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)

      • In addition to hepatitis B and hepatitis C viruses, numerous other infectious agents can contribute to hepatic pathologies such as hepatocellular necrosis or granulomatous inflammation.⁹

        • Hepatocellular Necrosis¹⁶

          Kleiner DE Acute Hepatic necrosis (due to acetominophen) "A few viable hepatocytes are left near the vein, but most are present as hepatocyte ghosts. "Macrophages (arrows) have infiltated into the necrotic zone. "Hepatocytes around the edges of the necrosis show ballooning injury and steatosis*." *steatosis:  fatty degeneration

        •  

          Granulomatous inflammation¹⁷

          Greenson JK Granulomatous inflammation PBC:  primary biliary cirrhosis

        • Hepatocellular pathologies may be caused by:

          • Cytomegalovirus (CMV)

          • Epstein-Barr virus (EBV)

          • Adenovirus

          • Herpes simplex virus (HSV)⁹ 

        • Mycobacterial and fungal organisms may also promote granulomatous inflammations.⁹ 

          • The most common opportunistic hepatic pathogen in the mycobacterial group is Mycobacterium avium complex (MAC).

            • M. avium complex infection may result in disseminated disease.

              • Symptoms associated with disseminated disease may include fever, sweats, weight loss and anemia.

        • Extrapulmonary Mycobacterium tuberculosis (M. tuberculosis) may cause hepatic disease in about 5%-10% of HIV-related cases.⁹ 

          • Mycobacterium tuberculosis¹⁵

            Ewing Jr EP/CDC Mycobacterium tuberculosis,  1994

          • Widespread fungal infections by a number of pathogens may cause hepatic granulomatous reactions.  Such pathogens include:⁹

            • Cryptococcus neoformans (C. neoformans)

              • Cryptococcus neoformans¹⁴

                Beards G Cryptococcus neoformans, an encapsulated years, stained by Gram's method (Demers T, preparation), Feb. 18, 2012 http://en.wikipedia.org/wiki/Cryptococcus_neoformans http://commons.wikimedia.org/wiki/File:Cryptococcus_Gram_film.jpg

            • Histoplasma capsulatum (H. capsulatum)

              •  

                Histoplasma capsulatum¹³ 

                Ajello L/CDC (Centers for Disease Control and Prevention) Histoplasmosis capsulatum "Note the histopathologic changes seen in histoplasmosis due to Histoplasma capsultum using methenamine silver stain. "Note the presence of typical yeast cells, some of which are undergoing replication by 'budding'.  Histoplasmosis can be confined to the lungs, or become systemically disseminated,  thereby, producing a fatal outcome."

            • Coccidioides immitis (pathogenic fungus)

              • Coccidioides immitis¹²

                Hardin/CDC Arthrocondia of Coccidioides immitis, 1965

            • Penicillium marneffei

              • Penicillium marneffei¹¹

                Gathany J (Centers for Disease Control and Prevention, CDC) The surface of a Penicillium marneffei colony http://en.wikipedia.org/wiki/Penicillium_marneffei http://commons.wikimedia.org/wiki/File:Penicillium_marneffei_colony.jpg

            • Candida albicans (C. albicans)

              • Candida albicans¹⁰

                Colm  G Candida albicans http://commons.wikimedia.org/wiki/File:Candida_albicans_2.jpg

                 

        • Pneumocystis jirovecii (P. jirovecii, PCP) is another cause of liver infection and may be more often observed during pentamidinec prophylaxis.⁹ 

        • Bartonella henselae infection may result in peliosis hepatitis.

          • Peliosis hepatitis is more likely associated with profound immunodeficiency.

      • Finally, prior to generalized use of cART (combination anti-retroviral treatment), the most frequently observed hepatic malignancy was Kaposi's sarcoma.⁹