Intracranial hemorrhage and liver-associated deaths associated with tipranavir/ritonavir: review of cases from the FDA's Adverse Event Reporting System.
ABSTRACT Tipranavir (TPV), a protease inhibitor, has box warnings for intracranial hemorrhage (ICH) and hepatotoxicity (including hepatic failure and death). A box warning is a labeling statement about serious adverse events leading to significant injury and/or death. A box warning is the most serious warning placed in the labeling of a prescription medication. As a result of the respective morbidity and mortality associated with ICH and hepatic failure, the Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) was searched for reports of these adverse events in HIV-infected patients receiving a tipranavir/ritonavir (TPV/r)-based regimen. This search comprised part of the FDA's safety analysis for traditional approval. From July 2006 to March 2007, 10 cases of ICH were identified in AERS. From June 2005 to March 2007, 12 cases of liver-associated deaths were identified. One patient experienced liver failure and fatal ICH. Most patients with these events had additional risk factors. Among patients with liver-associated deaths, 3 had HIV-RNA less than 400 copies per milliliter at the time of hepatic failure. Among 10 patients who discontinued TPV/r when hepatic failure developed, median number of days post-TPV/r to death was 23 (range, 2-69 days). Review of AERS did not identify new safety concerns regarding ICH. Among most patients with liver-associated deaths, death appears to occur soon after hepatic failure develops. If considering TPV/r, careful assessment of risk/benefit is suggested for patients at risk for ICH and hepatic failure.
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ABSTRACT: Audit standards: 1. All new HIV-positive patients should be screened for HBV and HCV markers. 2. All HBV non-immune patients should be vaccinated. 3. All HIV-positive patients should have their HBV and HCV status measured before commencement of antiretroviral therapy. 4. All HBV-and HCV-infected patients should be vaccinated against hepatitis A if non-immune. 5. All HCV-positive patients non-immune to HBV should be vaccinated. 6. All HBV-and HCV-infected patients should have documented evidence in their case notes of a discussion on alcohol avoidance and how to reduce the risks of transmission. 7. Case notes of new HBV-positive patients should contain evidence of an attempt to contact household and sexual contacts and offer vaccination if non-immune. 8. Case notes of new HCV-positive patients should contain evidence of an attempt to notify parenteral and sexual contacts and offer them a test. 9. All patients who are HBsAg-positive or HCV-positive should have a clear antiviral treatment plan written in their notes at least once a year. 10. All HCV-RNA-positive patients should have an HCV viral load and genotype performed. 11. All HBV-positive patients should have their 'e' status checked, an HBV DNA viral load and an anti-HDV antibody test. 12. All patients with chronic HBV or HCV should be offered an assessment of liver fibrosis by either liver biopsy, hepatic elastography or other validated non-invasive fibrosis test unless they have a specified contra-indication. 13. All HBV-positive patients with an HBV DNA >2000IU/mL and evidence of liver damage should be offered treatment. 14. All HCV-RNA-positive patients should be offered treatment unless there is a specific contra-indication. 15. All patients with cirrhosis should be jointly treated by a hepatologist and have regular assessments for hepatocellular carcinoma according to risk.
Article: Antiretroviral Therapy Current Drugs[Show abstract] [Hide abstract]
ABSTRACT: The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date.Infectious Disease Clinics of North America 09/2014; 28(3):371-402. DOI:10.1016/j.idc.2014.06.001 · 2.31 Impact Factor
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ABSTRACT: Rates of admission to the intensive care unit (ICU) for persons infected with human immunodeficiency virus (HIV) remain relatively unchanged in the modern era despite advances in antiretroviral therapy (ART) and improvements in ICU survival. Critical care may be required for patients with HIV because of severe opportunistic infections or malignancy, antiretroviral drug toxicity, or critical illness seemingly unrelated to HIV, and each of these scenarios may present different management challenges. In this article, the epidemiology of HIV-related ICU admission is reviewed and key management issues are discussed.Critical care clinics 07/2013; 29(3):603-20. DOI:10.1016/j.ccc.2013.03.010 · 2.50 Impact Factor