Recurring Candida albicans esophagitis in a HIV-infected patient undergoing long-Term antiretroviral therapy, and with absent-negligible immunodeficiency

605 BJID 2007; 11 (December) Recurring Candida albicans Esophagitis in a HIV-Infected Patient Undergoing Long-Term Antiretroviral Therapy, and with Absent-Negligible Immunodeficiency Roberto Manfredi, Sergio Sabbatani and Leonardo Calza Department of Clinical and Experimental Medicine, Division of Infectious Diseases, “Alma Mater Studiorum” University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy A patient with HIV infection developed the first episode of AIDS-defining opportunism (severe Candida albicans μL. After treatment with a highly active esophagitis) with an underlying CD4+ lymphocyte count of 1,025 cells/μ antiretroviral therapy (HAART), taken with insufficient compliance and leaving a residual viral load, our patient suffered from two relapses of esophageal candidiasis, which occurred three months and seven years later, when his μL, respectively, and a viral load slightly above 104 copies/mL was still CD4+ lymphocyte count was 930 and 439 cells/μ present. Also in the HAART era, Candida esophagitis remains one of the most common AIDS-defining diseases, but μL remains a rare exception, as well as the two a presentation with a concurrent CD4+ count above 1,000 cells/μ μL, and a residual HIV isolated, subsequent relapses, occurred with a CD4+ count ranging from 439 to 930 cells/μ viremia due to insufficient adherence to the prescribed HAART regimens. Our case report represents the opportunity to revisit the epidemiology and, especially, the pathogenesis of this opportunistic fungal complication in HIVinfected patients and in other subjects at risk, on the ground of an extensive literature review, and to explore possible alternative supporting factors other than the crude absolute CD4+ lymphocyte count, with emphasis on the possible role of a persisting HIV viremia, and other potential contributing factors. Clinicians engaged with immunocompromised patients and subjects with HIV disease, should be aware that a Candida esophagitis may occur and relapse also when the cell-mediated immunity, as measured by a simple CD4+ cell count, do not show relevant abnormalities. Key-Words: Esophageal candidiasis, HIV infection, CD4+ lymphocyte count, HIV viral load, recurring opportunistic disease, antiretroviral therapy, negligible or absent immunodeficiency. In the era of highly active antiretroviral therapy (HAART) a dramatic drop of immunodeficiency-related opportunism occurred (especially for disorders associated with a CD4+ lymphocyte count below 50-100 cells/μL, like cryptosporidiosis, cytomegalovirosis, atypical mycobacteriosis, isosporiasis, neurotoxoplasmosis, and cryptococcosis) [1-5], compared with the years preceding the introduction of potent antiretroviral combinations (before mid1996) [6-8]. However, in the HAART era the distribution of the main AIDS-defining diseases remained somewhat unchanged in their respective proportion [1-4, 9]. Also recent experiences proved that opportunistic infections are still the major causes of morbidity and mortality in the HAART era [1,3,4,10-12] and the same epidemiological pattern has been very recently confirmed among HIV-infected children [13]. As a consequence, esophageal candidiasis and Pneumocystis carinii pneumonia remained the most frequent AIDS-defining disorders, a decade after the introduction of HAART (1996-2006). In fact, the profile of AIDS notifications in Italy updated on December 31, 2005, reported 56,016 cumulative cases of AIDS, with only 1,577 new cases registered in the last year, Received on 20 August 2007; revised 15 October 2007. Address for correspondence: Dr. Roberto Manfredi. Associate Professor of Infectious Diseases, University of Bologna. Infectious Diseases, S. Orsola Hospital. Via Massarenti 11 - I-40138 Bologna, Italy. Telephone: +39-051-6363355. Telefax: +39-051-343500. E-mail: . The Brazilian Journal of Infectious Diseases 2007;11(6):605-609. © 2007 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved. 2005 [10]. According to these data, esophageal and pulmonary candidiasis and pneumocystosis remain the leading causes of full-blown AIDS, accounting for nearly 40% of overall cases, although a slight decrease of visceral candidiasis was observed in newly diagnosed AIDS patients (both adults and children), who were already taking HAART (from 25.3% of all AIDSrelated disorders observed in the years preceding 1995, down to 18.7% in the years 2004-2005) [10]. This last issue could reflect a more efficient immune response to fungal pathogens in patients recovering immune defence when using HAART, but could indirectly confirm the direct antifungal activity of protease inhibitors, already demonstrated in elegant ex vivo studies [14], and apparently confirmed by preliminary epidemiological and clinical observations [15]. However, among HAART-treated novel AIDS patients, visceral candidiasis still ranks first among AIDS-defining diseases (23.7% of cases) [10]. When assessed according to HIV plasma viral load and CD4+ lymphocyte count, the frequency of esophageal candidiasis was surprisingly greater among patients with an undetectable or a very low HIV viremia (below 500 copies/mL), but a CD4+ count above 200 cells/μL at diagnosis (17.6%), compared with those with <200 cells/μL (16.3%), while among viremic patients (viral load >500 copies/mL), a CD4+ count <200 cells/μL prompted a visceral candidiasis in more subjects than in those with a CD4+ lymphocyte count above 200 cells/μL (26.3% versus 23.9%) [10]. An atypical case report of Candida albicans esophagitis prompting a diagnosis of AIDS in presence of a CD4+ lymphocyte count exceeding 1,000 cells/μL, with two subsequent relapses occurring three months and seven year www.bjid.com.br 606 HIV-Related Esophageal Candidiasis Without Immunodeficiency later, when a HAART therapy was conducted with incomplete patient’s adherence, although ensuring a CD4+ count of 930 and 439 cells/μL respectively, while HIV viremia remained slightly over 104 copies/mL, is described and discussed in its epidemiological, clinical, and especially pathogenic implications, on the basis of an extensive and updated literature review. Case Report A 32-year-old homosexual man followed for 11 years for a HIV/HCV co-infection started seven years ago his first antiretroviral therapy with a didanosine-stavudine-indinavir combination (since October 1999); dysphagia and epigastralgia appeared and progressively worsened, and a mild, associated oropharyngeal candidiasis became apparent. Upon hospitalization, his CD4+ count was 1,025 cells/μL (CD4+ percentage 44%, leading to a CD4+/CD8+ rate >1), while 43,800 copies/mL of HIV RNA were detected. An esophagogastroduodenoscopy showed an extensive esophageal candidiasis, associated with a mild hiatal hernia. The histopathologic examination of biopsy specimens showed a chronic and abundant inflammatory infiltrate involving the lamina propria, mostly represented by mononuclear cells and macro (...truncated)