The case for an HIV cure and how to get there

In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products

The KiVa antibullying program in primary schools in Chile, with and without the digital game component: study protocol for a randomized controlled trial.

BACKGROUND: Bullying is a major problem worldwide and Chile is no exception. Bullying is defined as a systematic aggressive behavior against a victim who cannot defend him or herself. Victims suffer social isolation and psychological maladjustment, while bullies have a higher risk for conduct problems and substance use disorders. These problems appear to last over time. The KiVa antibullying program has been evaluated in Finland and other European countries, showing preventive effects on victimization and self-reported bullying. The aims of this study are (1) to develop a culturally appropriate version of the KiVa material and (2) to test the effectiveness of the KiVa program, with and without the online game, on reducing experiences of victimization and bullying behavior among vulnerable primary schools in Santiago (Chile), using a cluster randomized controlled trial (RCT) design with three arms: (1) full KiVa program group, (2) partial KiVa (without online game) program group and (3) control group. METHODS AND DESIGN: This is a three-arm, single-blind, cluster randomized controlled trial (RCT) with a target enrolment of 1495 4th and 5th graders attending 13 vulnerable schools per arm. Students in the full and partial KiVa groups will receive universal actions: ten 2-h lessons delivered by trained teachers during 1 year; they will be exposed to posters encouraging them to support victims and behave constructively when witnessing bullying; and a person designated by the school authorities will be present in all school breaks and lunchtimes using a visible KiVa vest to remind everybody that they are in a KiVa school. KiVa schools also will have indicated actions, which consist of a set of discussion groups with the victims and with the bullies, with proper follow-up. Only full KiVa schools will also receive an online game which has the aim to raise awareness of the role of the group in bullying, increase empathy and promote strategies to support victimized peers. Self-reported victimization, bullying others and peer-reported bullying actions, psychological and academic functioning, and sense of school membership will be measured at baseline and 12 months after randomization. DISCUSSION: This is the first cluster RCT of the KiVa antibullying program in Latin America. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02898324 . Registered on 8 September 2016

Mental Health and School Functioning for Girls in the Child Welfare System : the Mediating Role of Future Orientation and School Engagement

This study investigated the association between mental health problems and academic and behavioral school functioning for adolescent girls in the child welfare system and determined whether school engagement and future orientation meditated the relationship. Participants were 231 girls aged between 12 and 19 who had been involved with the child welfare system. Results indicated that 39% of girls reported depressive symptoms in the clinical range and 54% reported posttraumatic symptoms in the clinical range. The most common school functioning problems reported were failing a class (41%) and physical fights with other students (35%). Participants reported a mean number of 1.7 school functioning problems. Higher levels of depression and PTSD were significantly associated with more school functioning problems. School engagement fully mediated the relationship between depression and school functioning and between PTSD and school functioning, both models controlling for age, race, and placement stability. Future orientation was not significantly associated with school functioning problems at the bivariate level. Findings suggest that school engagement is a potentially modifiable target for interventions aiming to ameliorate the negative influence of mental health problems on school functioning for adolescent girls with histories of abuse or neglect

HIV-1 Pre-Integration Complexes Selectively Target Decondensed Chromatin in the Nuclear Periphery

Integration of the double-stranded DNA copy of the HIV-1 genome into host chromosomal DNA is a requirement for efficient viral replication. Integration preferentially occurs within active transcription units, however chromosomal site specificity does not correlate with any strong primary sequence. To investigate whether the nuclear architecture may affect viral integration we have developed an experimental system where HIV-1 viral particles can be visualized within the nuclear compartment. Fluorescently labeled HIV-1 virions were engineered by fusing integrase, the viral protein that catalyzes the integration reaction, to fluorescent proteins. Viral tests demonstrate that the infectivity of fluorescent virions, including the integration step, is not altered as compared to wild-type virus. 3-D confocal microscopy allowed a detailed analysis of the spatial and temporal distribution of the pre-integration complexes (PICs) within the nucleus at different moments following infection; the fluorescently labeled PICs preferentially distribute in decondensed areas of the chromatin with a striking positioning in the nuclear periphery, while heterochromatin regions are largely disfavored. These observations provide a first indication of how the nuclear architecture may initially orient the selection of retroviral integration sites

Inclusion of mental health in global economic development.

The APEC Mental Health Roadmap has a vision to strengthen mental health and reduce the economic impact of mental illness in the Asia Pacific. To facilitate its implementation, the APEC Digital Hub will heighten exchange and dissemination of best practices in Asia Pacific mental health partnerships, and increase multi-sectoral recognition to invest in mental health to support economic growth

An exploratory algorithm to identify intra-host recombinant viral sequences.

Since recombination leads to the generation of mosaic genomes that violate the assumption of traditional phylogenetic methods that sequence evolution can be accurately described by a single tree, results and conclusions based on phylogenetic analysis of data sets including recombinant sequences can be severely misleading. Many methods are able to adequately detect recombination between diverse sequences, for example between different HIV-1 subtypes. More problematic is the identification of recombinants among closely related sequences such as a viral population within a host. We describe a simple algorithmic procedure that enables detection of intra-host recombinants based on split-decomposition networks and a robust statistical test for recombination. By applying this algorithm to several published HIV-1 data sets we conclude that intra-host recombination was significantly underestimated in previous studies and that up to one-third of the env sequences longitudinally sampled from a given subject can be of recombinant origin. The results show that our procedure can be a valuable exploratory tool for detection of recombinant sequences before phylogenetic analysis, and also suggest that HIV-1 recombination in vivo is far more frequent and significant than previously thought

Phylodynamics of HIV-1 in lymphoid and non-lymphoid tissues reveals a central role for the thymus in emergence of CXCR4-using quasispecies

BACKGROUND: During HIV-1 infection coreceptor switch from CCR5- (R5)- to CXCR4 (X4)-using viruses is associated with disease progression. X4 strains of HIV-1 are highly cytopathic to immature thymocytes. Virtually no studies have evaluated the HIV-1 quasispecies present in vivo within thymic and lymphoid tissues or the evolutionary relationship between R5 and X4 viruses in tissues and peripheral blood. METHODOLOGY/PRINCIPAL FINDINGS: High-resolution phylodynamic analysis was applied to virus envelope quasispecies in longitudinal peripheral blood mononuclear cells (PBMCs) and lymphoid and non-lymphoid tissues collected post mortem from therapy naïve children with AIDS. There were three major findings. First, continued evolution of R5 viruses in PBMCs, spleen and lymph nodes involved multiple bottlenecks, independent of coreceptor switch, resulting in fitter quasispecies driven by positive selection. Second, evolution of X4 strains appeared to be a sequential process requiring the initial fixation of positively selected mutations in V1-V2 and C2 domains of R5 variants before the emergence of high charge V3 X4 variants. Third, R5 viruses persisted after the emergence of CXCR4-using strains, which were found predominantly but not exclusively in the thymus. CONCLUSIONS/SIGNIFICANCE: Our data indicate that the evolution of X4 strains is a multi-step, temporally structured process and that the thymus may play an important role in the evolution/amplification of coreceptor variants. Development of new therapeutic protocols targeting virus in the thymus could be important to control HIV-1 infection prior to advanced disease