ABSTRACT
BACKGROUND: Children and adolescents with HIV taking antiretroviral therapy (ART) have high rates of viraemia. We assessed if genotypic resistance testing (GRT) to inform onward treatment improved treatment outcomes in Lesotho and Tanzania, two countries with little access to GRT. METHODS: The Genotype-Informed Versus Empirical Management of Viremia (GIVE MOVE) open-label, parallel-group randomised controlled trial enrolled children and adolescents with HIV between the ages of 6 months and 19 years, taking ART, and with a viral load at least 400 copies per mL. Participants were recruited from ten clinical centres and hospitals in Lesotho and Tanzania. Participants were electronically randomly allocated 1:1 to receive either GRT with expert recommendation (GRT group) or repeat viral-load testing and empirical onward treatment (usual care group). Participants and study staff were not masked, but the endpoint committee and laboratory staff conducting viral-load testing were. Participants in both groups received at least three sessions of enhanced adherence counselling, and in the GRT group, blood for GRT assessed via Sanger sequencing was drawn at enrolment. The composite primary endpoint was death, hospitalisation, a new WHO HIV clinical stage 4 event, or not having documented viral suppression of less than 50 copies per mL at 36 weeks in the modified intention-to-treat population, which excluded participants who were retrospectively found to be ineligible after randomisation. Serious adverse events were analysed in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT04233242) and the trial status is completed. FINDINGS: Between March 3, 2020, and July 5, 2022, 286 participants were enrolled and 284 were included in the modified intention-to-treat analysis (144 in the GRT group and 140 in the usual care group). Of these participants, 158 (56%) were female and 126 (44%) were male. Five (3%) in the GRT group and four (3%) in the usual care group did not complete follow-up but were included in the primary analysis. The median age across both groups was 14 years (IQR 9-16). The composite primary endpoint occurred in 67 (47%) participants in the GRT group and 73 (52%) in the usual care group (adjusted odds ratio 0·79 [95% CI 0·49 to 1·27]; adjusted risk difference -0·06 [95% CI -0·17 to 0·06]; p=0·34); all participants reaching the composite primary endpoint had no documented viral suppression at 36 weeks. No deaths were recorded, and only one clinical stage 4 event requiring hospitalisation occurred (in the usual care group); this was the only serious adverse event recorded in the study. INTERPRETATION: GRT-informed management did not significantly improve treatment outcomes for children and adolescents with viraemia while taking ART. FUNDING: Fondation Botnar, Swiss National Science Foundation, and Gottfried and Julia Bangerter-Rhyner Foundation. TRANSLATIONS: For the Sesotho and Swahili translations of the abstract see Supplementary Materials section.
Subject(s)
HIV Infections , Viremia , Humans , HIV Infections/drug therapy , Male , Female , Tanzania/epidemiology , Adolescent , Lesotho , Child , Viremia/drug therapy , Child, Preschool , Viral Load , Infant , Drug Resistance, Viral , Anti-HIV Agents/therapeutic use , Young Adult , Treatment OutcomeABSTRACT
BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. FINDINGS: The study population included 16â958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). INTERPRETATION: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. FUNDING: National Institute of Health Fogarty International Center.
Subject(s)
HIV Infections , Humans , Adolescent , HIV Infections/drug therapy , HIV Infections/mortality , Child , Retrospective Studies , Female , Male , Child, Preschool , Africa South of the Sahara/epidemiology , Infant , Young Adult , Infant, Newborn , Anti-HIV Agents/therapeutic useABSTRACT
Background: In global health, international nongovernmental organizations (NGOs) frequently hire, train, and partner with host-country clinicians who manage public outreach and patient care. Purpose and Research Design: We conducted a general interpretivist study of Basotho clinicians hired by NGOs and academic affiliates in Lesotho to identify cultural barriers and facilitators to community and patient education. Data Collection and Analysis: We conducted 13 interviews involving 16 participants (one physician, one nutritionist, 14 nurses). Using an inductive and iterative approach, we analyzed interview transcripts through the lens of social cognitive theory and identified 15 themes. Results: Major findings highlighted: 1) patient and community learners may view Basotho clinicians as authority figures; 2) family and community power dynamics affect healthcare access for vulnerable patient groups; and 3) village leaders may refuse community education when excluded from problem-solving and early planning. Conclusions: Although local clinicians and community members may identify with the same cultural group, clinicians can encounter cultural barriers to patient and community education.
