Retention and adherence: global challenges for the long-term care of adolescents and young adults living with HIV

Purpose of review Adolescents living with HIV are the only age group with increasing HIV mortality at a time of global scale-up of access to antiretroviral therapy (ART). As a ‘treat all’ strategy is implemented worldwide, it is critically important to optimize retention and adherence for this vulnerable group. Recent findings Adolescents and young adults living with HIV have poorer outcomes when compared with adults at each stage of the HIV care cascade, irrespective of income setting. Rates of viral suppression are lowest for adolescents living with HIV, and adherence to ART remains an enormous challenge. High-quality studies of interventions to improve linkage to, and retention in, care on suppressive ART are starkly lacking for adolescents and young adults living with HIV across the globe. However, examples of good practice are beginning to emerge but require large-scale implementation studies with outcome data disaggregated by age, route of infection, and income setting, and include young pregnant women and key populations groups. Summary There is an urgent need for evidence-based interventions addressing gaps in the adolescent HIV care cascade, including supporting retention in care and adherence to ART

Global emerging resistance in pediatric infections with TB, HIV, and gram-negative pathogens

Infants, children and adolescents are at risk of life-threatening, antimicrobial-resistant infections. Global burdens of drug-resistant TB, HIV and gram-negative pathogens have a particular impact on paediatric age groups, necessitating a paediatric-focused agenda to address emerging resistance. Dedicated approaches are needed to find, successfully treat and prevent resistant infections in paediatric populations worldwide. Challenges include the diagnosis and identification of resistant infections, limited access to novel antimicrobials or to paediatric-friendly formulations, limited access to research and clinical trials and implementation challenges related to prevention and successful completion of treatment. In this review, the particular complexities of emerging resistance in TB, HIV and gram-negative pathogens in children, with attention to both clinical and public health challenges, are highlighted. Key principles of a paediatric-focused agenda to address antimicrobial resistance are outlined. They include quality of care, increasing equitable access to key diagnostics, expanding antimicrobial stewardship and infection prevention across global settings, and health system strengthening. Increased access to research studies, including clinical trials, is needed. Further study and implementation of care models and strategies for child- or adolescent-centred management of infections such as HIV and TB can critically improve outcome and avoid development of resistance. As the current global pandemic of a novel coronavirus, SARS-CoV-2, threatens to disrupt health systems and services for vulnerable populations, this is a critical time to mitigate against a potential surge in the incidence of resistant infections

Traversing the cascade: urgent research priorities for implementing the 'treat all' strategy for children and adolescents living with HIV in sub-Saharan Africa

Children and adolescents living with HIV (CALHIV) in sub-Saharan Africa experience significant morbidity and alarmingly high mortality rates due to critical gaps in the HIV care cascade, including late diagnosis and initiation of treatment, as well as poor retention in care and adherence to treatment. Interventions to strengthen the adult HIV care cascade may not be as effective in improving the cascade for CALHIV, for whom specific strategies are needed. Particular attention needs to be paid to the contexts of sub-Saharan Africa, where more than 85% of the world's CALHIV live. Implementing the 'treat all' strategy in sub-Saharan Africa requires dedicated efforts to address the unique diagnosis and care needs of CALHIV, in order to improve paediatric and adolescent outcomes, prevent viral resistance and reduce the number of new HIV infections. We consider the UNAIDS 90-90-90 targets from the perspective of infants, children and adolescents, and discuss the key challenges, knowledge gaps and urgent research priorities for CALHIV in implementation of the 'treat all' strategy in sub-Saharan Africa

Clinical Features of Critical Coronavirus Disease 2019 in Children

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objectives: We sought to describe the presentation, course, and outcomes of hospitalized pediatric coronavirus disease 2019 patients, with detailed description of those requiring mechanical ventilation, and comparisons between critically ill and noncritical hospitalized pediatric patients. Design: Observational cohort study. Setting: Riley Hospital for Children at Indiana University Health in Indianapolis in the early weeks of the coronavirus disease 2019 pandemic. Patients: All hospitalized pediatric patients with confirmed coronavirus disease 2019 as of May 4, 2020, were included. Interventions: Patients received therapies including hydroxychloroquine, remdesivir, tocilizumab, and convalescent serum and were managed according to an institutional algorithm based on evidence available at the time of presentation. Measurements and Main Results: Of 407 children tested for severe acute respiratory syndrome-coronavirus 2 at our hospital, 24 were positive, and 19 required hospitalization. Seven (36.8%) were critically ill in ICU, and four (21%) required mechanical ventilation. Hospitalized children were predominantly male (14, 74%) and African-American or Hispanic (14, 74%), with a bimodal distribution of ages among young children less than or equal to 2 years old (8, 42%) and older adolescents ages 15–18 (6, 32%). Five of seven (71.4%) of critically ill patients were African-American (n = 3) or Hispanic (n = 2). Critical illness was associated with older age (p = 0.017), longer duration of symptoms (p = 0.036), and lower oxygen saturation on presentation (p = 0.016); with more thrombocytopenia (p = 0.015); higher C-reactive protein (p = 0.031); and lower WBC count (p = 0.039). Duration of mechanical ventilation averaged 14.1 days. One patient died. Conclusions: Severe, protracted coronavirus disease 2019 is seen in pediatric patients, including those without significant comorbidities. We observed a greater proportion of hospitalized children requiring mechanical ventilation than has been reported to date. Older children, African-American or Hispanic children, and males may be at risk for severe coronavirus disease 2019 requiring hospitalization. Hypoxia, thrombocytopenia, and elevated C-reactive protein may be useful markers of critical illness. Data regarding optimal management and therapies for pediatric coronavirus disease 2019 are urgently needed.This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (grant numbers K23 HD095778, T32 HD069047); and by the National Institute of Allergy and Infectious at the National Institutes of Health Diseases (grant number T32 AI07637). Drs. Bhumbra, Malin, Khaitan, John, Rowan, and Enane disclosed off-label use of remdesivir, convalescent plasma, hydroxychloroquine, and tocilizumab. Drs. Kirkpatrick and Enane are supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (grant numbers K23 HD095778, T32 HD069047). Dr. Bhumbra is supported by the National Institute of Allergy and Infectious at the National Institutes of Health Diseases (grant number T32 AI07637)

