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

      HIV Effects on the Gastrointestinal System (continued):

      • Protozoal Infections:

        • Opportunistic protozoal infections of the G.I. tract can cause diarrhea in HIV-infected individuals.² 

          • The most common protozoa in this regard include cryptosporidia, microsporidia and Isospora belli.² 

            • Cryptosporidial infection exhibits a broad range of clinical presentations, from intermittent diarrhea in those HIV-infected individuals in the earlier stages to life-threatening diarrhea in HIV infected individuals who are severely immunocompromised.

            • For those HIV-infected patients who are untreated and who exhibit CD4⁺ T cell counts of <300/µL, cryptosporidosis occurs with an incidence of about 1%/year.

              • Most of the time, 75% of cases, diarrhea is associated with crampy abdominal pain; furthermore, about 25% of individuals also experience nausea and vomiting.

            • Cryptosporidia may also, in the HIV-infected individual, cause biliary tract disease which can lead to cholecystitis presenting with or without cholangitis and pancreatitis resulting from papillary stenosis.

            • Cryptosporidia diagnosis may be established either by small intestine biopsy or stool examination.²

              •  

                Cryptosporidosis⁶

                Nephron:  Cryptosporidosis Cryptosporidia sites are depicted within the "squares" in the image http://commons.wikimedia.org/wiki/File:Cryptosporidiosis_-_very_high_mag_-_cropped.jpg

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                "Life cycle of Cryptosporidium spp., the Causative Agents of Cryptosporidosis"⁷

                CDC/ da Silva AJ Moser M Life Cycle of Cryptosporidium spp. http://commons.wikimedia.org/wiki/File:Cryptosporidiosis_01.png

             

            • Cryptosporidosis prevalence depends on geographic region.⁸ 

              • Regions with highest rates appear in developing countries.

              • Cryptosporidosis cases most frequently occur in young children, an observation suggesting that host immune response status is an important factor in susceptibility.

              • Individuals infected with HIV and exhibiting pronounced immunodeficiency may experience cryptosporidosis not only involving the gastrointestinal tract but also the hepatobiliary and respiratory tracts.⁸  

                • Effective management of cryptosporidosis in this patient subset depends on administration of antiviral drugs.⁸  

                  • In HIV patients with CD4⁺ T cell counts >1000/µL, cryptosporidosis may be seen in about 25% of patients.

                    • This percentage rises to about 50% in patients with CD4⁺ T cell counts <100/µL.⁸ 

              • A clinical study published in 1999 evaluated intestinal protozoa in HIV-infected individuals residing in Apulia, South Italy.⁹ 

                • The study involved 154 HIV-infected patients with or without diarrhea, residing in Apulia, South Italy evaluated between December 1993 and February 1998.

                • For most patients CD4+ T cell count was <200/µL.

                • HIV patients were not receiving HIV antiviral medications. ⁹ 

                • The overall prevalence of intestinal protozoa was about 28%, comprised of 28/65 patients presenting with diarrhea and 15/89 non-diarrheic individuals.

                  • For the group of 65 patients with diarrhea, 14 presented with Cryptosporidium parvum, 7 with Blastocystis hominis, 6 with microsporidia, 4 with Giardia lamblia and one with Isospora belli.

                    • Three patients were infected both with Cryptosporidium parvum and microsporidia.

                    • Most cryptosporidosis cases were first identified during periods of heaviest rainfall, suggesting that drinking water contamination could be a possible source of human infection in this region.⁹