections have emerged as a major cause of morbidity and mortality in persons with HIV infection [3–6]. Hepatitis coinfection is also associated with an increased risk for liver toxicity in HIV-infected patients receiving protease inhibitors or reverse transcriptase inhibitors [7–10]. Raltegravir is a novel HIV-1 integrase inhibitor that has demonstrated potent efficacy and a favourable safety profile in treatment-naïve and heavily treatment-experienced patients with HIV-1 infection [11–14]. The primary mechanism of raltegravir clearance is through hepatic metabolism mediated by UDP glucuronosyltransferase 1A1 [15]; moderate hepatic insufficiency does not have a clinically important effect on the pharmacokinetic profile of raltegravir [16]. We have examined the safety and efficacy of raltegravir in patients with HIV-1 and HBV and/or HCV coinfection who participated in three Phase III studies of raltegravir [11–14]. These post hoc analyses utilized week-96 data from STARTMRK (MK-0518 Protocol 021; NCT00369941), BENCHMRK-1 (MK-0518 Protocol 018; NCT00293267) and BENCHMRK-2 (MK-0518 Protocol 019; NCT00293254).