"We did not know what was wrong"-Barriers along the care cascade among hospitalized adolescents with HIV in Gaborone, Botswana

High mortality among adolescents with HIV reflects delays and failures in the care cascade. We sought to elucidate critical missed opportunities and barriers to care among adolescents hospitalized with HIV at Botswana's tertiary referral hospital. We enrolled all HIV-infected adolescents (aged 10-19 years) hospitalized with any diagnosis other than pregnancy from July 2015 to January 2016. Medical records were reviewed for clinical variables and past engagement in care. Semi-structured interviews of the adolescents (when feasible) and their caregivers explored delays and barriers to care. Twenty-one eligible adolescents were identified and 15 were enrolled. All but one were WHO Clinical Stage 3 or 4. Barriers to diagnosis included lack of awareness about perinatal HIV infection, illness or death of the mother, and fear of discrimination. Barriers to adherence to antiretroviral therapy included nondisclosure, isolation, and mental health concerns. The number of hospitalized HIV-infected adolescents was lower than expected. However, among those hospitalized, the lack of timely diagnosis and subsequent gaps in the care cascade elucidated opportunities to improve outcomes and quality of life for this vulnerable group

“A problem shared is half solved” – A qualitative assessment of barriers and facilitators to adolescent retention in HIV care in western Kenya

Adolescents living with HIV (ALHIV, ages 10-19) are retained in care at low rates, resulting in poor clinical outcomes. We sought to define barriers and facilitators to retention experienced by perinatally-infected ALHIV in western Kenya. This qualitative study purposefully sampled hospitalized ALHIV (both engaged and not currently engaged in care), ALHIV engaged in outpatient care, and caregivers of ALHIV. In total, 116 ALHIV and caregivers participated in interviews or focus group discussions. Complex challenges related to the effects of both stigma and poverty at multiple socio-ecological levels pose the greatest barriers to adolescent retention in HIV care. Adolescents with positive relationships with family, clinic, and/or peers with the resources to support their care are facilitated to overcome these barriers. Conversely, adolescents with few of these supports due to orphanhood, caregiver illness, severe poverty, family conflicts, negative relationships with healthcare workers, or isolation, have the greatest challenges staying in care, and may be at risk of disengagement. Emerging from narratives of disengagement are experiences of trauma, which contribute to isolation, mental health challenges, and difficulties engaging in care. Retention of the most vulnerable adolescents will require interventions to mitigate the impacts of stigma, poverty, mental health issues, and limited social support on their engagement in HIV care

Ethical considerations for research involving pregnant women living with HIV and their young children: a systematic review of the empiric literature and discussion

Background: The proper and ethical inclusion of PWLHIV and their young children in research is paramount to ensure valid evidence is generated to optimize treatment and care. Little empirical data exists to inform ethical considerations deemed most critical to these populations. Our study aimed to systematically review the empiric literature regarding ethical considerations for research participation of PWLHIV and their young children. Methods: We conducted this systematic review in partnership with a medical librarian. A search strategy was designed and performed within the following electronic databases: Ovid MEDLINE, Embase and CINAHL. We screened titles and abstracts using the following inclusion criteria: (1) a study population of PWLHIV or children under 5 years of age; and (2) collection of qualitative or quantitative data regarding ethics of research participation. Excluded were reviews, commentaries, policy statements, clinical care-related ethics concerns, abstracts, case studies, or studies unrelated to HIV research. Studies were appraised for quality, data were extracted, and studies were qualitatively analyzed using a principle-based ethical framework within the Belmont Report. Results: Of the 7470 titles identified, 538 full-text articles were reviewed for eligibility and only three articles met full criteria for inclusion within this review. While we allowed for inclusion of studies involving young children born to mothers with HIV, only articles focused on PWLHIV were identified. Within the results of these studies, four themes emerged: (1) adequacy of informed consent; (2) consideration of paternal involvement; (3) balancing risks; and (4) access to research and treatment. A strength of this review is that it included perspectives of international research investigators, community leaders, and male partners. However, only two studies collected empiric data from PWLHIV regarding their experiences participating in research CONCLUSION: Researchers and funding agencies should be aware of these considerations and appreciate the value of and critical need for formative research to ensure clinical trials involving PWLHIV promote ethical, well-informed research participation and, ultimately, improve care outcomes. More research is needed to create a comprehensive ethical framework for researchers when conducting studies with PWLHIV

The Impact of Tuberculosis on the Well-Being of Adolescents and Young Adults.

