title: Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.
abstract: Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91-55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL. Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.
authors.affiliation: From Division of Infectious Diseases (TM, RNG), Department of Internal Medicine, and Department of Public Health (TNC), University of Kentucky, Lexington, Kentucky; Division of Infectious Diseases (AMA), Department of Internal Medicine, Emory University, Atlanta, Georgia; Division of Infectious Diseases (AS), Department of Internal Medicine, University of Southern California, Los Angeles, California; Division of Infectious Diseases (AF), Department of Internal Medicine, University Medical Center of Southern Nevada, Las Vegas, Nevada; Department of Pulmonary and Critical Care Medicine, Thoracic Transplantation (CH), Indiana University Health, Indianapolis, Indiana; Division of Infectious Disease (JWB), Department of Internal Medicine, University of Alabama, Birmingham, Alabama; Departmentof Epidemiology (MJ), College of Public Health, University of Louisville, Louisville, Kentucky; Division of Infectious Disease (DMB), Department of Internal Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri; and MiraVista Diagnostics (MR, LJW), Indianapolis, Indiana.
authors.forename: Thein
authors.initials: T
authors.lastname: Myint
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez
authors.forename: Alireza
authors.initials: A
authors.lastname: Farabi
authors.forename: Chadi
authors.initials: C
authors.lastname: Hage
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
authors.forename: Malhar
authors.initials: M
authors.lastname: Jhaveri
authors.forename: Richard N
authors.initials: RN
authors.lastname: Greenberg
authors.forename: David M
authors.initials: DM
authors.lastname: Bamberger
authors.forename: Mark
authors.initials: M
authors.lastname: Rodgers
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Crawford
authors.forename: L Joseph
authors.initials: LJ
authors.lastname: Wheat
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D006660:Histoplasmosis / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents