Consideraciones Psiquiátricas en ninos y adolescentes con VIH/sida

Estimados colegas comparto con ustedes este artículo sobre consideraciones psiquiatricas en ninos y adolescentes para su conocimiento, es tomada de un estudio realizado por Tami D Benton.

Saludos

Dr. Carlos Erazo

"Psychiatric Considerations in Children and Adolescents with HIV/AIDS


Tami D. Benton, MD

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Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, 3440 Market Street, Suite 410, Philadelphia, PA 19104, USA

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E-mail address:  bentont@email.chop.edu

A version of this article was previously published in the Child and Adolescent Psychiatric Clinics of North America, 19:2.

PII S0031-3955(11)00072-1

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The psychosocial impact of human immunodeficiency virus (HIV) disease has been recognized since the beginning of the epidemic for affected adults, but there has been less focus on the impact of HIV on young people. Among HIV-positive (HIV+) adults, high levels of distress, psychiatric symptoms, and their associations with worse health outcomes were recognized early in the epidemic. Subsequently, many studies have focused on understanding the prevalence of psychiatric symptoms among HIV+ adults and on identifying effective treatments for these symptoms. Fewer studies have examined these symptoms and their treatments among HIV+ children and adolescents. This article reviews what is known about psychiatric syndromes among HIV+ youths, their treatments, and other psychosocial factors of concern to the psychiatrist when treating children and adolescents with HIV disease.

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Keywords
	Human immunodeficiency virus
	Children
	Adolescents
	Psychiatric disorders

The psychosocial impact of human immunodeficiency virus (HIV) disease has been recognized since the beginning of the epidemic for affected adults, but there has been less focus on the impact of HIV on young people. Among HIV-positive (HIV+) adults, high levels of distress, psychiatric symptoms, and their associations with worse health outcomes were recognized early in the epidemic. Subsequently, many studies have focused on understanding the prevalence of psychiatric symptoms among HIV+ adults and on identifying effective treatments for these symptoms. Fewer studies have examined these symptoms and their treatments among HIV+ children and adolescents. This article reviews what is known about psychiatric syndromes among HIV+ youths, their treatments, and other psychosocial factors of concern to the psychiatrist when treating children and adolescents with HIV disease.

Epidemiology

Despite tremendous progress in our understanding of the HIV virus, its mode of transmission, and treatments to prevent its progression, HIV disease continues to be pandemic. Worldwide, an estimated 4.8 million people became newly infected in 2003 and more than 20 million people have died since the first cases of acquired immune deficiency syndrome (AIDS) were identified in 1981.^[1] An estimated 1,106,400 persons in the United States were living with HIV infection, with 21% undiagnosed and unaware of their infection at the end of 2006.^[2] In 2007, the estimated number of persons diagnosed with AIDS in the United States was approximately 37,041.

Most new HIV infections still occur among men who have sex with men (MSM). The Centers for Disease Control and Prevention (CDC) estimated that approximately 56,300 people were newly infected with HIV in 2006, with over half of these new infections occurred in gay and bisexual men. Black/African American men and women were strongly affected, and were estimated to have an incidence rate that was 7 times as high as that among whites.^[3] At the end of 2007, the estimated number of persons, adults and children, living with HIV/AIDS in the United States with confidential name-based HIV/AIDS infection reporting was 571,378. The estimated number of deaths of persons with AIDS in the United States through 2007 was 583,298.

