Hepatitis C treatment outcome in former or current intravenous drug users coinfected with HIV, with or without directly observed therapy.

BACKGROUND: Intravenous drug users (IDUs) with hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfection are recognised as a high-risk, vulnerable group. METHODS: Between February 2015 and April 2018, a single-centre, non-interventional cohort study was conducted in an outpatient setting, to evaluate the sustained virologic response (SVR12) and assess treatment uptake models. The study included 385 former or recent IDUs divided into two groups: A-without use of opioid substitution treatment (OST) and B-patients taking opioid substitution; patients in group B received OST and self-administered therapy (B1) or OST and therapy under DOT (B2). Patients were characterised by demographic and clinical features and compared for treatment response. Correlations between SVR12 and independent variables were determined by logistic regression. RESULTS: Patients were mostly males (88.3%) with a mean age of 46 ± 5 years and HCV genotype 1a (63.7%). Approximately 28% were treatment-experienced and 84.9% received sofosbuvir/ledipasvir. The mean CD4+T count was 649 cells/mm3, and most individuals were on antiretroviral therapy with undetectable viral loads (97.4%). SVR12 was achieved in 94.8%, and only eight patients relapsed. No significant differences were found in treatment effect between individuals taking opioid substitutes under different treatment models. Correlations were found between HCV viral response and both HIV suppression and albumin levels. CONCLUSIONS: IDU with HCV/HIV coinfection, including individuals on self-administration of HCV therapy and opioid substitution treatments or in DOT programmes, are no longer considered a difficult-to-treat group, as they achieve high rates of SVR12.

Optimisation of reactive dye degradation by laccase using Box-Behnken design.

A three-level Box-Behnken factorial design with three factors and the Response Surface Methodology were used to optimise the colour removal of the reactive textile dye, Colour Index (C.I.) reactive red 180, by commercial laccase. A mathematical model was developed to study the effect of temperature, pH, enzyme concentration and their interactions on the decolourisation. Enzyme concentration and pH as well as their interaction were the principal factors that affected the decolourisation. The dye degradation was independent of temperature. The model estimated that the highest decolourisation (> 92%) was obtained for 27 degrees C, pH 7.5 and 85 U l(-1). This predicted value was experimentally validated, obtaining dye colour removal (540 nm) of 93 +/- 1.5%.

Optimization and modeling of laccase production by Trametes versicolor in a bioreactor using statistical experimental design.

Experimental design and response surface methodologies were applied to optimize laccase production by Trametes versicolor in a bioreactor. The effects of three factors, initial glucose concentration (0 and 9 g/L), agitation (100 and 180 rpm), and pH (3.0 and 5.0), were evaluated to identify the significant effects and its interactions in the laccase production. The pH of the medium was found to be the most important factor, followed by initial glucose concentration and the interaction of both factors. Agitation did not seem to play an important role in laccase production, nor did the interaction agitation x medium pH and agitation x initial glucose concentration. Response surface analysis showed that an initial glucose concentration of 11 g/L and pH controlled at 5.2 were the optimal conditions for laccase production by T. versicolor. Under these conditions, the predicted value for laccase activity was >10,000 U/L, which is in good agreement with the laccase activity obtained experimentally (11,403 U/L). In addition, a mathematical model for the bioprocess was developed. It is shown that it provides a good description of the experimental profile observed, and that it is capable of predicting biomass growth based on secondary process variables.

Decolorization of dyes from textile wastewater by Trametes versicolor.

The white rot fungus Trametes versicolor was applied to the decolourisation of three synthetic textile dyes in the presence and absence of glucose. Different initial dye concentrations were tested and approximately 97% decolourisation was achieved. It was found that fungal metabolism induced by the glucose as well as the pH play an important role in the decolourisation process. This treatment was also applied to a real wastewater from a textile industry-dyeing sector leading to 92% decolourisation.

Comparison of the biodistribution of free or liposome-entrapped Crotalus durissus terrificus (South American rattlesnake) venom in mice.

The local absorption rate, clearance and tissue distribution of Crotalus durissus terrificus venom, (Cdt) were examined using a two-antibody sandwich ELISA assay. We compared the biodistribution of both free or encapsulated Cdt in mice. Following subcutaneous injection of 10 microg/mouse of free Cdt (0.8 LD50), venom was detected in serum after 15 min, showed its highest level at 30 min (45+/-5 ng/ml) and was cleared from the circulation after 6 h. After 2 h of inoculation, venom was detected in the kidney (57+/-9 ng/g of tissue), spleen (18+/-4 ng/g of tissue) and brain (14+/-6 ng/g of tissue). For both subcutaneous or intravenous injection of free Cdt, venom was firstly detected in the kidney. No Cdt appeared either in the kidney, spleen, brain, or other tissues after subcutaneous inoculation of encapsulated venom even though a higher dose was used, 25 microg/mouse (2 LD50). Venom remained at the site of injection for a period of 1 week. Following intravenous injection of encapsulated venom (5 microg/mouse, 2 LD50), venom was detected in liver and spleen tissues. The biodistribution of encapsulated venom is discussed in relation to the effects of reduction of toxicity and increase of adjuvanticity.

[Kaposi sarcoma associated with HIV infection]. / Sarcoma de Kaposi associado a infecção pelo VIH.

Kaposi's sarcoma is the most common neoplasm in AIDS patients. In a 12-year period, 45 (8%) cases were diagnosed in 552 patients with AIDS. Epidemiological and clinical aspects are reviewed. The disease occurred predominantly in males and homosexuals. In 30 (67%) patients it was the first manifestation of AIDS. Skin and/or oral disease was the most frequent manifestation observed in our patients; 13 (29%) had visceral involvement. Previous or concommitant opportunistic diseases, systemic illness and severe immunosuppression were present in the majority of the patients. Opportunistic infections were the cause of death in 30 patients; in five others, Kaposi's sarcoma was responsible for death. Advances in antiretroviral therapy were of benefit for patients submitted to chemotherapy and may contribute to a reduction in morbidity with this neoplasm.

Use of liposomes for protective immunisation against Crotalus durissus (tropical rattlesnake) venom.

Crotalus durissus venom has been described as a weak antigen when injected in combination with Freund's complete adjuvant during the course of traditional methods of equine immunisation. Antibody production is slow and unpredictable, with a wide variation in individual responses. In this experimental study, C. durissus venom was incorporated into stabilised sphingomyelin-cholesterol liposomes both in the presence and absence of lipopolysaccharide immunostimulant and injected by both i.v. and s.c. routes into mice and rabbits. A rapid, sustained and protective immune response was obtained following a single injection of these preparations in mice. Antibody levels were estimated using enzyme-linked immunosorbent assay (ELISA), and the protective effect was evaluated by subsequent challenge with a subcutaneous minimum lethal dose of the venom. Results indicated that the immune response was significantly potentiated by the presence of immunostimulant in the venom liposomes. The use of C. durissus venom liposomes should be a useful tool for the immunisation of animals both in experimental and commercial procedures.