Cellular Antigen Stimulation Test (CAST) as a Novel, Affordable Laboratory Technique to Assess Potential Hypersensitivity to All Available Antiretroviral Compounds

Recently,novel allergometric techniques allow to test inhalants,food,and also drugs by specific in vitro assays. A flow cytometry technique based on the search of sulphidoleukotrienes LCT4, LTD4 and LTE4 released by basophils stimulated in vitro by IL-3 in presence of the examined antigens (cellular antigen stimulation test,or CAST), has a 80—90% sensitivity-specificity rate,and becomes particularly useful when prick tests are not applicable, and allergic reactions are not mediated by allergen-specific IgE immunoglobulins.Methods-Results: During the past three years, 13 HIV-infected subjects (eight females and five males, aged 37—52 years),underwent a standardized, specific in vitro cellular antigen stimulation test (CAST),due to serious cutaneous (six cases),systemic (two patients), and combined cutaneous-systemic hypersensitivity reactions (five subjects),apparently not elicited by the introduction of abacavir and nevirapine (which are the antiretroviral agents burdened by the greatest frequency of expected early allergic reactions,mediated by already recognized pathogenetic mechanisms). Based on the results of CAST testing, an allergic intolerance to ritonavir (six cases), lopinavir,nelfinavir, and didanosine (three cases each), saquinavir and lamivudine (two cases), and fosamprenavir,zidovudine, zalcitabine, stavudine, and efavirenz (one case each), was documented: in 10 cases out of 13 (76.9.5%) multiple intolerances were detected. A perfect relationship was documented between the results of CAST testing and the panel of combined antiretroviral compounds recently experienced by each allergic patient,and a CASTbased elimination of in vitro allergenic molecules allowed a rapid introduction of another effective antiretroviral combination. Conclusions: Adverse events to antiretroviral drugs are quite frequent among HIV-infected patients, compared with the general population. Further,controlled studies are needed to implement in vitro allergometric testing in patients treated for HIV infection,who are exposed to unpredictable drug intolerance reactions. In fact,HIV-infected subjects may suffer from frequent allergic drug reactions which may be difficult to be systematically recognized (due to the frequent,multiple concurrent pharmacotherapy, and the combined antiretroviral therapy itself).