Highly active antiretroviral therapies (HAART) and prenatal detection of HIV-infected women has caused the rates of congenitally acquired HIV to decline dramatically in developed countries, though rates remain high in less developed nations. Only 9300 cases of AIDS in children younger than 13 years were reported in the United States at the end of 2002, and only 59 cases of congenitally acquired cases were reported to the CDC in 2003.^[4] Since the advent of HAART, children acquiring HIV through vertical transmission are living longer and are now young adults, living with a chronic condition. Many of these young adults are attending college, are working, and are now beginning to have their own children.^[5]

Although new case rates for congenitally acquired HIV are low, many young people are acquiring HIV disease. Of new HIV infections reported to the CDC, adolescents account for 50% as well as 25% of new sexually transmitted diseases reported annually to the CDC.^[4] Infection rates among adolescents in the United States are increasing. The most common modes of transmission among adolescents and young adults was male to male sexual transmission, accounting for 42% of all cases; high-risk heterosexual contact accounted for 31%, and injection drug use 21%. The highest rates of new infections were among African Americans, and 19% were among Hispanics. HIV infection is a growing problem among adolescents, especially minority adolescents, emphasizing the importance of prevention efforts focused on the adolescent population.

Etiology of HIV/AIDS infection among youth

Infected mothers transmit HIV during pregnancy or delivery, or through breast milk. Person to person transmission occurs through blood contacts such as transfusions or needle sharing; or through sexual contact with an infected partner. Transmission through blood products is rare in the United States but prevalent in some other countries. Perinatal transmission of HIV has been significantly reduced by the implementation of voluntary routine prenatal screening for HIV implemented by the CDC in 2001,^[6] and the use of reverse transcriptase inhibitors in HIV+ pregnant women during the prepartum and intrapartum periods and during breast feeding. Recent revisions to the CDC's recommendations include voluntary testing in all health care settings for individuals aged 13 to 64 years. It is further recommended that individuals at risk for acquiring HIV disease and their sex partners be tested annually.^[6]

Once exposure to HIV has occurred, the virus infects helper T cells and replicates in the peripheral blood and lymphoid organs. The immune system responds by generating cytotoxic T lymphocytes (CTLs) that recognize and kill viral particles. The initial invasion and viremia may be experienced as a mild flu-like syndrome initially, but then the reduced viremia, resulting from the CTLs, produces a phase of clinical latency, an asymptomatic phase that can last for years. Unfortunately, the immune system eventually deteriorates with increased viremia, the development of symptoms, and eventually AIDS. AIDS is diagnosed when the CD4+CD3- count falls below 200 cells/mL or when one AIDS-defining condition occurs.

Early detection of HIV viral infection is critical to effective treatment. New technologies that allow earlier, quicker, and more accurate detection have been developed. For acquired HIV, rapid diagnostic tests using saliva can provide screening results in as little as 20 minutes. However, serum samples are still required to confirm the presence of HIV infection. These tests generally detect the virus or its antibody, 2 to 12 weeks after the initial infection, and include enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassay, Western blot, p24 antigen capture assay, HIV-1 DNA polymerase chain reaction (PCR), and HIV-1 RNA assay.^[7] HIV antibody detection, however, cannot be used to make a diagnosis of HIV disease in infants when vertical acquisition of HIV is suspected. Virologic testing to identify antibodies to the virus and its components, using DNA and RNA PCR, are made within the first 48 hours of birth, at 1 to 2 months, and again at 3 to 6 months to distinguish the infant antibodies from maternal antibodies, which should decline over time. Definitions for defining AIDS in the pediatric population are similar to those for adults, with some exceptions ( ^{[Table 1] , [Table 2]} ).^[8] Another classification system has been developed to include infants exposed to HIV whose status remains to be determined. The Baylor International Pediatric AIDS Initiative Education Resources provides a comprehensive description of these conditions.^[9]

Table 1   --  Revised human immunodeficiency virus pediatric classification system: immune categories based on age-specific CD4+ T-lymphocyte count and percentage

	Less Than 12 Months	1–5 Years	6–12 Years
Immune Categories	No./μL (%)	No./μL (%)	No./μL (%)
Category 1: no suppression	>1500 (>25%)	>1000 (>25%)	>500 (>25%)
Category 2: moderate suppression	750–1499 (15%–24%)	500–999 (15%–24%)	200–499 (15%–24%)
Severe suppression	<750 (<15%)	<500 (<15%)	<200 (15%)

Neurologic effects of HIV infection

HIV primarily infects microglia of the central nervous system and macrophages. Its neurotoxic effects are thought to result primarily from the virus's ability to induce inflammatory factors that result in neuronal cell damage and death. In the adult population, the late effects of the neuronal cell damage presents as HIV-associated dementia (HAD). In children and adolescents, 2 types of encephalopathies may be seen: (1) a progressive encephalopathy characterized by acquired microcephaly, loss of previously acquired skills, and corticospinal tract abnormalities, and (2) a static encephalopathy presenting with cognitive and motor delays, but without a loss of acquired skills or neurologic deficits.^[10] How the neurologic findings of a child or adolescent manifests clinically are related to many factors including length of infection, severity of deficits, rate of decline, and mode of transmission; for example, HIV encephalopathy is most commonly seen in those children and adolescents who were infected through vertical transmission.^[11] High rates of severe, progressive encephalopathy were commonly seen with pediatric HIV disease at the beginning of the epidemic (50%–90%); however, improved antiretroviral therapy reduces viral load, thus reducing the numbers of infected cells in the central nervous system (CNS) and slowing the progression of CNS disease.^[11] Current rates of HIV encephalopathy presenting with brain atrophy, cognitive delays, and motor deficits are much less common and estimated to be present in 13% to 23% of infected children.^[11] Findings associated with encephalopathy are increased calcifications of the basal ganglia, brain atrophy, enlarged ventricles, and enlarged cortical sulci.^[12] Recent studies further suggest that higher viral loads are associated with severity of cerebral atrophy and are not associated with the presence of intracerebral calcifications.^[13] Magnetic resonance imaging (MRI) studies have been recommended for children with progressive neurocognitive dysfunction, who do not exhibit symptoms of an AIDS-defining illness.^[14] MRI screening may detect mass lesions associated with lymphomas or toxoplasmosis, and cerebrovascular complications that are more commonly seen in HIV-infected adolescents.^[15]

Cognitive findings in HIV-infected children are generally characterized by impairments in expressive and receptive language skills, with expressive language commonly impacted more than receptive language, as well as frequent impairments in visuomotor skills and spatial learning.^[16]

HAD, which has been well described in adults, has not been described in adolescents. HAD, a subcortical dementia, presents with progressive cognitive decline, behavioral abnormalities, and motor dysfunction. The frontal-cortical thinning found in HAD has been associated with declining attention, executive functioning, and working memory.^[17] Although not well described in adolescents, case studies describing the presence of dementia in adolescents suggest that this syndrome may become a more frequent observation in the future as adolescents live longer with this chronic disease.^[18] For adolescents who are HIV+, a significant risk factor for the development of CNS disease is strongly related to adherence to HAART, which requires multiple daily dosing of multiple medications. Poor adherence to antiretroviral treatments with consequent suboptimal medication levels can lead to viral drug resistance, higher viral loads, and increased risk for CNS disease. For school-aged children and adolescents, cognitive impairments, particularly undetected cognitive deterioration, can lead to academic failure, impaired occupational functioning, and impaired capacity to adhere to treatment recommendations. At present, neurodevelopmental assessment and testing are recommended every 6 months for children younger than 2 years; once a year for children aged 2 to 8 years who are asymptomatic, and more often if symptomatic; and every 2 years for asymptomatic, stable children 8 years and older.^[19]

Among adolescents who acquire HIV through transfusions, needle sharing, or sexual contact, the use of antiretroviral therapies have increased the length of time lived with HIV. Long-term survivors are more likely to have problems with attention, memory, and other cognitive processes. Adolescents who develop AIDS may show late neurocognitive changes with progressive bradykinesia, spasticity, and hallucinations.^[20]

