Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs.
Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug-drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176-890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6-14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT.
Tricot
L
L
Hôpital Foch, Suresnes, France. l.tricot@hopital-foch.org
Teicher
E
E
Peytavin
G
G
Zucman
D
D
Conti
F
F
Calmus
Y
Y
Barrou
B
B
Duvivier
C
C
Fontaine
C
C
Welker
Y
Y
Billy
C
C
de Truchis
P
P
Delahousse
M
M
Vittecoq
D
D
Salmon-Céron
D
D
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D016572:Cyclosporine; D019427:HIV Integrase; D016559:Tacrolimus; C514801:p31 integrase protein, Human immunodeficiency virus 1