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 Oropharynx and Gastrointestinal System:

      • Frequently observed presentations of HIV infection include both oropharyngeal gastrointestinal diseases.² 

        • These presentations are most typically observed as a result of secondary infections as a result of HIV-induced immunodeficiency.

        • Oral lesions, frequently seen in untreated HIV infection include thrush, leukoplakia and aphthous ulcers.² 

          •  

            Thrush:  Oropharyngeal candidiasis⁵

            Schubert M Spach DH Case 1 Oral Candidiasis: HIV Web Study, University of Washington, (Figure 1)  Washington University, 2011. Oral candidiasis is a CDC category B diagnosis, utilizing the 1993 CDC classification system.6  There are four distinct manifestations or candidiasis including: Pseudomembranous candidiasis (thrush) Atrophic (erythematous) candidiasis Angular chilitis and rarely Hyperplastic candidiasis. The image in the figure above is an example of pseudomembranous candidiasis.5

          • Thrush as a result of Candida infection is  suggestive of relatively advanced immunologic compromise.

          • Oral hairy leukoplakia, probably due to Epstein-Barr virus (EBV), is also indicative of relatively advanced immunologic compromise.

            • These diseases are most likely seen in patients with CD4+ T cell counts of <300/µL.² 

            • The white appearance in oral hairy leukoplakia is due to hyperkeratosis and epithelial hyperplasia.⁹  

              • Following initial resolution of a primary Epstein-Barr viral infection, viral persistence remains due to latent B lymphocyte infection.¹⁰ 

              • Epstein-Barr virus causes oropharyngeal lytic infections which are not controlled in immunocompromised individuals and manifest as oral hairy leukoplakia.

                • Oral hairy leukoplakia may be noted in individuals receiving transplants and are accordingly on immunosuppressive drugs; however, typically the immunocompromise is secondary to immunological suppression due to HIV/AIDS.⁹ 

            • "Epstein-Barr Virus (EBV)/ Oral hairy Leukoplakia"⁷

              Credit:  Pediatric AIDS Pictoral Atlas, Baylor International pediatric AIDS Initiative Description:  "Oral hairy leukoplakia in an HIV-infected girl. "Hairy leukoplakia is typified by the presence of white or gray lesions along the lateral tongue. Lesions often have vertical corrugations and are not removable with a tongue blade. This is in Epstein-Barr virus associated lesion."7 VA Image Library:  HIV/AIDS http://www.hiv.va.gov/provider/image-library/epstein-barr.asp?post=1&slide=129

            •  

              "Epstein-Barr Virus (EBV)/ Oral hairy Leukoplakia"⁸

              Greenspan D, University of California San Francisco "Oral hairy leukoplakia appearing as corrugations on the lateral margin of the tongue."8 VA Image Library:  HIV/AIDS http://www.hiv.va.gov/provider/image-library/epstein-barr.asp?post=1&slide=31

           

          • Aphthous ulcers sometimes also referred to as aphthous stomatitis may be seen in patients with HIV infection.² 

            • One prominent site for aphthous ulcers is the posterior oropharynx.²  

              • However, other locations such as tongue and lips are common.¹² 

            • HIV patients not receiving contemporary anti-retroviral agents are at a higher risk.¹²  

            • Furthermore, these lesions may be painful, interfering with swallowing.^2,11

              •  Symptoms may exhibit "prodromal" sensations including burning or itching prior to lesion appearance.¹¹ 

                • Pain associated with these ulcers is worst just following initial ulcer formation.¹¹

            •  

              Aphthous Stomatitis (Aphthous Ulcers)¹²

              As shown above, these lesions present as oval or round ulcerations with a raised red border.12  Lesion depth is variable. Lesion centers are covered with a pseudomembrane which may be gray, white or yellow. In HIV-infected individuals these lesions are known to also occur in the esophagus and anogenital region.12,13

           

          • Esophagitis

            • Esophagitis presents as retrosternal pain along with difficulty in swallowing (odynophagia).² 

              • Definitive diagnosis usually depends on upper endoscopy.

              • Several causes are responsible for esophagitis including:

                • Candida

                • Cytomegaloviral infection (CMV)

                • Herpes simplex viral infection (HSV).

              • Gastrointestinal manifestations of HIV:  Esophagitis¹⁶

                Volberding PA Gastrointestinal manifestations of HIV: Esophagitis  University of California San Francisco.16 U.S.  Department of Veterans Affairs Image Library http://www.hiv.va.gov/provider/image-library/gastrointestinal.asp?post=1&slide=187

              • If a single large ulcers found, the cause is probably CMV.

                • By contrast, multiple small ulcers suggest herpes simplex virus as causative.²  

              The most common esophageal infection in HIV-infected patients is due to Candida (Candidal esophagitis).¹⁴ 

              • Gastrointestinal manifestations of HIV: 

                 Candida esophagitis¹⁵

                Volberding PA Gastrointestinal manifestations of HIV:  Candida Esophagitis  University of California San Francisco.15 U.S.  Department of Veterans Affairs Image Library http://www.hiv.va.gov/provider/image-library/gastrointestinal.asp?post=1&slide=188

              • A combination of dysphasia along with oral thrush predicts at a level of 90% esophageal candidiasis.¹⁴  

                • At CD4⁺ T cell counts <50/µL CMV as well as idiopathic esophageal ulcerations may be more likely found.

                  • In this setting, significant pain on swallowing is typically the first symptom.

                  • Endoscopy often reveals large ulcerations with elevated margins; CMV inclusions are noted in biopsy analysis.

                • Esophagitis due to herpes simplex virus infections (CMV) are much less likely to occur and are associated with relatively shallow esophageal ulcerations. Idiopathic disease is diagnosed by the absence of viral evidence upon biopsy.¹⁴