Immigrant HIV-infected adults in industrialized countries show a poorer clinical and virologic outcome compared with native patients. We aimed to investigate potential differences in clinical, ...immunological, and virologic outcome in Dutch HIV-infected children born in the Netherlands (NL) versus born in Sub-Saharan Africa (SSA) in a national cohort analysis.
We included all HIV-infected children registered between 1996 and 2013. Descriptive statistics, mixed-effects models, and Cox proportional hazard models were used to investigate differences between groups.
In total, 319 HIV-infected children were registered. The majority of these children were born in SSA (n = 148, 47%) or NL (n = 113, 36%) and most were black (n = 158, 61%). Children born in NL were diagnosed at a median age of 1.2 years and initiated combination antiretroviral therapy (cART) at a median age of 2.6 years, compared with 3.7 and 5.3 years, respectively, for children born in SSA (HIV diagnosis: P < 0.001; cART initiation: P < 0.001). Despite a lower initial CD4 T-cell Z-score in children born in SSA, their immunological reconstitution was similar to children from NL. Virologic suppression was achieved in the majority of all cART-treated children (NL: 96%, SSA: 94%). There was no difference in the occurrence or timing of virologic failure.
Most immigrant HIV-infected children living in NL were born in SSA. Children born in SSA were diagnosed and initiated cART at an older age than children born in NL. Despite initial differences in CD4 T-cell counts and HIV viral load, the long-term immunological and virologic response to cART was similar in both groups.
The long-term treatment of human immunodeficiency virus (HIV)-infected children with combination antiretroviral therapy (cART) requires assessment of potential adverse effects, such as osteoporosis. ...Longitudinal data on bone mineral density (BMD) in HIV-infected children showed that cumulative treatment with cART had a positive impact on BMD over time.
Highlights • The incidence of Coxsackievirus (CV)-A6 associated disease is increasing worldwide. • We describe an atypical course of CV-A6 infection in preterm twins. • The infection was mild despite ...the presence of risk factors for severe disease. • The CV-A6-strains are genetically closely related to strains circulating globally.
The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of ...gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.
To improve adherence and virologic suppression, we assessed the feasibility and effectiveness of a once-daily regimen of efavirenz with 3 nucleoside reverse transcriptase inhibitors as first-line or ...second-line highly active antiretroviral therapy in a cohort of HIV-1-infected children.
HIV-1-infected children naive to efavirenz were treated with a combination of efavirenz, abacavir, didanosine, and lamivudine in an observational, prospective, single-center study. Virologic failure-free survival was assessed with Kaplan-Meier analysis. The CD4+ T-cell increase was estimated by using a generalized linear model incorporating repeated measurements.
Thirty-six children received the study medication for a median of 69 weeks. Virologic failure-free survival rates were 76% and 67% after 48 weeks and 96 weeks, respectively. No significant difference was found in efficacy between first-line and second-line highly active antiretroviral therapy. All children receiving highly active antiretroviral therapy showed a sustained CD4+ T-cell increase, irrespective of virologic suppression. Growth rates improved with highly active antiretroviral therapy. Study medication administration was stopped for 14 children, mostly because of nonadherence (4 cases) or virologic rebound (5 cases) and because of adverse events (unrelated death and grade 2 liver toxicity) in 2 cases. Lipid abnormalities and abacavir-related hypersensitivity were not observed.
For the first time, once-daily highly active antiretroviral therapy is demonstrated to be a safe, convenient, and potent antiretroviral regimen for HIV-1-infected children.
To determine the effects of IL-10 on cytokine and granulocyte responses during endotoxemia, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once ...in combination with placebo injection, and once in conjunction with i.v. administered recombinant human IL-10 (rhIL-10) (25 microg/kg). In group 1, rhIL-10 was administered 2 min before endotoxin challenge; in group 2, the intervention was delayed for 1 h after endotoxin administration. rhIL-10 pretreatment reduced the LPS-induced rises in temperature and release of TNF, IL-6, IL-8, and IL-1 receptor antagonist. Endotoxin-induced granulocyte accumulation in lungs, as determined by dynamic granuloscintigrams, was prevented by rhIL-10 pretreatment, whereas granulocyte recruitment in liver and spleen was only modestly reduced. In addition, granulocyte degranulation, as measured by plasma elastase/alpha1-antitrypsin complexes, was blunted significantly by rhIL-10 pretreatment. Post-treatment with rhIL-10 did not influence LPS-induced temperature responses, cytokine release, or granulocyte degranulation. Both rhIL-10 pretreatment and post-treatment reduced LPS-induced cortisol levels. These results indicate that pretreatment with rhIL-10 reduces endotoxin-induced febrile responses, cytokine responses, and granulocyte accumulation in lungs, while in this acute model post-treatment with rhIL-10 exerts limited anti-inflammatory effects.
The results of studies with cultured endothelial cells have shown that most von Willebrand factor (vWF) synthesized is directly secreted (constitutive pathway) and consists of both mature vWF, its ...precursor molecule pro-vWF, and the cleaved vWF prosequence. Only fully processed, functionally mature vWF is stored within the cell, together with the propeptide, and leaves the cell only on stimulation (regulated secretion). Both in resting and stimulated cultured endothelial cells, the stoichiometry of the released propeptide to the released mature vWF is essentially equimolar. In the present study, we have measured the molar ratio of propeptide to mature vWF in vivo, both under resting conditions and conditions that reflect activation of the endothelium. To this end, we devised a method that allows the measurement of the propeptide (vW antigen II) on a quantitative, ie, molar basis, using purified recombinant propeptide as a standard. Our results show that the molar concentration of the propeptide in normal plasma is about one tenth of the concentration of mature vWF (expressed as half-dimer concentration). This ratio is approximately 1:1 in the medium of cultured endothelial cells. On administration in healthy subjects of either 1-deamino-8-D-arginine vasopressin or endotoxin, both agents being known to elicit an intravascular increase of vWF, the molar ratio of propeptide to mature vWF increased fourfold to fivefold. The propeptide concentration returned to baseline values after about 6 to 7 hours of injection of each stimulus, whereas the increase of mature vWF was much more sustained. Because the respective half-lives of mature vWF and its propeptide clearly differ, measurement of the concentration of these proteins could provide a means to assess the extent of activation of the endothelium under physiological and pathophysiological conditions.
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