Subject(s)
Garbage , Global Health , Humans , Lesotho , Qualitative Research , Group ProcessesABSTRACT
BACKGROUND: There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB. METHODS: Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020. Data were analyzed against a primary outcome of all-cause mortality with unadjusted Kaplan-Meier curves and Cox proportional hazard models. RESULTS: The study population included 774 CAHIV with variable intervals to ART initiation after starting TB treatment: <2 weeks (n = 266), 2 weeks to 2 months (n = 398), >2 months (n = 66), and no ART initiated (n = 44). Adjusted Cox proportional hazards models demonstrated increased mortality 1 year from TB treatment initiation in children never starting ART (adjusted HR [aHR]: 2.67; 95% CI: 1.03, 6.94) versus children initiating ART between 2 weeks and 2 months from TB treatment initiation. Mortality risk did not differ for the <2-weeks group (aHR: 1.02; 95% CI: .55, 1.89) versus the group initiating ART between 2 weeks and 2 months. CONCLUSIONS: This retrospective study demonstrated no increase in mortality among CAHIV initiating ART <2 weeks from TB treatment initiation. Given the broad health benefits of ART, this evidence supports the recent WHO recommendation for CAHIV to initiate ART within 2 weeks of initiating TB treatment.
Subject(s)
Anti-HIV Agents , HIV Infections , Tuberculosis, Pulmonary , Humans , Child , Adolescent , HIV , Retrospective Studies , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/drug therapy , Anti-Retroviral Agents/therapeutic use , Proportional Hazards Models , Anti-HIV Agents/therapeutic useABSTRACT
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 <3 years in North America and Europe to >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.
Subject(s)
HIV Infections , Adolescent , Adult , CD4 Lymphocyte Count , Child , Child, Preschool , Cohort Studies , Female , Growth Disorders/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Income , MaleABSTRACT
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.
Subject(s)
Capacity Building , Delivery of Health Care , Humans , Lesotho , Qualitative ResearchABSTRACT
As North American hospitals serve increasingly diverse patient populations, including recent immigrants, refugees, and returned travelers, all pediatric hospitalists (PHs) require foundational competency in global health, and a subset of PHs are carving out niches focused in global health. Pediatric hospitalists are uniquely positioned to collaborate with low- and middle-income country clinicians and child health advocates to improve the health of hospitalized children worldwide. Using the 2018 WHO standards for improving the quality of care for children and adolescents worldwide, we describe how PHs' skills align closely with what the WHO and others have identified as essential elements to bring high-quality, sustainable care to children in low- and middle-income countries. Furthermore, North American global health hospitalists bring home expertise that reciprocally benefits their home institutions.
Subject(s)
Culturally Competent Care/standards , Evidence-Based Practice/standards , Global Health/standards , Hospital Medicine/standards , Hospitals, Pediatric/standards , Pediatrics/standards , Practice Guidelines as Topic , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , International Cooperation , Male , World Health OrganizationABSTRACT
PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), continues to affect individuals, communities, and health systems worldwide. Here, we highlight how COVID-19 threatens to jeopardize the tremendous gains made over the last few decades on improving children's health globally. RECENT FINDINGS: In contrast to adults, children with COVID-19 are less likely to develop severe disease requiring hospitalization or die as a direct result of infection. However, the pandemic will likely have other important health impacts disproportionately affecting vulnerable children globally. Possible effects include worsening of poverty and food insecurity; disruption of already strained routine child health services; damage to already imperiled healthcare workforces; a wave of mental health challenges; interruption of education; and increased risks of violence, abuse, exploitation, and neglect. These challenges notwithstanding, the response to COVID-19 may also provide opportunities, such as for health system strengthening, that could improve child health after the pandemic. SUMMARY: The negative impacts of COVID-19 on global child health may be substantial. However, these are not foregone conclusions and much can be done to mitigate the worst outcomes. Child health providers should advocate for an equitable response to COVID-19 that prioritizes the health of vulnerable children and furthers the gains made in global child health.
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OBJECTIVES: The WHO recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high-burden TB/HIV countries. DESIGN: Retrospective longitudinal cohort. METHODS: We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted. RESULTS: Twenty thousand seven hundred and six patients collectively had 316â740 clinic visits, of which 240â161 (75.8%) had documented TB symptom screens. There were 35â701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4--64.0) and 88.8% (95% CI 88.7--88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7--17. CONCLUSION: Although specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.
