*Purpose: Trials describing 4-12 week courses of direct-acting anti-viral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants), may be limited in application by costs and delayed access to expensive DAAs. A short prophylactic strategy may be safer and cost-effective. We report a cost-effectiveness analysis using the payer perspective to determine the least expensive DAA regimen, using published strategies.

*Methods: Cost analyses comparing four strategies: 1) Seven-day DAA prophylaxis using generic Sofusbuvir/Velpatasvir (SOF/VEL) followed by a full course 12-week branded Glecapravir/Pibrentasvir (G/P) for those with HCV transmission (base case HCV infection rate: 4%; sensitivity analysis range: 1% – 13%); 2) Eight-day DAA prophylaxis using branded G/P followed by a full course 12-week branded SOF/VEL/VOX (voxilaprevir) for those with HCV transmission (base case HCV infection rate: 0%; sensitivity analysis range: 0% – 4%); 3) Four-week peri-operative DAA prophylaxis using generic SOF/VEL followed by 12-week branded G/P for those with HCV transmission (base case HCV infection rate: 0%; sensitivity analysis range: 0% – 1%); and 4) ‘Transmit-and-treat’ strategy with 8-weeks of G/P (assuming 100% transmission rate). The probabilities and costs (base case value and range; costs in 2020 US$) used in the model were estimated using current data from clinical trials and public databases. A decision tree was constructed to compare expected costs of each option, using a 6-month time frame. One-way sensitivity and threshold analyses were performed to account for uncertainty in the variable estimates for the two less expensive treatment options. All modeling and analyses were performed in TreeAge Pro Healthcare 2020.

*Results: Cost analyses comparing strategies, showed that in the base case model, Strategy 1 was the least expensive (7-day SOF/VEL prophylaxis) with an expected cost of US $2,962, followed by Strategy 2 (8-day G/P prophylaxis; expected cost: $3,756), Strategy 3 (4-week SOF/VEL prophylaxis; expected cost: $5,538), and then Strategy 4 (8-week G/P treatment; expected cost: $26,294). The threshold value for Strategy 1 and 3 to break-even in expected cost was when the probability of infection with 7-day prophylaxis (SOF/VEL) equals 10.5%, when the daily cost of SOF/VEL equals $75.13, or when the daily cost of G/P equals $1,236.13. The threshold value for Strategy 1 and 2 to break-even in expected cost was when the probability of infection with 7-day prophylaxis (SOF/VEL) equals 6%, when the daily cost of SOF/VEL equals $311.24, or when the daily cost of G/P equals $298.38.

*Conclusions: Short duration DAA prophylaxis using either 7 days of SOF/VEL or 8 days of G/P is more cost-effective than 4 weeks of SOF/VEL or 8 weeks of G/P and has the potential of resulting in significant cost-savings in a majority of D+/R- transplants.

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