Late presentation of HIV infection : a consensus definition

OBJECTIVES: Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection. METHODS: Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition of what is meant by a 'late-presenting' patient. RESULTS: Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/\u3bcL or presenting with an AIDS-defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease: persons presenting for care with a CD4 count below 200 cells/\u3bcL or presenting with an AIDS-defining event, regardless of the CD4 cell count. CONCLUSION: The European Late Presenter Consensus working group believe it would be beneficial if all national health agencies, institutions, and researchers were able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infectio

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

<p>Abstract</p> <p>Background</p> <p>Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures.</p> <p>Results</p> <p>Incubation of oxymetholone (<b>1</b>) with <it>Macrophomina phaseolina</it>, <it>Aspergillus niger</it>, <it>Rhizopus stolonifer</it>, and <it>Fusarium lini</it> produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (<b>2</b>), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (<b>3</b>), 17α-methyl-5α-androstan-2α,3β,17β-triol (<b>4</b>), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (<b>5</b>), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (<b>6</b>), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (<b>7</b>). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds <b>2</b>–<b>5</b> were identified as the new metabolites of <b>1</b>. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds <b>1</b>–<b>7</b> were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC₅₀ values between 31.2 to 2.7 μg/mL, while the IC₅₀ values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay.</p> <p>Conclusion</p> <p>Microbial transformation of oxymetholone (<b>1</b>) provides an efficient method for structural transformation of <b>1</b>. The transformed products were obtained as a result of <it>de novo</it> stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.</p