Patients with human immunodeficiency virus (HIV) most often have hepatitis C virus (HCV) or hepatitis B (HBV) virus coinfection, or both, as a cause of their liver disease. Recent survival statistics show that patients infected with HIV treated with highly active antiretroviral therapy (HAART) can expect a significant prolongationof life by interfering with the natural progression of HIV to aquired immune deficiency syndrome (AIDS). Therefore, HIV-positive patients experiencing complications of liver failure are at greater immediate risk of dying from their end-stage liver disease (ESLD) rather than their HIV. Many transplant centers still consider HIV infection asa contraindication for orthotopic liver transplantation (OLT). Atour two institutions, we believe that patients with HIV suffering from ESLDshould be considered for OLT. This study evaluates the survival of patients undergoing OLT with HIV under HAART therapy. OLT was performed in 16 patients with HIV suffering from ESLD as a result of chronic HCV, chronic HBV, or fulminant hepatic failure (FHF). Collected data include patient demographics, patient and graft survival, pre-OLT assessments, and postoperative complications (including opportunistic infections). Ten patients at Pittsburgh and 6 patients at Miami received OLT. Of the 16 patients who received OLT, 14 remain alive to date. Thirteen of 16 patients are more than 12 months post-OLT, whereas the last patient is currently 6 months post-OLT. Five patients at Miami and 9 of 10 patients at Pittsburgh received HAART therapy before OLT, although 2 of the Pittsburgh patients had their HAART therapy discontinued before OLT because of significant liver dysfunction. The pre-OLT viral loads were undetectable in 13 of 16 patients. The cluster determinant (CD)4 count was less than 200 in 6 patients and greater than 100 in 2 patients before OLT. In all patients, CD4 counts increased above 200 in the post-OLT period. Tacrolimus toxicity associated with the pharmacologic inhibition of cytochrome p450 metabolism caused by protease inhibitors occurred in 6 patientsafter OLT. Six patients (38%) experienced acute cellular rejection immediately after OLT. Our experience suggests that OLT is effective in selected HIV-positive patients suffering from ESLD. Patient and graftsurvival was similar to non–HIV-positive patients suffering from the same indications for OLT. Acute cellular rejection was no less frequent that seen in non–HIV-positive patients. Given the complex pharmacologic interactions between the protease inhibitors and tacrolimus, careful monitoring, and attention is required to prevent toxicity or underdosing.