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Objectives Nirmatrelvir/ritonavir may cause a clinically relevant drug-drug interaction (DDI) with immunosuppressive drugs, such as tacrolimus, which may condition the use of this antiviral in transplant patients. We aimed to describe the management of this interaction. Methods Descriptive study in which renal transplant patients in treatment with nirmatrelvir/ritonavir and tacrolimus were included. They suspended tacrolimus the day before starting the antiviral treatment, and the decision to restart it was made based on their tacrolimus blood levels. Main variables studied to measure this DDI were tacrolimus blood concentration, dose adjustment and serum creatinine. Results Three patients were included. During the study, tacrolimus levels elevation did not have repercussion in the serum creatinine, that remained stable in all patients. No patient required hospitalisation or showed signs of rejection.Conclusions Our experience provides further evidence that this interaction should not be a contraindication to treatment with nirmatrelvir/ritonavir, and can be managed with close monitoring of tacrolimus levels.

BackgroundDolutegravir (DTG), a second-generation integrase strand transfer inhibitor (INSTI), is currently among the most commonly used antiretroviral agents. Recent reports have raised concerns about their safety, especially with regard to neuropsychiatric adverse effects (neuropsychiatric AEs).PurposeTo assess the neurotoxicity associated with DTG in the treatment of human immunodeficiency virus infected patients (HIV +).To compare our results with those published in recent reports.Material and methodsWe performed a descriptive, retrospective and observational study in which all HIV +patients treated with DTG were enrolled between January 2015 and September 2017. Demographic, analytical and clinical data were collected in EXCEL® 2013: age, sex, adverse effects (AEs), antiretroviral therapy (ART) and reasons for discontinuation, from the Digital Clinical History (Diraya) and FarmaTools® software.ResultsDuring the study period, 292 patients initiated ART containing DTG. Treatment was discontinued in 16.78% (median age 59 years (26–87), 65.3% males). Of these, 79.5% were in concomitant ART with abacavir/lamivudine (ABC/3TC), 10.2% with tenofovir/emtricitabine (TDF/FTC), 4% with etravirine (ETR) and the remaining ones with potentiated protease inhibitors.Most of the patients (85.7%) discontinued treatment during the first year. In 18 patients (36.7%) the reason for DTG discontinuation was neuropsychiatric AEs: insomnia (55.5%), anxiety, asthaenia and nervousness (22.2% respectively), dizziness (11.1%) and, less frequently, paranoid ideas and nightmares (5.6%).Neuropsychiatric AEs were more frequent in females (53%) than in males (28.1%), with a median age of 51 years (34–87). Neurotoxicity was reversible in 100% of patients when DTG was discontinued and more frequentl in those receiving concomitant treatment with ABC/3TC (83.3%).ConclusionEarly discontinuation of dolutegravir from neurotoxicity was frequent, mainly in females and in patients who initiated abacavir/lamivudine at the same time, but not in elderly patients. Therefore, our results agree with those already published in recent reports. As dolutegravir is one of the most commonly used antiretroviral options both in naive and pretreated patients, further research on their safety and neurotoxicity mechanisms are needed.Reference and/or Acknowledgements1. Hoffmann C, Welz T, Sabranski M, Kolb M, Wolf E, StellbrinkHJ, Wyen C. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med2017;18:56–63.No conflict of interest

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