Life-threatening interaction between antiretroviral therapy and vinblastine in HIV-associated multicentric Castleman's disease

: Background: HIV-infected patients still present a high risk of developing lymphoproliferative malignancies, despite the fact that their prognosis has been considerably improved by highly active antiretroviral therapy (HAART). Potential interactions exist between antiretroviral drugs, in particular protease inhibitors, and anti-neoplastic ones, but their impact in terms of clinical and haematological adverse events remains unclear. Methods: We report a case of potentially life-threatening interaction between vinblastine and antiretroviral therapy in a patient presenting with HIV-associated multicentric Castleman's disease (MCD). Results: A 55-year-old HIV-1 infected patient was diagnosed with MCD while being treated with a salvage HAART regimen consisting of zidovudine, lamivudine, abacavir, nevirapine and ritonavir-boosted lopinavir. Vinblastine was prescribed as a monotherapy at the usual dose of 6 mg/m2 (i.e. 10 mg) every 3 weeks. The first vinblastine course was performed without HAART with no adverse event. Antiretroviral therapy was resumed for the two following courses which were associated with unexpected severe digestive and haematological toxicities, and moderate renal failure. Vinblastine was then administered alone at increasing doses without toxicity. HAART was finally resumed and we assessed that a decreased vinblastine dose of 2 mg/m2 was well tolerated, with a complete response of MCD. Conclusions: HAART regimen comprising protease inhibitors, which are potent inhibitors of cytochrome P450 and P-gp, could interfere with anti-neoplastic drugs, as demonstrated with vinblastine in our case report.