OBJECTIVES: A decision-analytic Markov model was developed to predict the health outcomes of using sofosbuvir (SOF) -based regimen compared with current treatment options for patients who are co-infected with hepatitis C (HCV) and HIV.  METHODS: The analysis modeled a cohort of treatment-naïve genotype 1 patients co-infected with HIV and HCV with a mean age of 54 years and 25% with cirrhosis.  The model was evaluated from a US third-party payer perspective for a lifetime time horizon.  SOF+pegylated interferon + ribavirin (PR) for 12 weeks was compared with telaprevir (TVR)+PR for 48 weeks, and boceprevir (BOC)+PR for 48 weeks. Sustained virologic response (SVR) rates were derived from clinical trials conducted in the HCV/HIV co-infected patient population. Transition probability, utility, and cost estimates were based on a literature review, public sources, and consensus by a panel of 4 hepatologists. RESULTS: In the HCV/HIV co-infected cohort, the SOF-based regimen was associated with the lowest incidence of liver disease complications including hepatocellular carcinoma, decompensated cirrhosis, need for liver transplantation, and HCV-related death (reduction of 52% compared to TVR+PR and 65% compared to BOC+PR). In addition, patients receiving SOF+PR experienced more quality-adjusted life-years (QALYs), compared to those treated with other options (ranged from 0.63 to 1.10 QALYs).  In terms of incremental quality adjusted life years gained, SOF+PR dominated over TVR+PR and BOC+PR.  The sensitivity analysis indicated that the results were robust to changes in model inputs and assumptions, such as SVR rates, adverse event incidence, costs for treatment monitoring and management of adverse events, and transition probability estimates. CONCLUSIONS: The SOF-based regimen of shorter duration, improved tolerability profile and high SVR rates was projected to yield the most favorable health and economic outcomes in the genotype 1 HIV and HCV co-infected population compared to current treatment regimens using telaprevir or boceprevir.