Psychiatric syndromes in children and adolescents with HIV disease

The recognition of psychiatric syndromes in HIV-uninfected adolescents and in HIV+ adolescents, and the use of available interventions when recognized are extremely important. A large body of evidence supports the associations between adolescents with mental health conditions and the greater risk for HIV transmission. Psychiatrically ill adolescents are more likely to be sexually active at an early age, to engage more often in unprotected intercourse, to have multiple sexual partners, ^{[21] , [22]} to have histories of sexually transmitted diseases, and to use drugs or alcohol when having sex, and are less likely to use a condom.^[5]

Recognizing psychiatric symptoms and other behavioral problems presenting in the context of HIV disease results from many complex and interacting factors, and it is important that the clinician understand how these factors might affect the child's or adolescent's presentation of emotional distress. The direct or indirect effects of the virus on the CNS, genetic factors, prenatal exposure to substances, opportunistic infections, adequacy of medical care, family and peer relationships, and other environmental factors affect the presentation of these symptoms. Another factor affecting the presentation of behavioral problems is that the majority of youngsters exposed to HIV face environmental stressors associated with living in demographically distressed areas affected by poverty, family stress, and alcohol and substance abuse.^[5]

Families living with HIV also face several unique challenges. Mothers with HIV frequently become aware of their own illness during their pregnancies and must come to accept the diagnosis of a chronic and ultimately fatal illness for themselves, while caring for their newborn infants. Parents living with HIV must adhere to demanding treatment regimens while parenting infected children, parenting their children who are not HIV+ (affected children), soliciting family and social support for their families in the face of stigma, facing decisions about disclosure of their HIV status, and planning for their own deaths and the future care for their children. Children living with HIV-infected parents must also face the burden of living with chronically ill parents, many of whom struggle with addictions or mental health conditions, who will eventually succumb to this ultimately fatal illness.

For children and adolescents living with HIV disease, many factors associated with their illness threaten their emotional well being: coping with the pain of their physical illness, worries about their physical health or prognosis, frequent disruptions of social and academic activities due to hospitalizations and medical appointments, social stigma and isolation, fears related to disclosure, losses, and concerns about their own body image related to wasting, lipodystrophy, or dermatologic conditions associated with their illness. For younger children, feelings of guilt for having done something wrong to deserve HIV are common. Feelings of depression, social withdrawal, loneliness, anger, and confusion are not uncommon among youths struggling to cope with HIV disease.

Prevalence rates of psychiatric disorders among HIV+ adolescents have varied widely due to differing study methodologies and study designs. Clinical reports suggest high rates of mental health problems in perinatally infected adolescents.^[23] Few well-controlled studies have examined prevalence rates of psychiatric disorders among adolescents who have vertically or behaviorally acquired HIV disease. ^{[24] , [25] , [26]}

In one study, Scharko^[24] reviewed published studies of the prevalence of psychiatric disorders among HIV-infected youth, finding only 8 studies that examined psychiatric disorders using Diagnostic and Statistical Manual (fourth edition; DSM-IV) criteria. These investigators found high prevalence rates of psychiatric disorders: 28.6% with attention-deficit/hyperactivity disorder (ADHD), 24.3% with anxiety disorders, and 25% with depression. Generalizability of this study is limited as data collected across studies had varying populations and sample sizes were small; modes of infection, diagnostic methods, age range of samples, and use of control groups varied. A controlled study of behavioral problems in perinatally infected children found high rates of behavioral problems, but they did not differ from those of a control group of children who were perinatally exposed but not infected with HIV, suggesting that HIV infection was not a contributor to the development of behavior problems.^[27] Another study found high rates of psychiatric hospitalizations among perinatally infected children and adolescents when compared with non-HIV–infected peers, with the primary admitting diagnosis being depression, ADHD, and oppositional defiance disorder (ODD).^[23] One small study of HIV-infected youth aged 6 to 15 years described high rates of depression (47%) and attentional problems (29%). These investigators suggested that depression might be associated with encephalopathy and worsening immune function.^[28]

