Clinical relevance of cross-reactivity between darunavir and trimethoprim-sulfamethoxazole in HIV-infected patients
Journal
AIDS
Journal Volume
29
Journal Issue
16
Pages
2213-2214
Date Issued
2015
Author(s)
Abstract
HIV-positive patients receiving darunavir/ritonavir (DRV/RTV)-based therapy are given a warning for potential cross-reactivity with sulfonamide-containing drugs, such as trimethoprim-sulfamethoxazole (TMP-SMX), without substantial clinical evidence [1]. The recent retrospective cohort study conducted by Buijs et al.[2], with a large number of HIV-positive patients with exposure to DRV/RTV and TMP-SMX (n = 405), addressed the issue of whether this cross-reactivity exists between DRV/RTV and TMP-SMX. Although DRV/RTV-related rashes were infrequently seen (2.0%) in this cohort, patients with TMP-SMX allergy were at higher risk for DRV/RTV-related rash compared with those without [5.1% vs. 1.2%; odds ratio (OR) 4.29, 95% confidence interval (CI) 1.05–17.56]. However, the small case number of patients with an allergy to DRV/RTV precluded further multivariate analysis. The previous Asian studies performed by ourselves [3] and Nishijima et al.[4] revealed a higher rate (10%) of DRV/RTV-related rashes among patients receiving DRV/RTV (800/100 mg) with or without a history of exposure to TMP-SMX. Different inclusion criteria used to conduct studies among populations of different ethnicities make comparisons among these studies difficult. In our study [3], a total of 74 patients received both TMP-SMX and DRV/RTV, and 12 patients had an allergy to TMP-SMX and 62 patients did not. According to the Naranjo probability scale [5], a probable DRV/RTV allergy was observed in one patient (8.3%) with a TMP-SMX allergy compared with two patients (3.2%) without a TMP-SMX allergy (P = 0.42). The pooling of probable and possible cases showed that DRV/RTV allergy was found in one patient (8.3%) with a TMP-SMX allergy compared with four patients without a TMP-SMX allergy (6.5%) (P = 0.99). Nishijima et al.[4] reported a lower rate of DRV/RTV-related rash in patients with a TMP-SMX allergy than that without a TMP-SMX allergy (6.5% vs. 10.3%; P = 0.55). Limited by the small sample size, both Asian studies that excluded patients receiving a higher dose of DRV/RTV (1200/200 mg) failed to conclusively demonstrate any statistically significant cross-reactivity between TMP-SMX and DRV/RTV. While Buijs et al.[2] concluded that DRV allergy was rarely of clinical relevance based on the results of low rate of DRV/RTV-related rashes and cross-reactivity with TMP-SMX in the large cohort, a high proportion of discontinuation due to allergy among patients with DRV/RTV-related rashes was noted (4/8; 50.0%), which was also observed in our study (20/26; 76.9%). Among the 26 patients with DRV/RTV-related rashes in our study [3], 11 patients (42.3%) were treated with oral antihistamine or steroids without benefit before discontinuation of DRV/RTV. In the other 15 patients who were not treated with oral antihistamine or steroids, eight patients had generalized skin rashes, and DRV/RTV was discontinued immediately for the sake of higher severity (Fig. 1) and concerns about Stevens–Johnson syndrome. Our findings suggest that, though cross-reactivity between TMP-SMX and DRV/RTV is infrequent, clinical vigilance remains warranted.Fig. 1: Skin rashes in patients with an allergy to boosted darunavir.Acknowledgements Conflicts of interest C.-C.H. has received research support from Janssen and speaker honoraria from Bristol-Myers Squibb and Gilead, and served on advisory boards for Gilead. K.-Y.L. has no conflicts of interest to declare.
Other Subjects
antihistaminic agent; darunavir; ritonavir; steroid; sulfamethoxazole; trimethoprim; anti human immunodeficiency virus agent; antiinfective agent; cotrimoxazole; darunavir; cross reaction; disease severity; drug hypersensitivity; human; Human immunodeficiency virus infected patient; Human immunodeficiency virus infection; Letter; priority journal; rash; adverse drug reaction; Bacterial Infections; complication; drug hypersensitivity; drug interaction; HIV Infections; metabolism; pathology; retrospective study; Anti-Bacterial Agents; Anti-HIV Agents; Bacterial Infections; Darunavir; Drug Hypersensitivity; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
Publisher
Lippincott Williams and Wilkins
Type
letter