Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents Disease Specific Recommendations Asperegillosis   Epidemiology     Aspergillosis, most frequently caused by Aspergillus fumigatus but occasionally by other Aspergillus species, was more common before the advent of potent ART among patients with advanced HIV-1 disease .Specific risk factors include neutropenia, low CD4+ T lymphocyte count, use of corticosteroids, exposure to broad spectrum antibacterial therapy, and previous pneumonia or other underlying lung disease. Patients who have had HIV-1--associated aspergillosis diagnosed typically have extremely low CD4+ T lymphocyte counts (i.e., <50 cells/µL), a history of other AIDS-defining opportunistic infections, and are not receiving ART.   Clinical Manifestations Two major syndromes have been described among patients with AIDS: respiratory tract disease (either semi-invasive pseudomembranous tracheitis or invasive pneumonitis) and CNS infection occurring as a febrile diffuse meningoencephalitis syndrome with vascular infarction as a central feature (based on the predilection of Aspergillus organisms to invade blood vessel walls). Semi-invasive pseudomembranous tracheitis is associated with fever, cough, dyspnea, stridor or wheezing caused by airway constriction, culminating in airway obstruction if untreated. Endoscopic examination demonstrates a confluent, exudative pseudomembrane adherent to the tracheal wall. Invasive pneumonitis occurs with fever, cough, dyspnea, chest pain, hemoptysis, and hypoxemia; chest radiograph demonstrates either a diffuse interstitial pneumonitis or a localized wedge-shaped dense infiltrate representing pulmonary infarction, related to the predilection of the organisms for invasion of vascular endothelium. Diagnosis A definitive diagnosis requires the presence of relevant clinical signs and symptoms and the histopathologic demonstration of organisms in biopsy specimens obtained from involved sites or from a site that is expected to be sterile (e.g., liver or brain). A presumptive diagnosis of respiratory tract disease can be made in the absence of a tissue biopsy if Aspergillus spp. are cultured from a respiratory sample, a compatible lesion or syndrome is present, and no alternative causative process is identified. Serologic testing is not helpful. Treatment Recommendations The recommended treatment for invasive aspergillosis is voriconazole. Amphotericin B, either conventional or lipid formulations, in doses equivalent to 1 mg/kg body weight/daily of standard amphotericin B is an alternative regimen (AIII). Voriconazole has not been studied in this patient population. Caspofungin is approved for patients failing to tolerate or improve with standard therapy; however, it has not been studied in this patient population. Monitoring and Adverse Events Patients should be monitored for adverse effects related to amphotericin B. Airway obstruction can result from extensive pseudomembrane formation in those with tracheitis. Pulmonary infarction and progressive interstitial pneumonitis can lead to respiratory failure. Management of Treatment Failure The overall prognosis is poor among patients with advanced immunosuppression and in the absence of effective ART. Treatment failure is generally defined as failure to respond to initial therapy or progression of clinical signs and symptoms despite appropriate therapy. No data are available to guide recommendations for the management of treatment failure. If amphotericin B was used initially, substitution with voriconazole might be considered; the alternative approach would be rational for those who began therapy with voriconazole (BIII). Prevention of Recurrence No data are available to base a recommendation for or against chronic maintenance or suppressive therapy among those who have successfully completed an initial course of treatment (CIII). Special Considerations During Pregnancy As with other invasive fungal infections, aspergillosis should be treated the same in pregnancy as in the nonpregnant adult, with the exception that amphotericin B is the preferred agent in the first trimester because of the potential teratogenic risks for the azoles, if efficacy is expected to be superior or similar to that of the azoles (BIII). x .