The health needs of adolescents and young adults (AYAs) have been neglected in tuberculosis (TB) care, control, and research. AYAs, who are distinct from younger children and older adults, undergo dynamic physical, psychological, emotional, cognitive, and social development. Five domains of adolescent well-being are crucial to a successful transition between childhood and adulthood: (1) Good health; (2) connectedness and contribution to society; (3) safety and a supportive environment; (4) learning, competence, education, skills, and employability; and (5) agency and resilience. This review summarizes the evidence of the impact of TB disease and treatment on these five domains of AYA well-being

Impact of the COVID-19 pandemic on TB services at ART programmes in low- and middle-income countries: a multi-cohort survey.

INTRODUCTION COVID-19 stretched healthcare systems to their limits, particularly in settings with a pre-existing high burden of infectious diseases, including HIV and tuberculosis (TB). We studied the impact of COVID-19 on TB services at antiretroviral therapy (ART) clinics in low- and middle-income countries. METHODS We surveyed ART clinics providing TB services in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in Africa and the Asia-Pacific until July 2021 (TB diagnoses until the end of 2021). We collected site-level data using standardized questionnaires. RESULTS Of 46 participating ART clinics, 32 (70%) were in Africa and 14 (30%) in the Asia-Pacific; 52% provided tertiary care. Most clinics (85%) reported disrupted routine HIV care services during the pandemic, both in Africa (84%) and the Asia-Pacific (86%). The most frequently reported impacts were on staff (52%) and resource shortages (37%; protective clothing, face masks and disinfectants). Restrictions in TB health services were observed in 12 clinics (26%), mainly reduced access to TB diagnosis and postponed follow-up visits (6/12, 50% each), and restrictions in TB laboratory services (22%). Restrictions of TB services were addressed by dispensing TB drugs for longer periods than usual (7/12, 58%), providing telehealth services (3/12, 25%) and with changes in directly observed therapy (DOT) (e.g. virtual DOT, 3/12). The number of TB diagnoses at participating clinics decreased by 21% in 2020 compared to 2019; the decline was more pronounced in tertiary than primary/secondary clinics (24% vs. 12%) and in sites from the Asia-Pacific compared to Africa (46% vs. 14%). In 2021, TB diagnoses continued to decline in Africa (-8%) but not in the Asia-Pacific (+62%) compared to 2020. During the pandemic, new infection control measures were introduced or intensified at the clinics, including wearing face masks, hand sanitation and patient triage. CONCLUSIONS The COVID-19 pandemic led to staff shortages, reduced access to TB care and delays in follow-up visits for people with TB across IeDEA sites in Africa and the Asia-Pacific. Increased efforts are needed to restore and secure ongoing access to essential TB services in these contexts

'We are not going anywhere': a qualitative study of Kenyan healthcare worker perspectives on adolescent HIV care engagement during the COVID-19 pandemic

Introduction: Adolescents living with HIV (ALHIV) may be vulnerable to widescale impacts of the COVID-19 pandemic and to health system responses which impact HIV care. We assessed healthcare worker (HCW) perspectives on impacts of the COVID-19 pandemic on adolescent HIV care delivery and engagement in western Kenya. Methods: We performed in-depth qualitative interviews with HCW at 10 clinical sites in the Academic Model Providing Access to Healthcare in Kenya, from January to March, 2021. Semistructured interviews ascertained pandemic-related impacts on adolescent HIV care delivery and retention. Results: Interviews were conducted with 22 HCWs from 10 clinics. HCWs observed adolescent financial hardships, unmet basic needs and school dropouts during the pandemic, with some adolescents relocating to rural homes, to partners or to the street. Marked increases in adolescent pregnancies and pregnancy complications were described, as well as barriers to family planning and antenatal care. Transportation challenges and restrictions limited access to care and prompted provision of multi-month refills, refills at local dispensaries or transfer to local facilities. Adolescent-friendly services were compromised, resulting in care challenges and disengagement from care. Clinic capacities to respond to adolescent needs were limited by funding cuts to multidisciplinary staff and resources. HCW and youth peer mentors (YPMs) demonstrated resilience, by adapting services, taking on expanded roles and leveraging available resources to support adolescent retention and access to care. Conclusions: ALHIV are uniquely vulnerable, and adolescent-friendly services are essential to their treatment. The combined effects of the pandemic, health system changes and funding cuts compromised adolescent-friendly care and limited capacity to respond to adolescent needs. There is a need to reinforce adolescent-friendly services within programmes and funding structures. Support for expanded YPM roles may facilitate dedicated, scalable and effective adolescent-friendly services, which are resilient and sustainable in times of crisis