Children's spontaneous correction of false beliefs in a conversation partner.

Preschool children were tested for their ability to vary the verbal information they offered regarding an object's location depending on whether the person searching for that object was likely to infer or misinfer its location. Older children (mean age: 5 years 3 months) offered information in a selective fashion: If the location of the hidden object could be readily inferred by their conversation partner, they indicated its location only when explicitly asked but if its location was likely to be misinferred, they often indicated that location prior to being explicitly asked. The response pattern of younger children (mean age: 3 years 6 months) was less conclusive. A relatively large number of younger children took matters "into their own hands" and immediately grasped for the concealed object, irrespective of whether its location could be readily inferred. However, the reactions of the remaining 3-year-olds suggest that even at this age children may be sensitive to the likely beliefs of their conversation partner. © 1999 The International Society for the Study of Behavioural Development

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Back to base pairs

Red blood cell (RBC) alloimmunization is a serious complication of blood transfusions, challenging selection of compatible units for future transfusions. Genetic characteristics may be associated with the risk of RBC alloimmunization and may therefore serve to identify high-risk patients. The aim of this systematic review was to summarize the available evidence on genetic risk factors for RBC alloimmunization. Electronic databases were searched up to April 2020 for studies (Search terms included transfusion, alloimmunization and genetic). A total of 2581 alloimmunized cases and 26,558 controls were derived from 24 studies. The alleles that were most frequently studied and that demonstrated significant associations in a meta-analysis with alloimmunization to the Duffya antigen were HLA-DRB1*04 (Odds Ratio 7.80 (95%CI 4.57–13.33)), HLA-DRB1*15 (OR 3.76 (95%CI 2.14–6.59)), and HLA-DRB1*03 (OR 0.12 (95%CI 0.05–0.29)). Furthermore, significant associations with anti-K formation was found for the alleles HLA-DRB1*10 (OR 2.64 (95%CI 1.41–4.95)), HLA*DRB1*11 (OR 2.11, (95%CI 1.34–3.32)), and HLA-DRB1*13 (OR 1.71 (95%CI 1.26–2.33)). Overall, the available evidence was of moderate to low quality, hampering interpretation of reported results. There is an urgent need for high quality evidence on genetic risk factors for RBC alloimmunization.</p

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

BACKGROUND: In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children &lt;18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P &lt; .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

International audienceIn human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART

High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe