Suchergebnisse

Maraviroc (MVC), the first approved CC‐chemokine receptor 5 (CCR5) antagonist, is used for treating HIV‐1‐infected patients with CCR5 tropism. MVC has been proved safe in all respects and showed beneficial effects on lipid profile of HIV patients with dislipidemia. Adipocyte dysfunction seems to be responsible for many metabolic alterations such as insulin resistance and dislipidemia. Subcutaneous and visceral fat depots are not only physiologically but also metabolically different and metabolic disturbances are more closely associated with visceral than subcutaneous fat accumulation. It has been suggested that antiretrovirals affect both fat depots in a different extent. Thus, whether isolated human adipocytes display regio‐specific sensitivity to the metabolic effects of MVC have been tested in this study. Human subcutaneous and omental preadipocytes were used as the source of human adipocytes. These cells were treated with therapeutic concentrations of MVC (0.5–25 µM) at day 14 post‐differentiation (4 and 24 hours of treatment). Glucose utilization, lactate production and glycerol released into the media were measured using an autoanalyzer. Adiponectin secretion was determined by an ELISA array. A dose‐dependent increase in glucose uptake was observed in subcutaneous adipocytes treated with MVC (+72% of stimulation for MVC 25 µM, p < 0.01). This stimulatory effect was tissue specific, as no effects were observed in omental adipocytes. MVC did not exert any significant effect on adiponectin secretion. No significant effects were observed on lactate production neither in subcutaneous nor omental adipocytes. Interestingly, 4 hours of treatment with MVC induced a significant increase in the amount of glycerol released into the media by subcutaneous adipocytes (p < 0.001), but this effect disappeared with longer exposure of adipocytes to MVC (24 h). No effects were observed on lipolysis in omental adipocytes although a slight tendency to decrease lipolysis was observed (p = 0.08). These data suggest that MVC exerts direct and differential effects on adipocytes depending on their origin. Thus, a stimulation of glucose uptake has been reported in subcutaneous but not in omental adipocytes and a slight decrease of lipolysis was observed in omental adipocytes whereas no effects were observed in subcutaneous adipocytes. These actions could underline the neutral and even beneficial effects demonstrated for MVC in lipid and glucose metabolism of HIV‐infected patients.

There is little evidence assessing compliance with clinical practice guidelines for antiretroviral treatment and its impact on clinical outcomes. The Spanish national guidelines for antiretroviral treatment are published by the Spanish AIDS Study Group (GeSIDA). The aim of this study was to assess compliance with national guidelines for the treatment of naïve patients from a multicentre Spanish cohort (CoRIS). The specific aims were to evaluate the proportion of patients treated according to the guidelines' recommendations, to investigate factors associated with the prescription of a non‐recommended treatment, and to assess the impact of non‐recommended treatments on mortality and on virological and immunological response (defined as undetectable viral load and increase of 100 CD4/ml, respectively, after 1 year). Drug combinations were classified as recommended, alternative, or not recommended, according to the guidelines' "what to start with" recommendations. 6225 naïve patients were included between the years 2004 and 2010. Among 4516 patients who started treatment, 3592 (79.5%), 540 (12%), and 384 (8.5%) started with a recommended, alternative and not‐recommended treatment, respectively. The use of a not‐recommended treatment was significantly associated with CD4 count >500/ml (OR: 2.03, 95% CI: 1.14–3.59), hepatitis B infection (OR: 2.23, 95% CI: 1.50–3.33), treatment in a hospital with <500 beds, and starting treatment in the years 2004 to 2006. There was no significant association of having a not‐recommended treatment with gender, route of transmission, hepatitis C infection, country of origin, education, or viral load. The use of a not‐recommended regimen was significantly associated with mortality (HR: 1.61, 95% CI: 1.03–2.52, p=0.035) and lack of virological response (OR: 0.65, 95% CI: 0.45–0.93, p=0.019), but it was not associated with immunological response (OR: 0.90, 95% CI: 0.75–1.08, p=0.273). In conclusion, compliance with "what to start with" recommendations of Spanish national guidelines was high. The use of not‐recommended regimens was more likely in patients with >500 CD4/ml, hepatitis B infection, and starting treatment in the years 2004–2006 and in small hospitals. Not‐recommended regimens were associated with higher mortality and lack of virological response.