Date of report 17 Mar 2026
Reported case interaction between
Ritonavir and Risperidone
Ritonavir and Risperidone
Drugs suspected to be involved in the DDI
Complete list of drugs taken by the patient
Risperidone; Lamotrigine; Levomepromazine
Clinical case description
A 19-year-old cisgender male with a history of depression and prior suicide attempts was diagnosed with HIV infection. At diagnosis, HIV viral load was 212,000 copies/mL (log 5.3) and CD4 count was 291 cells/mm³ (12%). Antiretroviral therapy (ART) with doravirine/tenofovir disoproxil fumarate/lamivudine was initiated.
The patient demonstrated poor adherence and experienced virological failure despite multiple adherence reinforcement interventions, with a viral load of 1,300 copies/mL. Resistance testing could not be performed due to non-amplifiable samples. In the absence of alternative options, ART was empirically switched to darunavir/ritonavir plus tenofovir disoproxil fumarate/lamivudine. Following this change, the patient achieved virological suppression.
In March 2025, the patient was hospitalized and diagnosed with schizophrenia. Treatment with risperidone, lamotrigine, and levomepromazine was initiated.
One month later, given the potential for drug–drug interactions with the psychiatric regimen, and in the context of psychiatric stabilization, ART was switched to bictegravir/tenofovir alafenamide/emtricitabine.
Clinical Outcome
Editorial Comment
This case highlights the potential for drug–drug interactions between risperidone and ritonavir-boosted protease inhibitors such as darunavir/ritonavir. Risperidone is primarily metabolized by CYP2D6 and, to a lesser extent, by CYP3A4. Ritonavir is a potent inhibitor of CYP3A4 and may also affect CYP2D6, potentially increasing risperidone plasma concentrations.
Therefore, coadministration should be approached with caution, and dose adjustments of risperidone may be required. Several case reports have described adverse effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, and angioedema in similar contexts.
Although no adverse events were observed in this case, the short duration of concomitant use may have limited the clinical impact of the interaction. Nonetheless, caution is warranted when these drugs are used together. Close clinical monitoring, consideration of alternative antiretroviral regimens, and potential dose adjustments of risperidone should be considered, particularly in patients receiving long-term boosted protease inhibitor therapy.
University of Liverpool Recommendation
Potential interaction - may require close monitoring, alteration of drug dosage or timing of administration
Personal information from the specialist
Other authors