Results

1. A case of upregulated Cyclosporin-A catabolism in a HIV-1+/HCV+hemophiliac after liver transplantation and Efavirenz treatment • Canbay1, R. Gieseler2, K. Radecke1, M. Kullmer1, B.Ross1, C. Valentin-Gamazo3,U. Treichel1 , and G. Gerken1 • 1 Dept of Gastroenterology and Hepatology, 3 Dept. of General Surgery and Transplantation Medicine, Universiy Clinic Essen, and 2LTBH Medical Research Institute, Beverly Hills, CA, USA Background HCV-related liver cirrhosis is a leading cause of morbidity and mortality in hemophili-acs. To date, orthotopic liver transplantation (OLT) is the only potential cure – and particularly in patients actively treated for co-infection with HIV-1, careful monitoring of immunosuppressive drugs is required. Patient A thirty-six-year old male haemophliac co-infected with HIV-1 and HCV. Prior to OLT, the patient had 278 CD4+ T cells/ml and < 50 HIV-1 RNA copies/ml. Three days after receiving a liver allograft, his pre-surgical anti-retrovirals (d4T/3TC) were re-sumed. Two weeks post transplantation, Efavirenz (EFV) was instituted at a single dosage of 600 mg/day. The patient was immunosuppressed with cyclosporin-A (CsA) at 300 mg/day. Results Before EFV was firstly given on day +14 after OLT, the CsA level was 244 ng/ml. After instituting EFV, the levels of CsA and its metabolites decreased rapidly. On day +15, the CsA concentration was moderately decreased to 230 ng/ml and dropped to 215 ng/ml on day +16. The most pronounced decrease was observed on day +18 with CsA at 149 ng/ml. To counteract the danger of graft rejection, the CsA dosage was increased at this time to 400 mg/day and concentrations of CsA and its assay-detectable metabolites increased to 191 ng/ml (day +19), 203 ng/ml (day +20), and 186 ng/ml (day +21). CsA was thus re-adjusted to the efficacious immunosuppressive drug concentration. In contrast, EFV levels remained in the therapeutic range throughout the period of observation. Conclusions It is established fact that p450 cytochromes, especially those belonging to the family CyP 3A, metabolize CsA via mono- or dihydroxylation as well as N-methylation. How-ever, EFV not only acts as a non-competitive inhibitor of the HIV-1 reverse transcript-ase, but is also known as an inducer of the family member CyP 3A4. Our results there-fore suggest that EFV may enhance the catabolism of CsA via interaction of these two agents (while d4T and 3TC). By increasing the CsA dosage, acute graft rejection was prevented, thus allowing for continued anti-HIV-1 treatment post transplantation with combination EFV/d4T/3TC, and maintenance of undetectable HIV-1 RNA (< 50 copies/ml).