Optimizing Tacrolimus Target Trough Levels in Organ Transplantation Among Patients Living With HIV Receiving Antiretroviral Therapy

BACKGROUND: Solid organ transplantation (SOT) in patients living with HIV (PLWH) has transitioned from a relative contraindication to standard practice following the widespread use of effective antiretroviral therapy (ART). Although patient and graft survival increasingly parallel those of HIV-negative recipients, optimizing immunosuppressive therapy-particularly tacrolimus-remains a major clinical challenge in this population. OBJECTIVES: This review examines the mechanisms and clinical consequences of ART-tacrolimus drug-drug interactions, evaluates the role of therapeutic drug monitoring (TDM), and highlights emerging strategies to improve attainment of target tacrolimus trough levels in PLWH undergoing transplantation. CONTENTS: Tacrolimus has a narrow therapeutic index and is highly susceptible to cytochrome P450 3A4-mediated interactions with ART, especially protease inhibitor- and cobicistat-based regimens. These interactions often necessitate extreme dose reductions, result in marked pharmacokinetic variability, and complicate maintenance of stable trough concentrations. Subtherapeutic exposure is associated with increased rejection risk, whereas supratherapeutic levels increase nephrotoxicity and infection. While integrase strand transfer inhibitor-based regimens reduce interaction burden, many PLWH remain on boosted ART, underscoring the importance of intensive TDM. This review also discusses tacrolimus formulation choice as a modifiable factor, with growing evidence supporting liquid tacrolimus to enable micro-dose titration and improve time in therapeutic range. Emerging pharmacometric approaches, including population pharmacokinetic modeling and Bayesian dosing, offer additional opportunities for precision immunosuppression. IMPLICATIONS: Optimizing tacrolimus exposure-rather than HIV status itself-is central to transplant outcomes in PLWH. Integrating ART-informed dosing, formulation flexibility, and advanced TDM strategies may reduce variability, improve graft outcomes, and inform future guideline development for this expanding transplant population.