Perioperative pharmacokinetics of lenacapavir during massive hemorrhage in a patient with hemophilia a undergoing liver transplantation.

Lenacapavir (LEN) is a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months; however, its pharmacokinetic behavior during massive hemorrhage is unknown. We report a man in his 60s with multidrug-resistant HIV-1 infection and severe hemophilia A who underwent living-donor liver transplantation for HCV-related hepatocellular carcinoma. After a 2-week oral loading phase, LEN (927 mg) was administered four weeks before surgery. Liver transplantation was performed with intraoperative blood loss of 7046 g, approximately 1.5 times the estimated circulating blood volume. Despite this massive hemorrhagic stress, plasma LEN concentrations were 59.9 ng/mL on the day of surgery and 57.3 ng/mL on postoperative day 1, showing minimal change without additional dosing. Twenty-four weeks after the first injection, immediately before the second scheduled dose, plasma LEN concentration remained adequate at 80.8 ng/mL. HIV-1 RNA remained suppressed below 20 copies/mL throughout the clinical course. To our knowledge, this is the first report describing perioperative LEN pharmacokinetics during massive blood loss. These findings indicate that LEN exposure may remain stable despite substantial intravascular volume depletion, supporting the pharmacokinetic robustness of long-acting antiretroviral therapy in major surgical settings.