Primary and Acquired Immune Deficiency Disorders

35 Primary and Acquired Immune Deficiency Disorders

Wei Li Adeline Koay, Natella Rakhmanina, Megan Wilkins, Sarah Matthews, and Ami Doshi

nelson mandela

An AIDS-free generation would mean that virtually no child is born with HIV; that, as those children grow up, their risk of becoming infected is far lower than it is today; and that those who become infected can access treatment to help prevent them from developing AIDS and from passing the virus on to others.

anthony s. fauci

Introduction

This chapter describes the role of palliative care in improving the quality of life (QOL) of the immunosuppressed child and their family. Immunodeficiencies result from a failure of the immune system to function appropriately. Primary immunodeficiencies (PIDs) generally have genetic causes that disrupt the immune system, while secondary immunodeficiencies are acquired as a result of medications, malnutrition, infections (e.g., HIV), or other external factors. The major focus of this chapter is on lessons learned about caring for families of children, adolescents, and youth living with HIV (YLHIV), which serves as a prototype to address the wide range of problems encountered by children experiencing other immunodeficiencies and provides the reader with insight and skills to address areas of palliative care.

Immunodeficiencies caused by inherent defects in immunity affect up to 1 in 2,000 individuals in the United States,¹ and the 10-year survival after a PID diagnosis is 93.5% in one population-based cohort study.² More than 300 PIDs have been identified and are categorized into nine groups by the International Union of Immunological Societies (IUIS) PID expert committee according to their clinical and immunologic phenotypes (Table 35.1).³^,⁴ Survival of people living with PIDs has improved over the years with the advancement of medical research and novel treatment modalities, resulting in a growing population of individuals who live with a chronic medical condition that requires daily, complicated medical management, many of whom may benefit from palliative and end-of-life care programs.

Table 35.1 Characteristics of primary immunodeficiencies

Category	Examples of disorders	Inheritance	Selected clinical features	Treatment
Immunodeficiencies affecting cellular and humoral immunity	Severe combined immunodeficiency	XL	Severe infections, failure to thrive, rash, alopecia	Enzyme replacement, gene therapy, HSCT, immunoglobulin replacement, prophylactic antimicrobials
Immunodeficiencies affecting cellular and humoral immunity	Adenosine deaminase deficiency	AR	Cartilage abnormalities, deafness, cognitive defects
Combined immunodeficiencies with associated syndrome features	Wiskott Aldrich syndrome	XL	Recurrent bacterial and viral infections, diarrhea, eczema, lymphoma	Gene therapy, symptomatic management
	CHARGE syndrome	AD	Coloboma, heart defect, choanal atresia, intellectual disability, genital and ear anomalies, varying degrees of immune defects	Surgical intervention, hormonal replacement, thymic transplantation (clinical trial)
Predominantly antibody deficiencies	X-linked agammaglobulinemia	XL	Recurrent infections, chronic enteroviral meningoencephalitis	Prophylactic antimicrobials, immunoglobulin replacement, immunosuppressants
Predominantly antibody deficiencies	Common variable immunodeficiency	AD, no defect specified	Presents after 2 years of age, recurrent infections, granulomatous disease
Diseases of immune dysregulation	IPEX (immunodeficiency, polyendocrinopathy, enteropathy, X-linked)	XL	Autoimmunity, cytopenias, bacterial infections, eczema, diabetes	Immunosuppressants, biological agents, immunization, prophylactic antimicrobials
Diseases of immune dysregulation	Autoimmune Lymphoproliferative syndrome (ALPS)	AD, AR	Chronic adenopathy, splenomegaly, lymphomas
Congenital phagocytic defects	Shwachman-Diamond syndrome	AR	Pancytopenia, exocrine pancreatic insufficiency, chondrodysplasia	Prophylactic antimicrobials, interferon gamma infusion, G-CSF, HSCT (CGD), gene therapy
Congenital phagocytic defects	Chronic granulomatous disease (CGD)	XL, AR	Severe and recurrent infections
Defects in intrinsic and innate immunity	Anhidrotic ectodermal dysplasia	XL, AR, AD	Predisposition to invasive bacterial, parasitic, fungal and viral infections	HSCT, prophylactic antimicrobials, immunizations, immunoglobulin replacement
Autoinflammatory disorders	Familial Mediterranean fever	AR, AD	Abdominal pain, arthritis, recurrent fevers, vasculitis	Corticosteroids, immunosuppressants, biological agents, supportive
Autoinflammatory disorders	Neonatal-onset multisystem inflammatory disease	AD	Neonatal onset rash, chronic meningitis, arthropathy, deafness
Complement deficiencies	C5, C6, C7, C8a, C8b, C9 deficiency	AR, AD	Neisserial infection, recurrent pyogenic infections	Immunizations, prophylactic antimicrobials
Phenocopies of primary immunodeficiencies	ALPS-sFAS	Somatic mutations, autoantibodies	Presents later in life, hepatosplenomegaly, lymphadenopathy, autoimmunity, lymphoma	Immunosuppressants, immunoglobulin replacement

