Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania

Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART).; GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up.; This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART.; This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org

Protecting children in low-income and middle-income countries from COVID-19

CITATION: Ahmed, S. et al. 2020. Protecting children in low-income and middle-income countries from COVID-19. BMJ Global Health, 5:e002844. doi:10.1136/bmjgh-2020-002844.The original publication is available at https://gh.bmj.comA saving grace of the COVID-19 pandemic in high-income and upper middle-income countries has been the relative sparing of children. As the disease spreads across low-income and middle-income countries (LMICs), long-standing system vulnerabilities may tragically manifest, and we worry that children will be increasingly impacted, both directly and indirectly. Drawing on our shared child pneumonia experience globally, we highlight these potential impacts on children in LMICs and propose actions for a collective response.https://gh.bmj.com/content/5/5/e002844.abstractPublisher's versio

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

INTRODUCTION Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood

Cultural considerations in health care capacity building: A qualitative study in Lesotho

International non-governmental organisations (NGOs) and academic institutions support health care capacity building to strengthen health systems in low and middle-income countries. We conducted a phenomenological study of foreign and Basotho clinicians who participated in clinical continuing professional development (CPD) in Lesotho. Clinicians included physicians, nurses, and a nutritionist. We sought to understand, through the lens of social cognitive theory, how cultural differences between foreign and Basotho clinicians affected bidirectional clinical education led by NGOs and academic institutions. We also assessed how Basotho clinical educators considered culture when leading NGO-sponsored clinical CPD for Basotho clinicians. After analysing 17 interviews with 24 total participants (four foreign educators, 11 Basotho educators, and nine Basotho learners), using an iterative and inductive approach, we identified 17 themes within the cognitive, environmental, and behavioural domains. Key findings highlighted: (1) cultural tensions between foreign and Basotho culture, including bias against traditional culture; (2) power structures which affected the efficacy of in-service training strategies; (3) perceptions among foreign educators that technical assistance was more effective than direct service delivery at promoting education and sustainability. Educators should map out key relationships and engage local and foreign stakeholders in culturally-focused targeted needs assessments to improve curricular design in capacity building

Cultural considerations in health care capacity building: A qualitative study in Lesotho

International non-governmental organisations (NGOs) and academic institutions support health care capacity building to strengthen health systems in low and middle-income countries. We conducted a phenomenological study of foreign and Basotho clinicians who participated in clinical continuing professional development (CPD) in Lesotho. Clinicians included physicians, nurses, and a nutritionist. We sought to understand, through the lens of social cognitive theory, how cultural differences between foreign and Basotho clinicians affected bidirectional clinical education led by NGOs and academic institutions. We also assessed how Basotho clinical educators considered culture when leading NGO-sponsored clinical CPD for Basotho clinicians. After analysing 17 interviews with 24 total participants (four foreign educators, 11 Basotho educators, and nine Basotho learners), using an iterative and inductive approach, we identified 17 themes within the cognitive, environmental, and behavioural domains. Key findings highlighted: (1) cultural tensions between foreign and Basotho culture, including bias against traditional culture; (2) power structures which affected the efficacy of in-service training strategies; (3) perceptions among foreign educators that technical assistance was more effective than direct service delivery at promoting education and sustainability. Educators should map out key relationships and engage local and foreign stakeholders in culturally-focused targeted needs assessments to improve curricular design in capacity building

Feasibility of Implementing an Early Intervention Program in an Urban Low-Income Setting to Improve Neurodevelopmental Outcome in Survivors Following Birth Asphyxia

Birth asphyxia is a leading cause of neonatal mortality, accounting for 23% of neonatal deaths. An early intervention program (EIP) could improve neuro-developmental outcomes in survivors of birth asphyxia, but its feasibility in low-income countries has not been tested.  In this pilot study in Zambia, eighty live-born infants &#62; 1500 g of weight who had birth asphyxia and received resuscitation with bag and mask were enrolled for a study of standard care or EIP. Mothers/babies pairs were randomized into control (standard care) and intervention (EIP) groups and were followed up at home on a bi-weekly basis from 8 weeks to 8 months of age. Forty two mothers/babies (52.5%) completed the study at 8 months. Reasons for not completing the study were: 19 (50.1%) were lost to follow up, 16 (42.1%) withdrew, and 3 (7.8%) died. Follow-up to 8 months of age was not feasible for the majority in a large urban city with a low income population. Thus, interventions for children who have suffered birth asphyxia that require additional health care visits may not be currently feasible in the setting tested. There is a need to conduct further EIP studies to determine ways to improve follow up rates of children surviving birth asphyxia. Integrating early intervention programs with other successful health programs, such as the existing immunization programs, may improve follow up rates

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis

Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10–17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3. Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3. This decline was observed across all regions, in males and females. Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood