Itraconazole Prophylaxis for Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection: Randomized, Placebo‐Controlled, Double‐Blind Study

Abstract

In a prospective, randomized, double-blind trial, 149 patients with advanced human immunodeficiency virus (HIV) infection were randomized to receive itraconazole capsules (200 mg daily) and 146 to receive a matched placebo. Both groups were monitored for evidence of fungal infections. Baseline characteristics of the two groups were similar. Failure of prophylaxis occurred in 29 (19%) of the itraconazole recipients and 42 (29%) of the placebo recipients (P = .004; log-rank test). There were 6 invasive fungal infections in the itraconazole group (4, histoplasmosis; 1, cryptococcosis; 1, aspergillosis) and 19 in the placebo group (10, histoplasmosis; 8, cryptococcosis; 1, aspergillosis) (P = .0007; log-rank test). Itraconazole significantly delayed time to onset of histoplasmosis (P = .03; log-rank test) and cryptococcosis (P = .0005; log-rank test). Prophylaxis failure due to recurrent or refractory mucosal candidiasis occurred with similar frequency in the two groups (itraconazole, 15%; placebo, 16%). A survival benefit was not demonstrated. Itraconazole generally was well tolerated. Primary prophylaxis with itraconazole capsules prevents histoplasmosis and cryptococcosis in patients with HIV infection.

Does Long-Term Itraconazole Prophylaxis Result in In Vitro Azole Resistance in Mucosal Candida albicans Isolates from Persons with Advanced Human Immunodeficiency Virus Infection?

“…Approximately one-third of subjects who received itraconazole, however, developed at least one episode of mucosal candidiasis. Prophylaxis did not reduce the incidence of recurrent candidiasis requiring treatment with systemically absorbed antifungal agents (2).…”

“…In this report, we assessed the effect of long-term antifungal treatment on the susceptibility of oral C. albicans isolates to both itraconazole and fluconazole in patients randomized to either an itraconazole or a placebo group for the prevention of systemic mycoses (2). This study is unique in that it examined the effect of prophylaxis on susceptibility of C. albicans isolates in the largest cohort of HIV-infected subjects treated with long-term itraconazole and allowed for a comparison to a placebo group.…”

“…strains obtained from patients with AIDS who participated in a trial of antifungal prophylaxis (2). This multicenter, randomized, double-blind study enrolled subjects living in areas of endemicity for histoplasmosis with CD4 cell counts of Յ150/mm 3 .…”

Histoplasmosis: a Clinical and Laboratory Update

“…For those who do not achieve immune reconstitution, maintenance therapy with 200 mg itraconazole daily should continue for life. It has also been established that prophylaxis with 200 mg itraconazole daily is effective at preventing histoplasmosis in patients with AIDS who have CD4 counts below 150 cells/l (86). However, with the use of effective antiretroviral therapy, rates of histoplasmosis have fallen in the AIDS population, and prophylaxis is no longer recommended.…”

Prevención de las infecciones oportunistas en pacientes adultos y adolescentes infectados por el VIH. Recomendaciones de GESIDA/Plan Nacional sobre el Sida. Año 2003

“…En zonas endémicas, la histoplasmosis se puede prevenir evitando actividades de riesgo como las visitas a cuevas, la exposición al polvo ambiental, el talado de árboles, la limpieza de gallineros y el derribo o desescombro de edificios (CIII). La profilaxis primaria sólo está indicada en pacientes con una cifra de linfocitos T CD4+ menor de 100/l y con alto riesgo por exposición ocupacional o que vivan en zonas hiperendémicas (CI) 85 . En España podría plantearse en inmigrantes infectados por VIH originarios de países endémicos.…”