In one of the few studies using a structured interview to obtain psychiatric diagnosis, Pao and Lyon^[25] used the SCID (Structured Clinical Interview for DSM-IV axis I Disorders) to evaluate 34 HIV+ adolescents attending an urban clinic, for current and lifetime rates of psychiatric disorders. The investigators found very high prevalence rates of lifetime psychiatric diagnosis. In this sample, 68% had a diagnosis of depression, 59% substance abuse, and 29% conduct disorder. It was further found that the majority of these youths had psychiatric disorders preceding their diagnosis, and that approximately half of them had a current affective disorder. These rates of disorders are significantly higher than those found among the general adolescent population whose rates of psychiatric disorders range between 10% and 22%. These data suggest that HIV+ adolescents have higher rates of depression, substance abuse, and conduct disorders.^[29] In another study using the Diagnostic Interview Schedule for Children (DISC-IV) to determine the presence of psychiatric disorders in 47 perinatally infected youths aged 9 to 16 years, 55% of youths evaluated met criteria for a psychiatric disorder, with anxiety disorders being most prevalent (40%), followed by ADHD (21%) and disruptive behavior disorders (24%).

Recent well-controlled studies of psychiatric diagnosis among perinatally acquired HIV+ youth suggests rates of psychiatric disorders ranging from 48%^[30] to 61%.^[26] These studies together support high rates of psychiatric illnesses among adolescents who have acquired their HIV infections both behaviorally and perinatally, further emphasizing the importance of the biopsychosocial approach in the evaluation and treatment of HIV-infected youth.^[31]

Treatment

Recommendations for pharmacologic treatment of psychiatric disorders in HIV-infected youth are largely empirical.^[5] Data obtained from adults suggest that medications commonly used to treat psychiatric symptoms in nonmedically ill individuals, including psychostimulants, antidepressants, and antipsychotic medications, are useful for the treatments of those disorders in the medically ill, including those who are HIV+.^[32]

However, when choosing to use psychotropic medications, careful consideration and caution should be used when prescribing these medications in HIV+ youths who are using HAART. Many psychotropic medications, as well as antiretroviral ones, are widely metabolized by the cytochrome P450 system, especially the subgroups 3A4 and 2D6, and have a high potential for drug-drug interactions ( ^{[Table 1] , [Table 2]} ). For medications that are metabolized by the liver, enzyme systems may be inhibited or stimulated by these medications, thus increasing or decreasing levels of one or both. Although the clinical significance of many of these interactions is unclear, certain classes of antiretrovirals are known to pose the greatest risk for changes in drug levels that are significant in HIV+ individuals. The protease inhibitors, specifically ritonavir, has the greatest impact on the inhibition of 3A4, and to a lesser extent on 2D6; Efavirenz has been shown to induce CYP3A4, which potentially decreases plasma levels of coadministered medications principally metabolized by this pathway.^[33]

Table 2   --  Common interactions of antiretroviral therapies and psychotropic medications

Drug Name	Interactions With HAART
Citalopram	Lopinavir/r, ritonavir increase citalopram levels
Fluoxetine and fluvoxamine	Increase levels of amprenavir, delavirdine, efavirenz, indinavir, lopinavir/r, nelfinavir, ritonavir, saquinavir Nevirapine decreases flluoxetine levels
Paroxetine	Lopinavir/r, ritonavir increase paroxetine levels
Sertraline	Lopinavir/r, ritonavir increase sertraline levels

Before considering psychotropic medication use for HIV+ children receiving antiretroviral therapies, factors beyond the presenting behavioral complaints must be evaluated and considered. Developmental, environmental, social, and family factors may influence the behavioral presentation, and must be considered. A comprehensive assessment including information from the child or adolescent, as well as collateral information from schools, primary care providers, specialists, counselors, family members, and others involved in caregiving should be compiled. A thorough family psychiatric history and histories of stressors is extremely important in reaching diagnostic conclusions.

