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Background: Most studies on hepatitis C virus (HCV)/HIV-coinfection do not account for the order and duration of these two infections. We aimed to assess the effect of incident HCVinfection, and its timing relative to HIVseroconversion (HIVsc) in HIV-positiveMSM on their subsequent CD4(+) T-cell count and HIV RNA viral load trajectories. Methods: WeincludedMSMwithwell estimated dates ofHIVsc from 17 cohortswithin the CASCADE Collaboration. HCV-coinfected MSM were matched to as many HIV monoinfected MSM as possible by HIV-infection duration and combination antiretroviral therapy (cART) use. We used multilevel random-effects models stratified by cART use to assess differences inCD4(+) cell count andHIVRNAviral loadtrajectoriesbyHCV-coinfection status. Findings: Wematched 214 (ART-naive) and 147 (on cART) HCV-coinfectedMSMto 5384 and 3954, respectively, matched controls. The timing of HCV seroconversion (HCVsc) relative to HIVsc had no demonstrable effect on HIV RNA viral load or CD4(+) cell count trajectories. In the first 2-3 years following HCVsc CD4(+) cell counts were lower among HCV-coinfected MSM, but became comparable with HIV monoinfected MSM thereafter. In ART-naive MSM, during the first 2 years after HCVsc, HIV RNA viral load levels were lower or comparable with HIV monoinfected, tending to be higher thereafter. In MSM on cART, HCV had no significant effect on having a detectable HIV RNA viral load. Interpretation: Irrespective of the duration of HIV infection when HCV is acquired, CD4(+) cell counts were temporarily lower following HCVsc, even when on cART. The clinical implications of our findings remain to be further elucidated. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of rapid between- and within-host evolution may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by effectively aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to preprocess reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We use shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read data produced with the Illumina platform, for 65 existing publicly available samples and 50 new samples. We show the systematic superiority of mapping to shiver ’s constructed reference over mapping the same reads to the standard reference HXB2: an average of 29 bases per sample are called differently, of which 98.5% are supported by higher coverage. We also provide a practical guide to working with imperfect contigs.

Studies have shown the beneficial effect of normo- and hyper insulinemia on growth rate of GHD children due to craniopharyngioma (BUCHER et al.). Furthermore others showed that insulinotropic drugs improve growth parameters in experimental and clinical situations. To test whether increased insulin secretion or decreased degradation is responsible for improvement of insulinemic status c-peptide (c-p.), insulin (IRI) and glucose responses to 1.75 g/kg b.w. glucose p.o. as well as insulin binding of erythrocytes were measured simultaneously. After informed consent 1O (GHD) children were tested during GH thera py (phase 1) and after more than 6 weeks (phase 2) withdrawal. Glycemic response was normal in both situations, max.IRI and c-p . were reduced as compared to age-matched normal values in both phases. IRI levels were significantly higher in phase 1 than 2, but c-p. showed only a slight insignificant increase in the older age group. Insulin binding (7.5%+-0.8 vs.5.5 +- 0.6 S.D.) and affinity were reduced in phase 2. Comparable results of binding studies were obtained after 7 days of GH-withdrawal. Our results showed down-regulated receptors in phase 1 as evidence of permanently increased insulin levels. We conclude decreased hepatic degradation under GH.