Metabolic and Cardiovascular Complications in HIV/HCV-Co-infected Patients.

PURPOSE OF REVIEW: Fifteen to thirty percent of HIV-infected persons in North America and Europe are co-infected with chronic hepatitis C (HCV). The latter is associated with a significant number of extra-hepatic metabolic complications that could compound HIV-associated increased cardiovascular risk. This article reviews the basic science and epidemiologic and clinical evidence for increased cardio-metabolic risk among HIV/HCV-co-infected patients and discusses potential underlying mechanisms. We will finally review the impact of control of HCV viremia on the cardio-metabolic morbidity and mortality of HIV/HCV-co-infected patients. RECENT FINDINGS: HCV infection is associated with a number of immune-related complications such as cryoglobulinemia but also metabolic complications including dyslipidemias, hepatic steatosis, insulin resistance, diabetes, and chronic kidney disease. The incidence of these complications is higher among HIV-co-infected patients and might contribute to increased mortality. The potential mechanisms of increased cardiovascular risk among HIV/HCV-co-infected subjects include endothelial dysfunction, chronic inflammation and immune activation, the cardio-metabolic effects of HCV-induced hepatic steatosis and fibrosis or insulin resistance, and chronic kidney disease. However, epidemiologic studies show discordant findings as to whether HCV co-infection further increases the risk of atherosclerotic cardiovascular diseases (acute myocardial infarctions and strokes) among HIV-infected patients. Nonetheless, successful treatment of HCV is associated with significant improvements in cardio-metabolic risk factors including diabetes mellitus. HCV co-infection is associated with a higher incidence of metabolic complications-and likely increased risk of cardiovascular events-that might contribute to increased mortality in HIV. These appear to improve with successful HCV therapy.

Colchicine toxicity precipitated by interaction with sunitinib.

WHAT IS KNOWN AND OBJECTIVE: Colchicine is an anti-inflammatory agent used primarily in treatment of gout and familial Mediterranean fever. Toxicity is uncommon, and depends on dose, hepatic or renal impairment, co-administration with P-glycoprotein or CYP3A4 inhibitors and route of administration. In patients taking p-glycoprotein inhibitors, maximum recommended dose is 0·3 mg per day. In renal or hepatic impairment, recommendation is to avoid concomitant administration of p-glycoprotein inhibitors and colchicine. CASE SUMMARY: We present an 82 year old patient, with a history of gout, chronic kidney disease and recurrent renal cell carcinoma who was admitted with features of colchicine toxicity after taking a cumulative dose of 41·4 mg over ten days, and taking sunitinib 50 mg daily from day seven of his high dose colchicine regimen. Symptoms started after commencing his cycle of sunitinib, which he had taken in 14 day cycles for many years. He developed severe diarrhea, normal anion gap metabolic acidosis, fever, pneumonia, white cell abnormalities including 30% bands and toxic granulation with Dohle bodies. Red cell abnormalities included anemia, burr cells and acanthocytosis. He also developed acute cardiovascular collapse with hypotension and acute systolic heart failure. Cardiac catheterization showed previously known coronary artery disease, with no significant progression to explain degree of cardiovascular collapse. WHAT IS NEW AND CONCLUSION: P-glycoprotein inhibition by sunitinib has been demonstrated. Interaction with colchicine metabolism precipitated colchicine toxicity in this case. Knowledge of p-glycoprotein and its role in drug interactions and potential drug toxicity may not be widespread among clinicians. We report the first case of colchicine toxicity precipitated by interaction with a tyrosine kinase inhibitor.