Subject(s)
HIV Infections , Tuberculosis, Pulmonary , Adolescent , Africa/epidemiology , Botswana , Child , Eswatini , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/epidemiology , Humans , Malawi , Mass Screening , Retrospective Studies , Tanzania , Uganda/epidemiologyABSTRACT
BACKGROUND: 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). METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .
Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV/drug effects , Adolescent , Anti-HIV Agents/therapeutic use , Child , Child, Preschool , Cost-Benefit Analysis , Counseling , Female , Genotype , Herpes Genitalis , Humans , Infant , Lesotho , Longitudinal Studies , Male , Tanzania , Treatment Failure , Viral Load , Viremia/drug therapy , Viremia/virologySubject(s)
Betacoronavirus , Child Health , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Poverty , COVID-19 , Child , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Developing Countries , Global Health , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Risk Factors , SARS-CoV-2ABSTRACT
OBJECTIVE: To determine mortality and immune status improvement in HIV-infected pediatric patients on antiretroviral treatment (ART) in Malawi, Lesotho, and Swaziland. METHODS: We conducted a retrospective cohort study of patients aged <12 years at ART initiation at 3 sites in sub-Saharan Africa between 2004 and 2009. Twelve-month and overall mortality were estimated, and factors associated with mortality and immune status improvement were evaluated. RESULTS: Included in the study were 2306 patients with an average follow-up time on ART of 2.3 years (interquartile range 1.5-3.1 years). One hundred four patients (4.5%) died, 9.0% were lost to follow-up, and 1.3% discontinued ART. Of the 104 deaths, 77.9% occurred in the first year of treatment with a 12-month mortality rate of 3.5%. The overall mortality rate was 2.25 deaths/100 person-years (95% confidence interval [CI] 1.84-2.71). Increased 12-month mortality was associated with younger age; <6 months (hazard ratio [HR] = 8.11, CI 4.51-14.58), 6 to <12 months (HR = 3.43, CI 1.96-6.02), and 12 to <36 months (HR = 1.92, CI 1.16-3.19), and World Health Organization stage IV (HR = 4.35, CI 2.19-8.67). Immune status improvement at 12 months was less likely in patients with advanced disease and age <12 months. CONCLUSIONS: Despite challenges associated with pediatric ART in developing countries, low mortality and good treatment outcomes can be achieved. However, outcomes are worse in younger patients and those with advanced disease at the time of ART initiation, highlighting the importance of early diagnosis and treatment.
Subject(s)
Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/mortality , CD4 Lymphocyte Count , Child , Child, Preschool , Eswatini/epidemiology , Female , HIV Infections/immunology , Humans , Infant , Lesotho/epidemiology , Malawi/epidemiology , Male , Nutritional StatusABSTRACT
BACKGROUND: Children are largely underrepresented among those accessing treatment of HIV infection in Africa. Reported outcomes of children enrolled in national care and treatment programs are needed to inform the widespread scale-up of pediatric HIV care in resource-limited settings. METHODS: The objective of this article is to report on the early outcomes of a pediatric HIV infection care and treatment program in Lesotho during its first 14 months of operation. Clinical protocols are described, and characteristics and outcomes of the first cohort of children enrolled in care are reported, derived from a retrospective review of medical records. RESULTS: In the program's first 14 months, 1566 children and adolescents aged between 0 and 16 years were evaluated for HIV, with 567 (36%) confirmed to be infected. Of infected patients, 61% presented with advanced or severe symptoms of HIV disease and 65% presented with CD4 profiles consistent with advanced or severe immunodeficiency, based on World Health Organization 2006 guidelines. Two hundred and eighty four children received highly active antiretroviral therapy. The mortality rate was 18.6 deaths per 100 patient years of follow-up. Ninety-nine percent of deaths occurred within 90 days of enrollment. Deceased patients were significantly younger, had higher rates of stunting and wasting, and were more likely to present with low CD4 cell counts. CONCLUSION: Highly active antiretroviral therapy was well tolerated, but the early mortality rate was high despite concurrent management of HIV and comorbidities. Given that hundreds of thousands of children remain without access to HIV care, renewed efforts are needed to reach this underserved population.