AD, autosomal dominant; ALPS, autoimmune lymphoproliferative syndrome; AR, autosomal recessive; CHARGE, coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, ear abnormalities; G-CSF, granulocyte colony-stimulating factor; HSCT, hematopoietic stem cell transplant; XL, X-linked; CGD, chronic granulomatous disease; IPEX, immnuodeficiency, polyendocrinopathy, enteropathy, X-linked.

Adapted with permission from Bousfiha A, Jeddane L, Picard C, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38(1):129–143; and Raje N, Dinakar C. Overview of immunodeficiency disorders. Immunol Allergy Clin North Am. 2015;35(4):599–623.

Secondary or acquired immunodeficiencies (Table 35.2) are more common than primary immunodeficiencies⁴^,⁵ and have a broad spectrum of clinical presentation depending on the underlying etiology and the host susceptibility. The most common secondary immunodeficiency, HIV, affected approximately 2.8 million children and adolescents globally in 2018, with 14.9 million children under the age of 18 years estimated to have lost one or both parents to acquired immune deficiency syndrome (AIDS)-related causes.⁶ Of the estimated 770,000 people who died of AIDS-related illnesses in 2018, approximately 15% of them were under 20 years of age.⁶ Vertically (or perinatally) acquired HIV is transmitted from the mother to the child during pregnancy, delivery, or breastfeeding, while horizontally acquired HIV is transmitted via blood transfusions (extremely rare in the United States), intravenous (IV) drug use, or through sexual contact. The latter is particularly important among adolescents, who constitute a significant proportion of horizontally acquired HIV in the United States.⁷ The scale-up of national preventive strategies, including universal prenatal HIV screening for pregnant women and replacing breastfeeding with formula feeding has resulted in a significant decrease in the number of perinatally HIV infected infants in the United States from approximately 1,630 in 1993 to 44 infants in 2016.⁷^,⁸ With early diagnosis and increased availability and use of antiretroviral therapy (ART), the mortality rate among children living with perinatally acquired HIV has reduced by up to tenfold compared to the period before ART became available.⁹

Table 35.2 Characteristics of secondary immunodeficiencies

Related causes of secondary immunodeficiencies	Examples
Medications	Immunosuppressants, corticosteroids
Procedures	Splenectomy, hematopoietic stem cell transplantation
Infections	HIV infection, cytomegalovirus, Epstein Barr virus
Metabolic conditions	Diabetes mellitus, uremia
Nutrition conditions	Malnutrition, vitamin deficiency
Protein losing conditions	Nephrotic syndrome
Hereditary/genetic conditions	Sickle cell disease, Trisomy 21
Miscellaneous conditions	Burns, malignancies, systemic lupus erythematosus

Adapted with permission from Chinen et al., 2010 and Raje et al., 2015.

Children with PIDs are usually diagnosed at a younger age compared to children with secondary immunodeficiencies, with the exception of infants with perinatal HIV infection who are diagnosed during infancy. Compared to children living with HIV who receive effective ART, children with PIDs tend to have earlier mortality, are at constant risk for opportunistic infections, and require more high-risk treatment interventions. As children with mild immunodeficiencies are less likely to require palliative care, this chapter focuses on palliative care for children living with severe immunodeficiencies. We specifically focus on YLHIV, acknowledging that physiological and psychological changes during adolescence are known to negatively impact HIV treatment outcomes and QOL.

Clinical Vignette

Daniel was the oldest of his mother’s children and was diagnosed with HIV as an infant, which was also when his mother learned of her own HIV status. She vigilantly brought him to his appointments and gave him medications for many years, but his medication adherence waned over time. Daniel had attention deficit hyperactivity disorder (ADHD) and reading difficulties as a child. His teenage years brought health concerns for his mother and also a struggle for independence for him. During this time, Daniel admitted to depressive symptoms, which were also in his family history and likely compounded by community violence and other environmental stressors. He worried about his mother’s declining health and watched her suffer through HIV-related renal failure and her complaints about dialysis. His mother eventually died when he was 12. Daniel showed increasing signs of depression over time, including social isolation, increased sleep, and irritability. When he was diagnosed with declining renal function himself, Daniel expressed concern about needing dialysis. He underwent a kidney transplant at age 16 and was fairly adherent to his post-transplant medications initially, but eventually showed signs of poor adherence and rejection. Once he turned 18, he expressed a desire to discontinue medications and dialysis. After graduating high school, Daniel made plans to reconcile and reconnect with his biological father, who lived in a nearby state. It was there that he chose not to take his medications any longer. Ethical concerns arose given his age, ADHD, and depression. An ethics consultation confirmed that Daniel was aware this decision might lead to his death, and he expressed the desire to see his mother again, in heaven, which he believed would happen should he die. Daniel also expressed that living with significant medical interventions, including the total number of medications taken daily and dialysis, was too much. Daniel was engaged with the palliative care team, who supported him and his family at the end of his life, primarily with pain management and facilitation of his end-of-life decisions and wishes. Daniel died at age 19 due to HIV-related renal failure, leaving behind his maternal grandmother, who cared for him after his mother’s death, and a younger brother, who was uninfected.

Physical Aspects of Care

Most children living with primary or secondary immunodeficiencies require lifelong treatment unless they have received curative treatments not available for the majority of these morbidities. As with all children, children with immunodeficiencies should receive routine immunizations, except for live vaccines in those with PIDs or AIDS. For all children and their household members, maintaining good hygiene is vital. However, children with immunodeficiencies should not be isolated or “kept in a bubble.”

With the advent and success of ART, most YLHIV on treatment are surviving into adolescence and adulthood. An estimated 50,900 youth had HIV in the United States in 2016,⁷ all of whom were recommended to take daily ART, ranging from single to multiple pills or multiple suspensions for young children. Adhering to ART can be challenging for caregivers, who often share the burden of the disease within the family, and for YLHIV who may not understand why they need to take medication or see their medical team regularly or who struggle with treatment fatigue or HIV-related stigma in their community. The US Department of Health and Human Services guidelines for care of YLHIV summarize recommendations for assessment and intervention strategies to support medication adherence.¹⁰ These guidelines and other meta-analyses of medication adherence in YLHIV suggest that medical providers assume a nonjudgmental approach to care, an example of which is the use of motivational interviewing strategies.¹¹ Routine assessment of medication adherence is recommended and, in addition to measurement of viral load, should also include one other type of measurement (e.g., self-report, pharmacy pill count, or pharmacy refill history assessment). Strategies to support adherence should be discussed at the initiation of therapy and at every medical visit thereafter. These strategies can take the form of regimen-specific changes (e.g., regimen simplification, reduction of pill burden) that could be offered, individual and family-level interventions (e.g., directly observed therapy, behavioral modification strategies, mobile phone applications), or healthcare provider–level interventions (e.g., providing multidisciplinary care, a youth-friendly environment and nonjudgmental approaches to discussion).¹⁰

Even though the life expectancy of YLHIV with effective ART in the United States has improved, with a 10-year survival rate of 94%,¹² living with HIV has long-term consequences on multiple organ systems including neurologic, cardiac, metabolic, and renal. YLHIV are not only at risk for bacterial infections, psychiatric diagnoses, and pain, but they also experience more subjective distress compared to their uninfected peers, including facing stigma, a sense of hopelessness, preoccupation with their illness, poor body image, and social withdrawal.¹³ Some chronic pain experienced by YLHIV is related to the side effects and toxicities of ART, which can cause abdominal discomfort, nausea, diarrhea, headaches, and neuropathy.¹⁴ With the introduction of new antiretroviral (ARV) drug classes, many older ARV drugs that were associated with more common toxicities are no longer in use. Side effects such as nausea and diarrhea typically resolve after the first few weeks of ART but may require antiemetics or antidiarrheal agents for symptom management. Insomnia and vivid dreams associated with certain regimens (e.g., efavirenz-based) can be abated by taking the ARV at bedtime and on an empty stomach. YLHIV with persistent symptoms for months or severe ART-related side effects can usually be managed by switching the presumed causative ARV for another agent, using ARVs with different side-effect and toxicity profiles when possible, or using dose reduction.¹⁰ Management strategies of ART-related side effects must be individualized for each child and in consultation with the primary team.

AIDS is the outcome of chronic HIV infection and a depletion of CD4 cells to levels below 200 cells/mcL or the presence of any “AIDS-defining” condition regardless of the CD4 cell count. AIDS can occur at a young age in children who have not received effective ART, either due to poor adherence to medications or a late diagnosis of HIV. AIDS-defining conditions include opportunistic infections and malignancies that occur as a result of immunosuppression.¹⁵ Clinical manifestations of poorly controlled HIV/AIDS in children include recurrent bacterial infections, neuro-psychiatric manifestations, malnutrition, respiratory problems, developmental delays, and pain (Box 35.1). Living with AIDS adds another layer of complexity to the management of YLHIV who require antimicrobial prophylaxis or treatment for opportunistic infections in addition to ART, which equates to requiring more daily medications and worse QOL.

Some YLHIV who initiate ART can develop an immune reconstitution inflammatory syndrome (IRIS), which manifests as a worsening of an opportunistic infection or new signs or symptoms and diagnosis of a previously occult opportunistic infection. The symptoms and opportunistic infections seen in people with IRIS are similar to those seen in people with AIDS. Although the data on IRIS in children are limited, a study in the United Kingdom showed that IRIS was relatively rare in children but was associated with a higher mortality rate compared to those who did not have IRIS.¹⁶ Given the potential impact of symptoms associated with HIV and complicating infections, pain and side effects associated with ART, and the psychological stress of adherence to these complex regimens on QOL for YLHIV,¹⁴ palliative care needs to be integrated with disease-directed care throughout the course of illness to improve QOL.

Structure and Processes of Palliative Care in HIV

In the past two decades, the trajectory of HIV in the setting of ART has shifted toward that of a chronic, incurable disease.¹⁷ Longer survival brings with it challenges of non–HIV-related illness, psychosocial impact, problems with medication adherence, and need for decision-making that were not present early in the course of HIV. The physical symptoms and psychosocial factors impacting YLHIV can be expected to endure, persist, and evolve over the course of their lifetime. YLHIV in many ways now embody the “gravely ill but long surviving” patients described as the typical patient base for pediatric palliative care.¹⁸ Despite recommendations to integrate palliative care into care of patients with HIV and evidence suggesting that palliative care improves psychosocial and physical outcomes,¹⁹^,²⁰ the improved survival with ART has drawn some focus away from palliative care in HIV.

The preferred model for pediatric palliative care is a blended model in which palliative care is integrated into the care of the child starting at the time of diagnosis of serious illness and throughout the illness, alongside restorative or curative care. HIV carries an uncertain prognosis and can make end of life difficult to predict. Minor health problems can potentially evolve into life-threatening events, and it is not uncommon for YLHIV to experience frequent life-threatening episodes. HIV may be considered a “life-threatening condition” in that it requires intensive life-long treatment aimed at maintaining QOL, and thus it is appropriate for palliative care to be part of the standard of care.²¹ HIV is a multigenerational disease where the child and parent(s) may witness each other’s death. Thus, HIV may invoke application of the entire spectrum of palliative care, from the perinatal period through bereavement support.

Regular assessment of goals of care is necessary for YLHIV,¹⁷ and older adolescents should be prepared to manage their own healthcare when approaching adulthood. Even when pediatric patients are successfully transitioned to an adult HIV clinic, there is a significant drop in retention over the first several years of adult care.²² Providers should strive for a comprehensive hand-off process to an adult HIV care team to ensure that the patient and family feel supported through this transition and to enhance retention in adult care.

Decision-making, advance care planning (ACP), and documentation of the youth’s and parent’s wishes are important aspects of palliative care to integrate throughout the course of illness. The vast majority of YLHIV wish to discuss end-of-life decision-making early in the course of their illness and prefer their doctor to initiate these discussions. Yet their parents are often unaware of these preferences, suggesting a need for better integration of palliative care.²¹ Facilitating communication between adolescents and their parents on these complex subjects represents a crucial area for intervention by the interdisciplinary care team. With HIV treatment teams representing a medical home for YLHIV and their families, patients and families may prefer early goals of care discussion to include or be initiated by the HIV care team or the primary palliative care team. Primary palliative care is palliative care provided by clinicians who are not palliative care specialists.²³ All clinicians caring for seriously ill patients, such as those with HIV, should have the skill set to perform some aspects of palliative care, such as basic symptom management, routine goals of care discussion, and referral to specialty-level palliative care or hospice.

YLHIV are typically supported by interdisciplinary teams. In pediatrics, the standard model is a family-centered model of an interdisciplinary HIV team which includes physicians, nurses, social workers, and mental health professionals, typically coordinated by an infectious disease specialist. Nutritionists, developmental specialists, and case managers are important members of the HIV team.¹⁷^,²⁴ Members of the HIV team may also include outreach coordinators and peer advocates. The HIV team will likely represent the front-line team supporting the child and family and be the provider of primary palliative care. As the HIV team will be highly engaged as the medical home for the YLHIV, they will provide significant psychosocial support and primary medical management of HIV.

Due to the inherent complexity of HIV, the palliative care team (Box 35.2) may be consulted to provide specialty-level palliative care. The success of HIV treatment and the resulting lower morbidity and mortality may mean that HIV clinicians today have less first-hand experience or comfort in providing specialty-level palliative care compared to the era of poorer prognosis. Specialty palliative care may be required in more complicated situations requiring complex symptom management or difficult decision-making.²³ The multigenerational nature of HIV, complex family dynamics, and potential substance abuse or other psychosocial concerns in caregivers all influence goals of care, decision-making processes, and grief in YLHIV. This creates situations in which the additional expertise of specialty palliative care can be beneficial. The palliative care team can provide assessment of complex pain and other non-pain symptoms²³ that may be underrecognized and can result from HIV, HIV treatment, and associated comorbid conditions. Given the importance of and challenges with medication adherence, the palliative care team may facilitate decision-making regarding ART and other potentially burdensome treatments and document these discussions. Reassessment of pain, QOL, and goals of care will be important throughout the illness given its unpredictable and evolving nature. It is imperative that the palliative care team keep hospital staff informed of the family’s understanding of illness and goals of care on an ongoing basis.

Box 35.2 Interdisciplinary Palliative Care Team

• Physicians focus on the illness trajectory, prognosis, and medical treatments, making patient visits or providing supervision in collaboration with advanced practice registered nurses or physician assistants.

• Nurses provide direct patient care, serving as patient advocate, care coordinator, and educator. Nurses are at the center of the immediate assessment and reassessment of patient needs.

• Advanced practice providers (physician assistants and advanced practice registered nurses) expand the capacity to deliver complex care and provide direct care.

• Social workers attend to family dynamics, assess and support coping mechanisms and social determinants of health, identify and facilitate access to resources, and mediate conflicts. In HIV, this may also include multigenerational impact, counseling regarding social stigma, addressing substance abuse.

• Chaplains, as the spiritual care specialists, assess and address spiritual and existential issues and help to facilitate continuity with the patient’s faith community as requested. Chaplains facilitate meaning-making and provide pre-bereavement support.

• Clinical pharmacists optimize medication management through a thorough review of the patient’s medications to identify therapies to further palliate symptoms, resolve or prevent potential drug-related toxicities, recommend dose adjustment, and de-prescribe where appropriate. In HIV, pharmacists are important in creating appropriate ART regimens.

• Mental health professionals assess and address depression, anxiety, substance use, and other mental health conditions and how they impact on medical care.

• Child life specialists address the child’s and siblings’ experience at developmentally appropriate level, providing assessment intervention and education. May facilitate meaning-making and memory-making; they provide coping mechanisms, especially for peer interaction and self-esteem in YLHIV.

Adapted with permission from Ferrell BR, Twaddle ML, Melnick A, Meier DE. National Consensus Project Clinical Practice Guidelines for Quality Palliative Care Guidelines, 4th edition. J Palliat Med. 2018; 21(12):1684–1689.²⁷

Care for YLHIV requires frequent medical appointments, developmental services, and in-home care, and it is often marked by frequent periods of acute illness and decompensation. An essential function of the palliative care team is to provide care coordination for a more seamless, family-centered experience. Children with immunodeficiency syndromes require complex care from a multitude of providers to manage the acute, chronic, and recurrent problems imposed by their underlying disorders. The presence of multiple existing clinical teams with competing priorities can create fragmentation and hamper effective communication. Improvement in the QOL for the child and family depends on the ability of interdisciplinary palliative care teams to collaborate with clinicians and subspecialists, schools, and community resources.

As with all palliative care, palliative care for YLHIV can be provided in all care settings: home, hospital, ambulatory, skilled nursing and assisted living facilities, and hospice. The goal is to provide palliative care in the setting that is preferred by and available to the child and family. Data in adults living with HIV suggest that embedding palliative care into the existing outpatient care of patients with HIV, via clinical training, teamwork, and availability of medications, favorably impacted on pain and symptom control and may represent a model for others to adopt.²⁵^,²⁶

Developmental Considerations

Children’s experience with HIV, their understanding of their condition, and their sources of psychological and spiritual distress evolve as they grow older. Special attention needs to be paid to the developmental stage of YLHIV in providing palliative care and initiating discussions of understanding the illness, goals of care, and coping. The team should determine the child or adolescent’s developmental status and parental preferences for communication with the child repeatedly throughout the trajectory of care, tailoring the assessment and intervention as developmentally appropriate.²⁷ Barriers to ART adherence change with age and developmental stage, ranging from palatability and tolerance of formulations in young children to social stigma and other concerns in adolescence. Understanding age-specific barriers is essential in creating strategies to promote adherence, which ultimately impacts QOL and mortality. Similarly, recommendations for disclosure of diagnosis also must account for the child’s developmental stage, acknowledging that the need for and response to disclosure may differ significantly between young children and adolescents.²⁸

