ritonavir and Hematologic-Diseases

The incidence of Hodgkin lymphoma (HL) is rising among individuals infected with human immunodeficiency virus (HIV). Standard treatment regimens include vinblastine, which is known to cause neurotoxicity (NT) and is metabolized by cytochrome 3A4 (CYP3A4). This is inhibited by protease inhibitors (PIs), possibly increasing vinblastine exposure. There is little information on how interactions affect clinical outcome. A retrospective review of 32 patients with HIV-HL receiving chemotherapy with curative intent was performed to identify the frequency and risk factors for NT, hematologic toxicity (HT) and lung toxicity (LT). Treatment was: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in 90%, MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vinblastine) in 10% and HAART (highly active anti-retroviral therapy) in 63%. Seventeen potential risk factors and 18 individual anti-retroviral (ARV) agents were examined, and only ritonavir or lopinavir use was found to have a significant association with toxicity. Grade 3-4 NT occurred in five patients, grade 3-4 HT in 17, infectious complications in 10 and bleomycin LT in three. Ritonavir and lopinavir use was associated with grade 3-4 NT (p = 0.03 and p = 0.01, respectively), and ritonavir with any HT (p = 0.04). Patients with HIV-HL experienced an increased incidence of NT and possibly HT. The use of ritonavir or lopinavir was associated with NT, suggesting a clinically significant interaction with vinblastine. Prospective pharmacokinetic studies to devise a rational dosing strategy for vinblastine in patients receiving ritonavir/lopinavir are warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Dacarbazine; Doxorubicin; Female; Hematologic Diseases; HIV Infections; HIV Protease Inhibitors; Hodgkin Disease; Humans; Incidence; Kaplan-Meier Estimate; Lopinavir; Lung Diseases; Male; Mechlorethamine; Middle Aged; Nervous System Diseases; Prednisone; Procarbazine; Prognosis; Retrospective Studies; Ritonavir; Vinblastine; Vincristine