Drug specific t-cell responses in hiv patients with clinical drug hypersensitivity

Abstract

Introduction: HIV patients have a higher risk of drug allergy than general population. Nevirapine (NVP) is one of the commonly prescribed NNRTIs in Thailand and other developing countries. Approximately 20% of patients developed NVP-rash, 2-5% have hypersensitivity reaction (fever, rash, hepatitis) and approximately 0.3% have Steven-Johnson syndrome or TEN. Multiple drug exposure in advanced immunocompromised patients has made the diagnosis of allergy to what specific drug is much more challenging. There is no any gold standard test to assist the diagnosis, thus we examined a flowcytometry-based drug-specific T cell assay and whether by adding MDCs will enhance the sensitivity of this T cell assay. Methods: Peripheral blood mononuclear cell (PBMC) samples from 8 HIV-infected patients who had clinical allergic to nevirapine (median duration after NVP-allergy is 31 months, range 1-99 months) and from 10 control healthy donor and from other 10 HIV+ patients subjects who were treated with nevirapine with no clinical hypersensitivity were tested in vitro for NVP-induced CD134+/CD25+ upregulation of CD4+ T cells. The assays were also compared between adding or not adding MDCs as antigen presentation on the sensitivity of the responses to NVP. Results: With and without MDCs added, NVP induced positive CD134+/CD25+/CD4+ responses only 7/10 (70%) vs 1/10 (10%) (P=0.003), respectively. Conclusion: Although other drug-specific T cell in vitro tests such as CD69, CD107a, cytokines have been investigated to diagnose T-cell mediated drug allergy, this is the first evidence to support the potential role of CD134 or OX40 expression in drug-specific T cells. In addition our results have also supported the previous report of the useful role of MDCs to enhance the sensitivity of in vitro drug-specific T cell test particularly in patients who have history of the specific drug allergy for years.