Objective: Both darunavir (DRV) and trimethoprim-sulfamethoxazole (TMP-SMX) carry a sulfonamide moiety and a warning for this cross-reactivity is given in the label of DRV. The aim of this study was to investigate the potential cross-reactivity between both drugs. Design: Retrospective cohort study with a nested case-control study. Methods: HIV-infected patients that received DRV-containing antiretroviral therapy at any time during the period of their HIV infection were included. Patients with

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... o history of TMP-SMX use were excluded. The incidence of a DRV allergy, according to the Naranjo probability scale, was investigated in patients with an allergy to TMP-SMX compared with those without such an allergy. In order to identify possible risk factors associated with a DRV allergy among patients allergic to TMP-SMX, a nested casecontrol study was subsequently performed. Results: A total of 405 patients were included, of whom 79 (17.5%) had a history of allergy to TMP-SMX. A DRV allergy was seen in four patients (5.1%) with a TMP-SMX allergy compared with four (1.2%) without a TMP-SMX allergy (P ¼ 0.05). Patients with a TMP-SMX allergy were at higher risk for a DRV allergy (odds ratio 4.29; 95% confidence interval, 1.05-17.56). No additional risk factors for a DRV allergy among patients allergic to TMP-SMX were identified in the nested case-control study. Conclusion: Although DRV allergy is uncommon, making cross-reactivity with TMP-SMX a rare clinical problem, it appears to exist more often in the background of a TMP-SMX allergy.