Another consideration when prescribing for youths relates to the absence of evidence guiding psychotropic administration and dosing in this population. When choosing medications and dosing, the clinician must consider the child's weight, body mass index and Tanner stage, status of medical illness, potential drug interactions, and side effects of medications. When evidence of neurologic disease is present, the potential for medication side effects is even greater. It is important to start with low doses of medication, and to titrate slowly to minimize adverse effects that might decrease adherence.

Mood disorders: depression and bipolar disorder

The prevalence of depressive disorders increases in frequency from childhood to adolescence for HIV-negative (HIV-) and HIV+ populations.^[29] The presentation of depression in adolescents who are HIV+ is similar to adult populations. As in adults, depressed mood and irritability of at least 2 weeks' duration are criteria. Complicating this diagnosis of depression in the HIV+ child or adolescent, however, is the overlap between the vegetative symptoms of depression and the symptoms of the medical illness, or side effects of HIV treatments. Symptoms such as anorexia, fatigue, or other somatic complaints may be related to depression or HIV disease. When establishing the diagnosis, evaluation for worsening of medical status, poor adherence with resulting drug resistance, recent stressors with resulting adjustment disorder, or other psychological factors should be considered.

Although antidepressants of all classes have been prescribed to HIV+ children and adolescents based on the adult literature, selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications, though no evidence currently exists to support differences in efficacies. However, only fluoxetine has been approved for the treatment of depression in children older than 8 years, and has the greatest empirical support.^[34]Amitriptyline is approved for depression in patients older than 12 years. Tricyclic antidepressants (TCAs) have been used empirically to help with pain syndromes, insomnia, and anxiety, but their sedating side effects and potential for toxicity in overdose limits their usefulness.^[35] Fluoxetine, and its metabolite norfluoxetine, may inhibit CYP 3A3 and 3A4, contraindicating its use with macrolide antibiotics, azole antifungal medication, and several other medications.^[36]Citalopram and mirtazepine are commonly used because they have fewer drug interactions and more favorable side effect profiles. In addition, mirtazepine has been helpful in promoting weight gain and sleep. Careful monitoring for the emergence of suicidal ideation is warranted with the use of the medications during treatment.

The presence of bipolar disorder in prepubertal youth and adolescents, and its clinical presentation, has been supported by a large evidence base, although no studies have examined the prevalence of these disorders in HIV+ youth.^[37] The presence of grandiosity, elevated and expansive mood, racing thoughts, decreased need for sleep, and hypersexuality can also present in the pediatric population, and can occur with other childhood psychiatric disorders such as ADHD and substance abuse.^[38] Treatment recommendations for children and adolescents with bipolar disorder are similar to those recommended for adults,^[39] with the caveats that drug interactions, hepatotoxicity, and side effect profiles must be considered in the presence of HIV disease.

Attention-deficit/hyperactivity disorder

Several studies suggest high rates of ADHD in HIV-infected youths, ^{[24] , [40]} though few studies have examined the use of psychotropic medications in this group. The efficacy of psychostimulants for the treatment of ADHD in nonmedically ill populations is well validated, and is the pharmacotherapeutic treatment of choice for this disorder. Although commonly prescribed in HIV+ children, few studies exist that examine dosage or efficacy in the HIV+ population.

Empirical data suggest initiating treatment at the same dosages as those in the nonmedically ill population, and titrating those dosages as recommended. Stimulant medications have few drug-drug interactions, making them relatively safe in combination with antiretrovirals; however, it is important to observe for side effects.

Anxiety disorders

Anxiety disorders appear to be common among HIV+ youths, frequently comorbid with other psychiatric disorders. Social and specific phobias, separation anxiety disorders, agoraphobia, generalized anxiety, panic, and obsessive compulsive disorders have been reported, but the prevalence rates of specific anxiety disorders are unclear.^[26] When present in HIV+ youth and significant enough to interfere with normative function, cognitive and behavioral therapies are indicated. The use of SSRIs and TCAs have demonstrated some efficacy in cases of anxiety disorders that fail to respond to behavioral strategies.

