Dolutegravir-Based Antiretroviral Regimens for HIV Liver Transplant Patients in Real-Life Settings

Abstract

Background and Objectives Liver transplantation is now considered a safe procedure in patients with HIV because of the advent of potent antiretroviral therapies (ART). Objective We aimed to describe the use of dolutegravir-based maintenance ART in patients with HIV and liver transplant regularly followed in our hospital. Methods We searched the database of our Department of Infectious Diseases for liver transplant recipients receiving calcineurin inhibitor-based maintenance immunosuppression concomitantly treated with dolutegravir for at least 1 month. Results Ten HIV-positive liver transplant recipients were identified. At 4.6 ± 3.5 years post-transplant, all the patients were switched to dolutegravir-based therapies for treatment simplification. However, at 1 year after the switch, five of the ten patients returned to their previous ART regimens because of increased serum transaminases (n = 1), reversible increased serum creatinine (n = 4), repeated episodes of nausea/vomiting (n = 1) and variable out-of-range concentrations of tacrolimus or cyclosporine (n = 2). However, it should be recognized that these events cannot be unequivocally ascribed to dolutegravir and, in the case of increased serum creatinine, are predictable. Conclusions The management of HIV-positive liver transplant recipients in clinical practice is a complex task, where possibility of simplifying antiretroviral regimens must be balanced with the need to guarantee optimal immunosuppression and the finest treatment tolerability. A multidisciplinary approach involving physicians and clinical pharmacologists/pharmacists could help achieve this goal.

Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review

“… 39 More data will be required to determine which InSTI provides the best efficacy, safety, and tolerability profile in this subpopulation. 40 In this regard, an ongoing study aims to evaluate the feasibility of switching HIV-infected kidney transplant recipients to a 3-drug fixed-dose combination containing bictegravir, tenofovir alafenamide, and emtricitabine (NCT04530630).…”

Non-nucleoside structured compounds with antiviral activity—past 10 years (2010–2020)

“…One of the examples of HIV integrase inhibitors is dolutegravir sodium (sodium; (3S,7R)-13-[(2,4-difluorophenyl)methylcarbamoyl]-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-10,13-dien-11-olate) (trade name Tivicay™, Table 2 ), a second-generation integrase inhibitor approved by FDA in 2013 in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients. Dolutegravir is also an attractive option for HIV-positive liver transplant recipients because of its minimal dependence on cytochrome P450 (CYP)-3A-mediated metabolism, high potency, and high genetic barrier [ 97 ].…”