Toxicity studies for the use of prodrug of voriconazole in rats.

It has been reported that voriconazole is used to treat infections caused by invasive aspergillosis, fluconazole-resistant Candida, Actinoplanes and Fusarium. This study was performed to investigate the safety of prodrug of voriconazole (POV) and explore the distribution and metabolism of POV in vivo. The POV for injection was formulated into POV injection. In this study, POV injection was given intravenously at the doses of 0, 30, 60, and 120 mg/kg/d to SD rats for 4 weeks consecutively. Toxicokinetic study was also performed to explore its distribution and metabolism. POV injection was found to be safe and well tolerated. Some statistically significant differences in relative liver weight were observed and several cases of hepatocyte hypertrophy occurred after the 4-week POV injection treatment. Liver-related toxic response could be reversed after recovery period. The results of toxicokinetics showed that POV can rapidly converts to voriconazole in SD rats after administration. The exposure of voriconazole in each group was significantly different between male and female rats. The results showed that the target organ for the toxic effect of POV is liver and the no-toxic-reaction-dose for long-term administration of POV injection was 60 mg/kg/d.

Expansion of HIV care and treatment in Yunnan Province, China: treatment outcomes with scale up of combination antiretroviral therapy.

Effective health care models to scale up combination antiretroviral therapy (ART) are needed in rural southwestern China. We aimed to evaluate the ART treatment outcomes and their associations with patients' demographic characteristics and pre-treatment clinical features in a scaled-up provincial ART program serving eight heavily HIV-affected prefectures in Yunnan Province. We abstracted information from a computerized database for adults initiating ART between July 2007 and September 2008. Survival functions of mortality and treatment failure were calculated by age group, gender, transmission mode, and baseline CD4 count. Multivariable Cox regression analyses were conducted to find independent associations of various demographic and baseline clinical features with outcome variables. Of the 1967 patients in the mortality analysis, there were 110 deaths, of which 16 were coded as accidents or suicides. Adjusted hazard ratios (AHR) associated with mortality were greater for patients with baseline CD4 counts <100 cells/µl vs. patients with CD4 counts ≥200 cells/µl, for male vs. female, for single vs. married, and for those acquired HIV through injection drug use (IDU) vs. other modes of transmission. Successful treatment was 81.3% at six months after treatment started. Immunologic treatment failure was associated with baseline CD4 counts but not with demographic characteristics. Overall loss to follow-up rate was 2.1%. Collaboration between clinics and community networks are distinctive features of Yunnan's model for scaling up ART across a diverse, poor, and rural population. This study finds that the strategy can succeed even if 40% of the patients have a history of IDU.