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

      • Pulmonary Disease (continued)

        • Fungal Infections of the Lung²

          • There are, other than PCP (Pneumocystis jirovecci), additional fungal infections in the lung are observed in AIDS patients.²  

            • For example, some patients exhibited pulmonary cryptococcal infection.

              • Cryptococcosis is a frequently observed opportunistic infection in AIDS patients.¹³ 

                • However, the infection can also be observed in immunosuppressed individuals.¹³  

                  • Most cases are caused by encapsulated yeast.

                  • Cryptococcus neoformans is the primary causative agent of pulmonary crpytococcal infection, although Cryptococcus gattii also causes some cases.

                    • Cryptococcocisis (Cryptococcus neoformans) of lung in an AIDS Patient¹⁴

                      CDC/ Ewing, Jr. EP (Public Domain-USGOV-HHS-CDC) "Cryptococcosis of lung in patient with AIDS. "Mucicarine stain "Histopathology of lung shows widened alveolar septum contain a few inflammatory cells and numerous yeats of Crytococcus neoformans. "The inner layer of the yeast capsule stains red." (1984)"

                       

                      Cryptococcus gattii

                      Lindsberg J Hagen F Laurens A Stenderup J Boekhout T Crytococcus gatti Risk for Tourists Visiting Vancourver Island, Candaa A) "Chest radiograph and B) "Computed tomography scan of the patient showing 3 nodular Crytococcus gattii infiltrates near pleura"

                    • The most frequent presentation is severe meningioencephalitis.¹³  

                      • Cryptococcal Menningitis¹⁶

                        Attribution:  Meintjes G Update on cryptococcal disease in patients with HIV https://www.youtube.com/watch?v=si_IJiJ65Co (6/2014) HIV/AIDS YouTube Channel:  https://www.cdc.gov/hiv/basics/whatishiv.html

                    • Pulmonary cryptococcosis is likely underdiagnosed in HIV-seropositive patients.¹³  

                      • Furthermore, absent appropriate treatment, severe disseminated disease may ensue.

                        • Although radiological presentations appear varied and nonspecific, depending on the underlying immune status of the individual, diagnosis may be made based on other approaches.

                        • Typically, diagnosis centers on isolation in a pulmonary specimen of Cryptococcus directly from or detection of cryptococcal antigen.¹³  

                        • This finding along with other clinical radiological histopathological findings allow for diagnosis.

              • These patients present with the following symptoms:

                • Fever

                • Cough

                • Hemoptysis

                • Dyspnea.

              • In chest x-ray in over 90% of patients, a focal or diffuse interstitial infiltrate may be documented.

                • The presentation may also include:

                  • Lobular disease

                  • Cavitary disease

                  • Pleural effusions and

                  • Hilar or mediastinal adenopathy.²  

                •  

                  Chest X-ray:  Pulmonary Cryptococcal Infection¹¹

                  Cryptcoccosis, Mycology Online, Pulonmary Cryptocoocal infection, right upper lobe The University of Adelaide http://www.mycology.adelaide.edu.au/Mycoses/Opportunistic/Cryptococcosis/

          • A mold, Coccidioides immitis, found in the Southwest of the United States may induce pulmonary reactivation syndrome in HIV patients.²  

            • These patients may exhibit CD4+ T cell counts <250/μl.

              • Clinical presentations here include:

                • Fever

                • Weight loss

                • Extensive and

                • Diffuse reticulonodular infiltrates (on chest x-ray) and

                • Cough.²  

          • Primary lung infection is also noted with histoplasmosis, typically in disseminated disease, probably due to reactivation.²  

            • Respiratory symptoms tend to be limited, as cough and dyspnea occur in only between 10%-30% of individuals.

            • However, chest x-ray exhibits pathology and about 50% of individuals with diffuse interstitial infiltrate or diffuse small module represent primary presentations here.²

              • Chest X-ray:  Acute histoplasmosis¹²

                CDC/ Renz M "This chest film shows diffuse pulmonary infiltration due to acute histoplasmosis caused by H.. capsulatum. 1963 http://commons.wikimedia.org/wiki/File:Chest_X-ray_acute_pulmonary_histoplasmosis_PHIL_3954.jpg

          • Idiopathic interstitial pneumonia has been described in HIV patients.²  

            • Idiopathic interstitial pneumonia has been mainly of two types:

              • Lymphoid interstitial pneumonia (LIP) and nonspecific interstitial pneumonia (NIP).

                • Although common in children, LIP is noted in about 1% of adult patients not undergoing treatment for HIV.²