Enfuvirtide: a safe and effective antiretroviral agent for human immunodeficiency virus-infected patients shortly after liver transplantation.
The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV)-coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir-exposed patients. During period 1, tacrolimus and cyclosporine A doses were 8 and 600 mg/day, respectively, and the trough concentrations were within the therapeutic range in both groups. In period 2, the addition of lopinavir/ritonavir to the immunosuppressant regimen enabled a reduction in the dose of immunosuppressants required to maintain trough concentrations within the therapeutic range (to 0.3 mg/day for tacrolimus and 75 mg/day for cyclosporine). Immunosuppressant doses were not modified by the reintroduction of enfuvirtide, there being no change in the mean trough concentrations over the 3 periods. CD4 cell counts remained at about 200 cells/mm3. The HIV RNA viral load remained undetectable. Both groups displayed signs of mild cytolysis and cholestasis due to the recurrence of HCV, whereas no renal insufficiency was observed. Enfuvirtide is an attractive alternative to standard ARV therapy, facilitating the management of drug-drug interactions shortly after liver transplantation. Moreover, the lack of liver toxicity renders this drug valuable in the event of a severe HCV recurrence.
Département Médecine Interne et Infectiologie, AP-HP Hôpital Paul Brousse, Villejuif, France. elina.teicher@pbr.aphp.fr
Elina
E
Teicher
Chadi
C
Abbara
Jean-Charles
JC
Duclos-Vallée
Teresa
T
Antonini
Laurence
L
Bonhomme-Faivre
Delphine
D
Desbois
Didier
D
Samuel
Daniel
D
Vittecoq
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017093:Liver Failure / Q000150:complications* / Q000628:therapy*; D016031:Liver Transplantation / Q000379:methods*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D015700:HIV Envelope Protein gp41; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011744:Pyrimidinones; D000077560:Enfuvirtide; D061466:Lopinavir; D016572:Cyclosporine; D019438:Ritonavir; D016559:Tacrolimus