Posttraumatic stress disorder

The epidemiology of HIV in United States women increases the risk of exposure to trauma for youth living with HIV. The majority of perinatally exposed youths live in inner cities where stress, poverty, and trauma are prevalent.^[41] Trauma related to traumatic events and trauma related to medical procedures place HIV+ youth at risk for posttraumatic stress disorder (PTSD) and/or traumatic stress.^[42] The evidence further suggests that trauma exposure may adversely affect adherence to treatment recommendations among HIV+ youth.^[43]

In one study examining the prevalence of PTSD and posttraumatic stress symptoms (PTSS) in a sample of HIV+ youth, 30 adolescents and young adults with HIV/AIDS were evaluated using a trauma symptoms checklist keyed to DSM-IV PTSD symptoms. The investigators found high rates of PTSD (13.3%) and PTSS (20%) in response to receiving a diagnosis of HIV infection. Even higher rates of PTSD and PTSS (23.3% and 23.3%) were observed when examining other traumatic events experienced by this same group of adolescents.^[43]

Treatment studies for adolescents with PTSD suggest that cognitive behavioral therapies focused on PTSD symptomatology are more effective than other therapies in the management of symptoms and that medications can be helpful, although support for medication use in adolescents are weak.^[44]

For children and adolescents experiencing anxiety related to procedures, benzodiazepines used in low doses, such as lorazepam, in conjunction with distraction techniques and psychotherapy have been helpful. Clonazepam has been used as an adjunct to psychotherapy for children and adolescents experiencing more pervasive and prolonged anxiety. Benzodiazepines may cause sedation and behavioral disinhibition, especially in patients with CNS disease, and should be monitored closely.^[45]

Antihistamines have been used to sedate anxious children, but are not recommended for the treatment of anxiety. In addition, the anticholinergic properties of antihistamines can precipitate or worsen delirium.^[45]

Delirium and dementia

The evidence suggests that delirium in the pediatric population presents with the same clinical picture as that of adults, and that the DSM-IV diagnostic criteria are applicable across the lifespan. Impairments in attention, responsiveness, levels of consciousness, orientation, confusion, affective lability, and sleep disturbance are present in pediatric patients with delirium, although paranoia, perceptual disturbances, and memory impairment are less common in younger children. The most common etiologies involve medical conditions.^[46]

Treatment recommendations for pediatric delirium have been based on those found in the adult literature, and consist of developmentally appropriate strategies to maintain orientation and to provide environmental cues that will be reassuring for the child. Low doses of atypical antipsychotic agents have been used empirically, although one case report suggests that the atypical agent risperidone failed to adequately address symptoms of delirium in an adolescent with HAD.^[18]

While the presence of HIV-associated dementia has been well described among adults with HIV disease, this late-appearing neuropsychiatric presentation has not been well described in the pediatric population.^[47] HIV-related progressive and static encephalopathies have been observed and described among perinatally infected youth.^[10] One case report of an adolescent presenting with delirium and HAD suggests that our conventional thinking about the presentation of HIV-associated dementia among youths may be changing as adolescents with perinatally acquired HIV and adolescents with behaviorally acquired HIV are living longer with this chronic illness.^[24]

