Drug-specific T cells in an HIV-positive patient with nevirapine-induced hepatitis.
BACKGROUND
Nevirapine is associated with idiosyncratic reactions such as skin rash, hepatitis and hypersensitivity syndrome, which have the hallmarks of being immune mediated. However, there is little laboratory evidence to support an immune pathogenesis.


METHODS
A HIV-positive individual who developed hepatitis within 6 weeks of starting nevirapine, in the absence of any cutaneous manifestations, is described. Other causes of hepatitis were excluded, and the patients liver function normalized on withdrawal of nevirapine. Lymphocytes from the patient, and six individuals with HIV who were on nevirapine without adverse effects, were exposed to nevirapine and its metabolites, and lymphocyte proliferation assessed by 3H-thymidine incorporation on day 5.


RESULTS
The T cells taken from the nevirapine-hypersensitive patient proliferated in the presence of nevirapine with a stimulation index of greater than 2. There was no proliferation with nevirapine metabolites. T cells taken from HIV-positive control individuals showed no proliferation with either nevirapine or its metabolites.


CONCLUSIONS
The results from our patient suggest that T cells may be involved in the pathogenesis of nevirapine-induced hepatitis. Larger numbers of patients need to be studied to fully evaluate the role of T cells in nevirapine-induced hepatitis and nevirapine hypersensitivity syndrome.
Drummond
Nicola S
NS
Department of Pharmacology and Therapeutics, The University of Liverpool, Ashton Street, Liverpool, UK.
Vilar
F Javier
FJ
Naisbitt
Dean J
DJ
Hanson
Anita
A
Woods
Anthony
A
Park
B Kevin
BK
Pirmohamed
Munir
M
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D006679:HIV Seropositivity / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000276:immunology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine