Clinical and microbiological assessment of patients with a long-term diagnosis of human immunodeficiency virus infection and Candida oral colonization.

The objective of this study was to evaluate Candida oral colonization in human immunodeficiency virus (HIV)-infected patients undergoing long-term highly active antiretroviral therapy (ARV). The cross-sectional study included 331 HIV patients, diagnosed from 1983 to 2003. Oral swabs were performed, and Candida species were determined using ID 32C. Isolates were tested for antifungal susceptibility. Clinical and laboratory data were collected to identify the association with Candida colonization. In total, 161 Candida isolates were detected among 147 of the 331 patients (44%), independently of the time when HIV infection was diagnosed. Candida albicans strains represented 137 (85%) of the isolates, and were susceptible to all of the tested antifungal drugs. Among the non-C. albicans strains, six isolates were dose-dependently susceptible to fluconazole, nine to itraconazole, and seven to ketoconazole. The isolation of Candida was significantly higher in patients with virological failure (83/147; p 0.0002) and CD4(+) T-lymphocyte counts <200 cells/mm(3) (30/83; p 0.0003). Recovery of Candida in the oral cavity was independent of protease inhibitor (PI) usage (p 0.60). Colonized patients typically underwent salvage therapy (p 0.003), and had more episodes of opportunistic fungal infections (p 0.046) and malignancies (p 0.004).Oral Candida colonization in patients under ARV therapy was associated with the immunosupressed status of HIV-infected patients, i.e. low number of CD4(+) T-cells per cubic millimetre, failure of ARV therapy (salvage therapy), and higher number of opportunistic infections and malignancies. Despite the fact that PIs have in vitro antifungal activity, the use of this class of antiretroviral agent did not influence the presence of Candida in the oral cavity of AIDS patients.

Comparative studies of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine.

OBJECTIVES: To compare the efficacy and safety of two-times-daily versus three-times-daily indinavir in combination with zidovudine and lamivudine. DESIGN: Two multicenter, open-label, randomized 24-week studies. METHODS: Adults HIV-1 infection, HIV-1 RNA greater than 10000 copies/ml, and no prior lamivudine or protease inhibitor therapy were eligible. In a pilot study (Study A), patients received indinavir at 800 mg every 8 h, 1000 mg every 12 h, or 1200 mg every 12 h. In a subsequent study (Study B), patients received indinavir at 800 mg every 8 h or 1200 mg every 12 h. All subjects received zidovudine (300 mg) and lamivudine (150 mg) every 12 h. An intent-to-treat analysis was used. RESULTS: In Study A, which enrolled 88 patients, neither HIV-1 RNA nor CD4 cell responses differed significantly between treatment groups at 24 weeks when corrected for multiple comparisons. Study B enrolled 433 patients, but was prematurely discontinued when interim analysis suggested greater efficacy of three-times-daily indinavir. Of the first 87 patients reaching week 24, HIV-1 RNA was less than 400 copies/ml in 91% receiving three-times-daily versus 64% receiving two-times-daily indinavir (P < 0.01). CONCLUSION: Three-times-daily indinavir appears more efficacious than two-times-daily dosing when administered with zidovudine and lamivudine. Two-times-daily indinavir dosing should only be considered in situations characterized by favorable pharmacokinetic drug-drug interactions.

Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents.

Fourteen patients with active schistosomiasis mansoni in spite of previous treatment with oxamniquine and/or hycanthone were treated with praziquantel, single oral dose of 45 to 50 mg/kg body-weight. All underwent clinical, laboratory and electrocardiographic examination before and after treatment. Untoward effects (dizziness, drowziness, nausea and abdominal pain) were observed in ten. Laboratory findings disclosed no significant alteration and the electrocardiograms showed no abnormalities. Monthly follow-up examinations of 13 patients for six consecutive months showed parasitological cure in all. Before praziquantel treatment strains of Schistosoma mansoni were isolated from two patients, one treated three times with oxamniquine and the other with hycanthone once and oxamniquine twice. Progenies of these strains were maintained in Biomphalaria glabrata and mice. Groups of these infected mice were then treated with oxamniquine, hycanthone, niridazole and praziquantel and results compared with the BH strain maintained in our laboratory for many years. Schistosomicidal activity was assessed by the localization of worms in the portal vein system and oogram changes. Progenies from the strains isolated in this study were resistant to oxamniquine and hycanthone but sensitive to niridazole and praziquantel. The BH strain was sensitive to all four drugs. The serial runs of S. mansoni strains through intermediate and definitive hosts have not influenced their reactions to these schistosomicides.