Care for the Medical Team

Clinicians caring for YLHIV are reported to experience difficulty caring for these patients and their families. Common healthcare provider challenges include inadequate palliative care training, inadequate resources for symptom management, difficulty watching suffering from symptoms, a need to share feelings of distress, feelings of helplessness, and suggestions of burnout, among other factors.²⁹^,³⁰ Similarly, surveys of palliative medicine practitioners also indicate significant risk of burnout, particularly of emotional exhaustion.³¹^,³² Assessment of burnout and compassion fatigue should be conducted in palliative care and other clinicians caring for YLHIV and children with other immunodeficiencies. Strategies to address distress or promote well-being in clinicians could include peer support groups, multidisciplinary team meetings, palliative care rounds, creation of sustainable models of care, systematic opportunities to debrief after crises, and staff training and education.³³

Psychological and Psychiatric Aspects of Care

The cognitive and behavioral functioning of YLHIV is heavily impacted by the environmental conditions in which youth develop. YLHIV in the United States are at high risk for living in poverty,³⁴ which is associated with experiencing marginalization, community violence, suboptimal educational experiences, family instability, and other stressful life events. The negative impact of poverty and stressful life events on cognitive and mental health functioning has been well-documented for youth in general and for YLHIV.³⁵^,³⁶ A host of other issues can affect the behavioral and cognitive functioning of YLHIV, including social stigma, which is a complex social phenomenon that can include devaluation and stereotyping of an individual and is related to lower social support, increased risk for mental health symptoms, and poorer physical health in people with HIV.³⁷^,³⁸^,³⁹ Given the number of risk factors often present for YLHIV, stigma can be intersectional, sourcing from the youth’s primary medical diagnosis, their sexual or gender identity, race, or socioeconomic status, and it can contribute to increased risk for mental health diagnoses such as major depressive disorder and posttraumatic stress disorder (PTSD).

Historically, youth born with HIV were at risk for cognitive impairment due to viral impact on neurological functioning. This profound cognitive impairment observed was most often thought to be related to the presence of encephalopathy. More subtle impacts on cognitive functioning have been observed as advances in HIV treatment and detection have occurred, including executive functioning deficits, regardless of treatment patterns and medication adherence.⁴⁰^,⁴¹ Specifically, a pattern of slower processing speed and working memory deficits has been reported.⁴² On academic measures, YLHIV have not been found to perform lower than their uninfected counterparts on most measures, with the exception of youth with a history of encephalopathy and related profound cognitive impact, who perform significantly below the expected range for their age.⁴³ Among those with horizontally acquired HIV, cognitive impact has been reported, but treatment has not been shown to improve functioning over time.⁴¹ Youth may be at risk for academic struggle and thus exhibit less educational and vocational success than their age peers. However, research on decisional capacity among YLHIV with documented cognitive deficits supports the idea that most YLHIV have the decisional capacity to participate meaningfully in their palliative care and healthcare, including at the end of life, despite possible deficits in intellectual and/or adaptive skills.⁴⁴

YLHIV are at higher risk for psychiatric diagnoses, including anxiety disorders, mood disorders (e.g., depressive disorders), and ADHD.⁴⁵ When compared to youth exposed to but uninfected with HIV, rates of mental health disorders are similar,⁴⁶ suggesting environmental or other factors aside from HIV as contributing factors. While HIV status has not been strongly associated with mental health conditions,⁴⁶ the impact of mental health disorders on the treatment of HIV has been well-established. Depressive symptoms have been linked to poorer adherence and health outcomes.⁴⁷^,⁴⁸ Youth with mental health concerns may also be more likely to engage in risky sexual behaviors and less likely to disclose their illness status to partners.⁴⁹^,⁵⁰ Substance use, known to be more prevalent among youth with mental health conditions, may lead to decreased adherence to medication and HIV medical treatment. Compounded by increased risk for homelessness, trauma history, and marginalization due to sexuality, youth with horizontally acquired HIV have shown higher rates of substance use compared to their same-aged peers⁴⁹ and confer similar risks to their perinatally infected counterparts, including lower medication adherence rates and increased likelihood for engagement in risky sexual behaviors. Mental health disorders are underidentified and undertreated in this population, likely impacted by mental health stigma and the lower economic conditions already discussed. Providers need to be vigilant in screening for common mental health conditions, as well as for substance use and abuse, and refer appropriately to mental health providers for management when primary providers are unable to manage independently.

Social Aspects of Care

Stigma and discrimination are prevalent drivers of health outcomes for YLHIV and occur more frequently than in other health categories. Compared to people living with cancer, those living with HIV report more experiences of internalized shame, lower self-esteem, stigma including social rejection, social isolation, and financial insecurity associated with possible workplace discrimination.⁵¹ YLHIV may experience stigma based on their HIV diagnosis, sexuality, mental health condition(s), race, or other personal characteristics. Youth experience of stigma is often chronic, additive, and far-reaching in nature. Stigma impacts social, romantic, familial, and vocational aspects of their lives. Stigma influences youth decision to disclose their diagnosis, a uniquely personal decision. Youth may fear the negative impact disclosure will have on relationships, possibly burdening these youth with secrecy and emotional distance in social relationships. Furthermore, nondisclosure also negatively impacts on youth’s receipt of social support. Unintentional disclosure of diagnosis occurs when someone other than the youth themselves discloses their HIV diagnosis without their permission, thus impacting on the youth’s trust in others significantly. Providers should explicitly assure that all those present in the treatment room have awareness of the diagnosis through personal and private conversation with the identified patient and should communicate clearly about youth and family disclosure status when referring to outside medical providers.

Another unique social feature for YLHIV is an increased risk for parental loss or serious parental illness. This risk is related to the route of infection and multigenerational impact of HIV in families and communities. The impact of parental loss on child functioning is well-documented and includes further risk of mental health diagnoses and other psychosocial difficulties,⁵²^,⁵³ as well as risk for increased viral load.⁵⁴ As a result of this illness and/or death, youth may have more experience with death and the end-of-life experience. Youth may view their own HIV differently following the loss of a parent who has died from the same disease—losing hope regarding their own prognosis or shifting motivation to improve medication adherence to avoid worsening symptoms themselves. YLHIV who have lost their parents may also be less likely to have social support during treatment, including near the end of life. Youth with horizontally acquired HIV are at risk for low social support (given the aforementioned low disclosure rates due to stigma) and higher rates of marginalization from family due to sexuality or gender identity.⁵⁵

Cultural, Spiritual, Religious and Existential Aspects of Care

Cultural, Spiritual and Religious Aspects of Care

People living with primary and secondary immunodeficiencies come from diverse ethnic and cultural backgrounds, requiring the healthcare provider to take into account their patients’ particular cultures. Learning about a patient’s cultural beliefs and values allows the provider to be better equipped at helping the family and friends of their patients to adjust to end-of-life care and also improves the quality of medical care provided. For instance, it may be inappropriate and culturally insensitive in some cultures to discuss impending death, while some other cultures may express grief related to dying more openly. Culture, religion, and spirituality have a strong influence on decisions made by patients and their families and should be considered as part of the child’s care. From a pain management standpoint, this can be particularly challenging as some cultures do not accept or encourage the use of opioids, which are commonly used for pain relief.⁵⁶

Comprehensive palliative care for YLHIV requires attention to the spiritual domain through screening for spiritual or religious needs and identifying sources of support.²⁷ Indeed, YLHIV want their healthcare providers to inquire about their spirituality, especially in situations facing dying or chronic illness.⁵⁷ Literature suggests that spirituality in YLHIV, as in other chronic illnesses, may correlate with decreased depression and anxiety and improved QOL.⁵⁸ Positive spiritual coping appears to have a buffering effect against depression and poor coping strategies,⁵⁹ which may in turn impact adherence. No direct correlation between spirituality and adherence to ART has been shown,⁶⁰ although one study demonstrates that adolescents viewing HIV as a punishment demonstrated lower medication adherence.⁶¹ Religiousness has also been associated with higher likelihood of a higher symptom burden, especially pain,⁶² with the underlying reason being unclear. Meaning making is a key dimension of spirituality and fosters resilience. Throughout the course of the illness, YLHIV may carry a variety of beliefs surrounding their illness in an attempt to make meaning, including feeling “God’s presence,” feeling abandoned or punished by God, and being part of a larger force.⁵⁷^,⁵⁸ Clinicians should consider engaging a pastoral care provider for interested children and families to further explore and address their spiritual needs.

Resilience in End-of-Life Care

YLHIV demonstrate many patterns of resilience that are associated with better mental health and disease-specific outcomes. Coping mechanisms are an important factor in combatting HIV-related stressors and more generalized environmental stressors.⁶³ Coping self-efficacy, or the belief one has the ability to cope with a stressor, has been found to relate to resilience and decreased depressive symptoms.⁶⁴ Other factors that impact on youth resilience include self-esteem, perseverance, and positive parent–child relationships (e.g., active involvement and communication).⁶³^,⁶⁵ Similarly, social support from other adults in the life of youth reduces the risk of behavioral issues and increases coping efficacy.⁶⁶^,⁶⁷

Care of Refugees, Immigrants, and Children Who Are Adopted

A growing population of children living with HIV in the United States is comprised of immigrants, refugees, and internationally adopted children. According to the United States Department of Homeland Security, a refugee is a person who is unable to return to their home country due to “persecution or a well-founded fear of persecution on account of race, religion, nationality, membership in a particular social group, or political opinion.”⁶⁸ In 2017, more than 53,000 refugees were resettled in the United States, with children making up 46% of that number.⁶⁹ International adoptions by American families totaled just over 4,000 in 2018.⁷⁰ Some of the refugees and adopted children entering the United States each year are YLHIV, although data are not available regarding the exact percentage. Modes of transmission other than perinatal (i.e., blood transfusions, sexual abuse, substance abuse, transactional sex) may be more common in YLHIV born in other countries.⁷¹^,⁷² Furthermore, international adoptees have been found to suffer from comorbidities that are relatively rare in the US pediatric population, including tuberculosis, hepatitis, and congenital syphilis.⁷³ One study of HIV-infected international adoptees and refugees in foster care in the United States identified unique healthcare needs of this population, with many of these children experiencing stunting, gastrointestinal disease including parasitic infections and diarrhea, and mental health or behavioral problems.⁷⁴ Another study of YLHIV found that refugee children are less likely to have virologic suppression than non-refugee children.⁷⁵ Overall, children born in other countries may be diagnosed less promptly and have less access to healthcare resources, resulting in more comorbidities, opportunistic infections, and drug resistance.

YLHIV born in other countries also face unique psychosocial and cultural aspects of their illness. Refugees have endured trauma which forced them to flee their home country, putting them at risk for PTSD and other trauma-related disorders. Immigrants from other countries may have unique cultural views of HIV and medical and spiritual care and face language barriers and culture shock from being immersed in an entirely new system.

The following reflection demonstrates the challenges faced by a family who immigrated to the United States and the psychosocial issues that the adolescent faced after learning of her diagnosis.

Clinical Vignette

Donisha and her mother immigrated to the United States when she was 4 years old. Donisha had recurrent ear infections, which led to the development of bacterial endocarditis requiring an artificial heart valve at 6 years of age. During this time, Donisha tested positive for HIV. Her mother had tested negative for HIV in her home country and later learned that she was positive and had most likely passed the virus to her daughter. No one else knew of their HIV diagnosis at the time, and both mother and daughter did well initially with ART. However, Donisha’s mother passed away suddenly due to AIDS. Following her mother’s death, Donisha’s maternal grandmother brought her to clinic because of a clinic letter reminding her of a missed appointment. Until then, her grandmother did not know that Donisha and her mother had been living with HIV. The grandmother was overwhelmed and struggled with coping with the loss of her daughter and taking care of Donisha, so home nursing was arranged to assist her with Donisha’s care. Donisha had difficulty tolerating her HIV medications; she developed several complications and required feedings through a gastric tube at night. She gradually became overweight and developed obesity, but her HIV was relatively well controlled over the years. Her grandmother died in a car accident when Donisha was 15 years old. Donisha then had her third caregiver—her 72-year-old grandfather. He was warm and caring, but also struggled to support her. Gradually, Donisha’s obesity and depression became more prominent. She did not attend weight clinic or any fitness or diet programs recommended and arranged by her providers. She also refused to take any antidepressants or anticoagulants required for her artificial heart valve. At age 19 years, she had a boyfriend and kept her HIV a secret from him. She started smoking marijuana on a daily basis. Her immune status continued to worsen, and her lifestyle became increasingly sedentary. Through her HIV care team, she has begun to attend cooking classes where she met several young people living with HIV. During her meeting with her psychologist, she agreed to attend a peer support group, where transportation and food were provided. That experience has helped her to cope better with her HIV and comorbidities. She has an undetectable viral load for the first time in many years on treatment. What will happen to this young woman in the future? Will she find support in her partner? Will she be able to battle her substance use and depression? Or will she regress to being nonadherent to her medications? It is hard to know the future, but this young woman will continue to require support to stay on track. And that support must go well beyond the walls of the clinic into her community, home, and peer environment.