Protease inhibitors potentiate chemotherapy-induced neutropenia

Pharmacokinetic interactions between chemotherapy and highly active anti-retroviral therapy (HAART) are described, but there are few data on their clinical relevance. Patients with systemic AIDS-related non-Hodgkin lymphoma (ARL) were treated with concomitant HAART and infusional cyclophosphamide-doxorubicinetoposide (CDE) chemotherapy. We compared neutropenia according to whether patients received protease inhibitor (PI)based HAART or non-PI regimens. Differences in survival, response rates, immunologic parameters, and virologic parameters were also investigated. The day-10 (Mann-Whitney U test; P =.012) and day-14 (P =.025) neutrophil counts were significantly lower in patients receiving Pls, though there were no differences in the number of days of granulocyte colony-stimulating factor (G-CSF) administered between groups (P =.16). Grade 3 or 4 infections requiring hospitalization were recorded for a total of 58 (31%) of 190 cycles of CDE: 23 (48%) of 48 when prescribed Pls and 35 (25%) of 142 with concomitant PI-sparing HAART (chi(2) test; P =.0025). There were no statistically significant differences in the response rates, relapse-free survival, or disease-free survival between patients receiving Pls and those not receiving Pls. PI-based HAART appears to significantly potentiate the myelotoxicity of CDE chemotherapy. This potentiation may be a consequence of microsomal enzyme inhibition reducing the metabolism of cytotoxics in this regimen. (C) 2004 by The American Society of Hematology.