Similarly, pharmacodynamic interactions, in particular overlapping toxicities between ARVs and systemic anticancer therapy, suggest

that some drug combinations should be avoided in patients with HIV-associated cancers. Much of the guidance on the use of individual ARV agents with systemic anticancer therapy comes from reviews of potential drug interactions rather than from clinical studies [65-67]. The pharmacokinetic interactions between ARVs and systemic anticancer therapy are not confined to cytotoxic chemotherapy agents and extensive interactions with newer targeted therapies such as imatinib, erlotinib, sorafenib, bortezomib and temsirolimus have been described [67]. We suggest avoiding ritonavir-boosted ART in HIV-positive patients who are to receive cytotoxic this website chemotherapy agents that are metabolized Natural Product Library nmr by the CYP450 enzyme system (2C). In general, clinically important pharmacokinetic drug interactions with systemic anticancer therapies are most common with PI/r-based ART and most clinicians avoid these combinations where possible. For example, in a cohort study, the rates of severe infections and severe neutropenia following chemotherapy for AIDS-related NHL were significantly higher among patients receiving concomitant PI (mainly ritonavir boosted) than in those on NNRTI-based ART regimens, although there was no difference in survival between the groups [68]. Furthermore,

case reports of clinically significant life-threatening interactions between ritonavir-boosted-based ART and docetaxel [69], irinotecan [70] and vinblastine [71] have been published. We recommend against the use of ATV in HIV-positive patients who are to receive irinotecan (1C). The camptothecin cytotoxic agent irinotecan is extensively metabolized by uridine diphosphoglucuronosyl transferase 1A1 isoenzymes that are inhibited by ATV [72]. In patients with Gilbert’s syndrome, who have a congenital Dimethyl sulfoxide deficiency of uridine diphosphoglucuronosyl transferase 1A1, irinotecan administration has led to life-threatening toxicity [73].

We suggest avoiding ARV agents in HIV-positive patients who are to receive cytotoxic chemotherapy agents that have overlapping toxicities (2C). Both ARV agents and systemic anticancer therapies have substantial toxicity and where these overlap it is likely that the risk of toxicity is greater. For example, ZDV commonly causes myelosuppression and anaemia [74], which are also frequent side effects of cytotoxic chemotherapy and so these should not be co-prescribed where possible. Similarly, dideoxynucleosides cause peripheral neuropathy [75], a common toxicity of taxanes and vinca alkaloids, so co-prescribing should be avoided. Both ZDV and dideoxynucleosides are no longer recommended for initiation of ART but some treatment-experienced patients may still be receiving these drugs and alternatives should be considered.