Convergence of geographic regions endemic for human immunodeficiency virus (HIV) and cutaneous leishmaniasis (CL) raise concerns that HIV co-infection may worsen CL burden, complicating already lengthy and costly CL treatments and highlighting a need for newer therapies. We constructed two Markov decision models to quantify impact of HIV on CL and help establish a target product profile for new CL treatments, accounting for co-infection. The HIV co-infection increased lifetime cost per CL case 11-371 times ($1,349-45,683) that of HIV-negative individuals ($123) and Brazil's CL burden from $1.6-16.0 million to $1.6-65.5 million. A new treatment could be a cost saving at ≤ $254 across several ranges (treatments seeking probabilities, side effect risks, cure rates) and continues to save costs up to $508 across treatment-seeking probabilities with a drug cure rate of ≥ 50%. The HIV co-infection can increase CL burden, suggesting more joint HIV and CL surveillance and control efforts are needed.