Medical Pharmacology Chapter 36:  Antiviral Drugs

• Antiviral Drugs

  • Anti-viral drugs with activity against HIV (Human Immunodeficiency Virus)

    • HIV-1 Pathophysiology/Pathogenesis:  HIV Disease Presentations

      Hepatobiliary Dysfunction in HIV (continued)

      • HIV  and Hepatitis C Co-Infection⁹

        • Hepatitis C virus infection is also frequently found in individuals infected with HIV. Individuals infected by HIV as a result of parenteral exposure (e.g. IV drug users or transfusion recipients) exhibit a high likelihood of hepatitis C (HCV) viral infection.⁹ 

          • The likelihood range of this co-infection is from 60%-95% worldwide.

        • Many patients with HIV + HCV coinfection exhibit elevation in serum ALT (alanine aminotransferase) and AST (aspartate aminotransferase) levels.⁹ 

          • Although such elevations may be asymptomatic, chronic HCV infection is associated with hepatic fibrosis or cirrhosis and later by hepatocellular carcinoma or death.

          • Symptoms of end-stage liver disease may include:

            • Portal hypertension

            • Ascites

            • Esophageal varices

            • Splenomegaly

          • Diminished liver synthetic function is evidenced by:

            • Hypoalbuminemia

            • Coagulopathy

            • Thrombocytopenia.

          • Furthermore, hepatic encephalopathy may occur.

        • There are manifestations of hepatitis C infection outside of the liver.

          • Extrahepatic hepatitis C-induced pathologies include

            • Membranous glomerulonephritis

            • Porphyria cutanea tarda

            • Cryoglobulinemia (+/-vasculitis)

        • The presence of HIV infection is associated with increased hepatitis C viral replication as well as by increased hepatic fibrosis progression.⁹ 

          • These effects may be traced to HIV-related immunosuppressive effects.

          • For patient populations receiving cART (HAART) highly active antiretroviral regimens, hepatitis C viral infection is especially prominent as a cause of morbidity and mortality.

            • Because of this observation, individuals found to be HIV positive should be screened for hepatitis C infection through detection of anti-HCV antibodies.

              • In those patients with advanced immunodeficiency due to HIV, reflected in CD4⁺ T cell counts <100/mm³ or in patients with acute HCV infection, nonreactivity for the HCV antibody represents a challenge.

                • In these circumstances blood hepatitis C viral RNA should be directly assessed in those patients suspected of being infected by hepatitis C but who exhibit negative anti-HCV results.

                  • Elevated liver enzyme levels with negative anti-HCV results might suggest the need for direct assessment of HCV RNA.

                  • Those patients positive for the HCV antibody should be further evaluated to confirm active hepatitis C viral replication (testing for HCV RNA, e.g.).

              • To minimize adverse effects of coinfection, efforts to prevent or limit liver damage, HCV transmission, determination of possible chronic liver disease presence and evaluation for anti-hepatitis C virus treatment should be undertaken.

                • Analysis of hepatic disease severity may involve radiographic imaging in addition to measurement of blood serum markers such as AST-to-platelet ratios.⁹

        • Patients with both HIV and acute/chronic HCV infection may benefit from HCV treatment and each case deserves evaluation of therapy benefits versus risks.

          • Some anti-HCV drugs, because of effects on the cytochrome P450 drug metabolizing system may require combination with only selected antiretroviral drugs.⁹

    •  

      Updated Fact Sheet for HIV and Hepatitis C Click Here (8/2021)

      HIV and Viral Hepatitis Center for Disease Control Fact Sheet¹¹

       

       

       

References

Flexner C Antiretroviral Agents and Treatment of HIV Infection, Chapter 59  in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition (Brunton LL Chabner BA Knollmann BC, eds; Brunton LL, ed; Blumenthal DK  Murri N Hilal-Dandan R, assoc eds, Knollmann BC, consulting ed, on-line edition) The McGraw-Hill Companies, 2011. Fauci AS Lane HC Chapter 189, Human Immunodeficiency Virus Disease:  AIDS and Related Disorders, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Longo DL Fauci AS  188, The Human Retroviruses, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Woster PM Chapter 43:  Antiviral Agents and Protease Inhibitors in Foye's Principles of Medicinal Chemistry 6e, Lemke, TL Williams DA, eds; Roche VG Zito SW, asst eds) Wolters Kluwer|Lippincott Williams & Wilkins 1214, 2008. Knox TA Wanke C Gastrointestinal Manifestations of HIV and AIDS  Chapter 397, pp 2196-2199 Goldman's Cecil Medicine 24e (Goldman L and Schafer AI, eds) Elsevier/Saunders, 2012. Public Domain:  Digestive system diagram. http://commons.wikimedia.org/wiki/File:Digestive_system_showing_bile_duct.png Emannuelm Opened gall bladder containing numerous gallstones. http://en.wikipedia.org/wiki/Gallstone; http://commons.wikimedia.org/wiki/File:Gallstones.jpg . Heilman J "A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis. http://commons.wikimedia.org/wiki/File:Gallstones.PNG Haines C Sulkowski MS Gastrointestinal, Hepatobiliary and Pancreatic Manifestations of Human Immunodeficiency Virus Infection.  Chapter 126, 1567-1573 in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8e, Bennett, JE Dolin R Blaser MJ, eds, 2015). Weyer D Hepatitis A,B and C:  Diagnosis and Treatment in HIV-Infected Persons. https://www.youtube.com/watch?v=yANIfjow8SE  (July, 2010) CDC fact sheet:  HIV and Viral Hepatitis http://www.cdc.gov/hepatitis/Populations/PDFs/HIVandHep-FactSheet.pdf ; check here for updated information:  http://www.cdc.gov/hepatitis/Populations/hiv.htm

 

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