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Objectives: The aim of the study was to investigate the dynamics of cytomegalovirus (CMV) replication and CMV‐specific immune response recovery after antiretroviral treatment (ART) initiation in patients with advanced HIV infection. Methods: A prospective observational study of patients with HIV infection and CD4 counts of < 100 cells/µL was carried out (September 2015 to July 2018). HIV viral load (VL), CD4 count and CMV VL were determined by quantitative polymerase chain reaction (PCR) at baseline and at 4, 12, 24 and 48 weeks, and CMV‐specific immune response was determined by QuantiFERON‐CMV assay at baseline and 48 weeks. All patients were started on ART but only those with CMV end‐organ disease (EOD) received anti‐CMV treatment. Results: Fifty‐three patients with a median age of 43.6 [interquartile range (IQR) 36.7–52.4] years were included in the study. At baseline, the median CD4 count was 30 cells/µL (IQR 20–60 cells/µL) and the median HIV VL was 462 000 HIV‐1 RNA copies/mL (IQR 186 000–1 300 000 copies/mL). At baseline, 32% patients had detectable CMV viraemia but none had detectable CMV viraemia at 48 weeks. Only one of 53 (1.9%) patients developed EOD during follow‐up. Seven (13.2%) patients were lost to follow‐up and six (11.3%) died; none of the deaths was related to CMV. Similar percentages of patients had a CMV‐specific immune response at baseline (71.7%) and at 48 weeks (70.0%). The magnitude of this response tended to increase over time [median 1.63 (IQR 0.15–5.77) IU/mL at baseline vs. median 2.5 (IQR 0.1–8.325) IU/mL at 48 weeks; P = 0.11]. We did not find any risk factors associated with 48‐week mortality. Conclusions: Although the prevalence of CMV viraemia in patients with advanced HIV infection remains high, achieving a good immunological recovery through ART is enough to suppress CMV viraemia, without an increased risk of CMV EOD. The prevalence of a CMV‐specific immune response was high and endured over time. [ABSTRACT FROM AUTHOR]

Abstract Exogenous administration of insulin-like growth factor I (IGF-I) restores motor function in rats with neurotoxin-induced cerebellar deafferentation. We first determined that endogenous IGFs are directly involved in the recovery process because infusion of an IGF-I receptor antagonist into the lateral ventricle blocks gradual recovery of limb coordination that spontaneously occurs after partial deafferentation of the olivo-cerebellar circuitry. We then analysed mechanisms whereby exogenous IGF-I restores motor function in rats with complete damage of the olivo-cerebellar pathway. Treatment with IGF-I normalized several markers of cell function in the cerebellum, including calbindin, glutamate receptor 1 (GluR1), γ-aminobutyric acid (GABA) and glutamate, which are all depressed after 3-acetylpyridine (3AP)-induced deafferentation. IGF-I also promoted functional reinnervation of the cerebellar cortex by inferior olive (IO) axons. In the IO, increased expression of bax in neurons and bcl-X in astrocytes after 3AP was significantly reduced by IGF-I treatment. On the contrary, IGF-I prevented the decrease in poly-sialic-acid neural cell adhesion molecule (PSA-NCAM) and GAP-43 expression induced by 3AP in IO cells. IGF-I also significantly increased the number of neurons expressing bcl-2 in brainstem areas surrounding the IO. Altogether, these results indicate that subcutaneous IGF-I therapy promotes functional recovery of the olivo-cerebellar pathway by acting at two sites within this circuitry: (i) by modulating death- and plasticity-related proteins in IO neurons; and (ii) by impinging on homeostatic mechanisms leading to normalization of cell function in the cerebellum. These results provide insight into the neuroprotective actions of IGF-I and may be of practical consequence in the design of new therapeutic approaches for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]