Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy.

Globally, 1·7 million children are living with HIV, of which 90% are in sub-Saharan Africa. The remarkable scale-up of combination antiretroviral therapy has resulted in increasing numbers of children with HIV surviving to adolescence. Unfortunately, in sub-Saharan Africa, HIV diagnosis is often delayed with children starting antiretroviral therapy late in childhood. There have been increasing reports from low-income settings of children with HIV who have multisystem chronic comorbidities despite antiretroviral therapy. Many of these chronic conditions show clinical phenotypes distinct from those in adults with HIV, and result in disability and reduced quality of life. In this Review, we discuss the spectrum and pathogenesis of comorbidities in children with HIV in sub-Saharan Africa. Prompt diagnosis and treatment of perinatally acquired HIV infection is a priority. Additionally, there is a need for increased awareness of the burden of chronic comorbidities. Diagnostic and therapeutic strategies need to be collectively developed if children with HIV are to achieve their full potential

Provision of antiretroviral treatment in conflict settings: the experience of Médecins Sans Frontières

ABSTRACT: INTRODUCTION: Many countries ravaged by conflict have substantial morbidity and mortality attributed to HIV/AIDS yet HIV treatment is uncommonly available. Universal access to HIV care cannot be achieved unless the needs of populations in conflict-affected areas are addressed. METHODS: From 2003 Médecins Sans Frontières introduced HIV care, including antiretroviral therapy, into 24 programmes in conflict or post-conflict settings, mainly in sub-Saharan Africa. HIV care and treatment activities were usually integrated within other medical activities. Project data collected in the Fuchia software system were analysed and outcomes compared with ART-LINC data. Programme reports and other relevant documents and interviews with local and headquarters staff were used to develop lessons learned. RESULTS: In the 22 programmes where ART was initiated, more than 10,500 people were diagnosed with HIV and received medical care, and 4555 commenced antiretroviral therapy, including 348 children. Complete data were available for adults in 20 programmes (n = 4145). At analysis, 2645 (64%) remained on ART, 422 (10%) had died, 466 (11%) lost to follow-up, 417 (10%) transferred to another programme, and 195 (5%) had an unclear outcome. Median 12-month mortality and loss to follow-up were 9% and 11% respectively, and median 6-month CD4 gain was 129 cells/mm 3.Patient outcomes on treatment were comparable to those in stable resource-limited settings, and individuals and communities obtained significant benefits from access to HIV treatment. Programme disruption through instability was uncommon with only one program experiencing interruption to services, and programs were adapted to allow for disruption and population movements. Integration of HIV activities strengthened other health activities contributing to health benefits for all victims of conflict and increasing the potential sustainability for implemented activities. CONCLUSIONS: With commitment, simplified treatment and monitoring, and adaptations for potential instability, HIV treatment can be feasibly and effectively provided in conflict or post-conflict settings

Tuberculosis : opportunities and challenges for the 90-90-90 targets in HIV-infected children

CITATION: Rabie, H., Frigati, L., Hesseling, A. C. & Garcia-Prats, A. J. 2015. Tuberculosis : opportunities and challenges for the 90-90-90 targets in HIV-infected children. Journal of the International AIDS Society, 18(Suppl 6):20236, doi:10.7448/IAS.18.7.20236.The original publication is available at http://www.jiasociety.orgIntroduction: In 2014 the Joint United Nations Programme on HIV/AIDS defined the ambitious 90 90 90 targets for 2020, in which 90% of people living with HIV must be diagnosed, 90% of those diagnosed should be on sustained therapy and 90% of those on therapy should have an undetectable viral load. Children are considered to be a key focus population for these targets. This review will highlight key components of the epidemiology, prevention and treatment of tuberculosis (TB) in HIV-infected children in the era of increasing access to antiretroviral therapy (ART) and their relation to the 90 90 90 targets. Discussion: The majority of HIV-infected children live in countries with a high burden of TB. In settings with a high burden of both diseases such as in sub-Saharan Africa, up to 57% of children diagnosed with and treated for TB are HIV-infected. TB results in substantial morbidity and mortality in HIV-infected children, so preventing TB and optimizing its treatment in HIV-infected children will be important to ensuring good long-term outcomes. Prevention of TB can be achieved by increasing access to ART to both children and adults, and appropriate provision of isoniazid preventative therapy. Co-treatment of HIV and TB is complicated by drug-drug interactions particularly due to the use of rifampicin; these may compromise virologic outcomes if appropriate corrective actions are not taken. There remain substantial operational challenges, and improved integration of paediatric TB and HIV services, including with antenatal and routine under-five care, is an important priority. Conclusions: TB may be an important barrier to achievement of the 90 90 90 targets, but specific attention to TB care in HIV-infected children may provide important opportunities to enhance the care of both TB and HIV in children.http://www.jiasociety.org/index.php/jias/article/view/20236?search=rabiePublisher's versio

Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome : a case report

CITATION: Glanzmann, B., et al. 2020. Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome : a case report. BMC Medical Genetics, 21:124, doi:10.1186/s12881-020-01054-6.The original publication is available at https://bmcmedgenet.biomedcentral.comBackground: The X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in the WAS gene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes. Case presentation: Here, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identified c. 397 G > A as a novel hemizygous missense mutation located in exon 4 of WAS. Conclusion: With definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-020-01054-6Publisher's versio

Advancing the prevention and treatment of HIV in children: priorities for research and development

Safe and effective paediatric formulations of the most promising antiretroviral drugs are crucial to advance the treatment and prevention of HIV in neonates, infants, children, and adolescents. The WHO Paediatric Drug Optimization for HIV (PADO-HIV) group brings together stakeholders and experts every 2-3 years to identify priority products and define research gaps in the development of new HIV drugs and formulations for children in low-income and middle-income countries. PADO-HIV 5 met from Sept 27 to Oct 15, 2021. The group evaluated HIV agents from known and novel drug classes, oral and parenteral long-acting formulations, and developments in broadly neutralising antibodies, and included focused sessions on neonates and new delivery technologies. A list of medium-term and long-term priorities was generated, and research questions were defined. This forward-looking analysis is intended to provide guidance to funders, drug developers, and researchers, and to accelerate access for children to the best HIV drugs and formulations