Other psychosocial factors that may be a focus of clinical intervention

Adherence

Current treatments for HIV/AIDS use antiretroviral medications. Four classes of medications, each with different mechanisms of action, are used in combination with a protease inhibitor to prevent the entry, replication, and cell destruction caused by HIV: nucleoside analogue reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), fusion inhibitors, and protease inhibitors. These medications require multiple day dosing, have unpleasant side effects, require caution when used with other medications, and have potential for multiple drug interactions. To gain optimal benefit from these medications, compliance must be near 100%.^[48] Poor or inconsistent adherence can result in increasing viral loads, progression to AIDS, and the development of resistance to current therapies. The Reach study^[49] demonstrated the important relationships between psychiatric illness and adherence. These investigators examined longitudinal adherence to antiretroviral treatments among HIV+ adolescents for 1 year. Depression was associated with poor adherence to antiretroviral medications. At the initial study visit, 69% of the adolescents were adherent to medications by self-report, with only 50% being adherent at 12 months. Those with later stage disease were less adherent. Failure to maintain adherence was significantly associated with depression. Williams^[50] examined predictors of adherence, demographics, and psychosocial characteristics of a large cohort of HIV+ children and adolescents (vertically transmitted) and their caregiver participants in the Pediatric AIDS Clinical Trials Group. Among this cohort of 2088 children and adolescents, factors associated with increases in nonadherence included increasing age in years, female gender, detectable viral load, recent stressful life events, grade retention, and a diagnosis of depression or anxiety. These findings were similar to those of Murphy and colleagues,^[49] whose cohort were adolescents who were not congenitally infected.

Disclosure

The issues related to the disclosure of a child's or adolescent's HIV status are complex, and as a result, many caregivers and medical care providers are ambivalent about disclosing to children. This ambivalence is fueled by very realistic concerns about the stigma associated with HIV disease and the potential consequences of disclosure on the child and family. This is especially true given that disclosure of a child's HIV status may reveal parental HIV status as well, thus affecting the whole family.

The American Academy of Pediatrics has endorsed the disclosure of HIV to older children and adolescents and has developed guidelines to help families and clinicians cope with this difficult issue.^[51] Studies examining the impact of disclosure have been conflicting. Some studies report higher esteem, promotion of trust, improved adherence, and better health and well being.^[52] Other studies suggest that learning of one's HIV status may increase distress and contribute to the development of depression, anxiety, and behavioral problems.^[53] Disclosure optimally should occur in a planned and structured setting with parents or other caregivers and health care providers. The information should be provided in a developmentally, socioculturally, sensitive manner. It is also important that parents and providers be prepared for the potential postdisclosure reactions, which may be immediate or delayed and can range from no apparent emotion to severe distress. Most children and adolescents eventually go on to adjust to living with their illness.^[54]

It is clearly critical that adolescents be informed of their HIV status before they become sexually active, to maximize their own health behaviors and to decrease risk of transmission to others. Fear of rejection by peers if HIV status were known can prevent adolescents from disclosing, adhering to treatment recommendations, or from engaging in safe sex practices so as not to raise suspicions. It is crucial that adolescents understand their illness, when to disclose to supportive individuals, and how to elicit support when needed to cope with the demands of their illness.

Summary

Youths infected with HIV are living longer. While most are doing well, many struggle with the burden of their illness and the demands of living with this chronic condition. The focus of our efforts must be prevention of new HIV infections. The recognition and treatment of psychiatric conditions for adolescents who are HIV- and for those who are HIV+ are an important component of this effort.

Psychiatric conditions are increasingly recognized among HIV+ youths who were born with their HIV disease and among those who acquire their disease. Furthermore, psychiatric conditions have been identified as a risk factor for acquisition of HIV disease, transmission of HIV, and poor outcomes for those who are infected by decreasing the likelihood of adherence to treatment. Child psychiatrists and other mental health professionals can play important roles in the prevention of HIV infection for adolescents receiving psychiatric treatment by the identification and treatment of psychiatric conditions that may predispose adolescents to risk, evaluating the adolescents' sexual practices and risky behaviors that place them at risk, and intervening when appropriate.^[5]

When evaluating psychiatric disorders in HIV+ youth a comprehensive biopsychosocial assessment, using multiple informants involved in the child's or adolescent's care including caregivers, schools, and other agencies, should be used to understand the context in which the symptoms occur. A comprehensive assessment includes the identification of any stressors or events that might contribute to adjustment difficulties such as loss of family or friends, or changes in health status. An assessment of cognitive status, and adherence to antiretroviral treatments and safe health practices, should be included as well.

Although many child and adolescent psychiatrists express discomfort about asking or discussing sexual behaviors with high-risk teenagers who are HIV- or HIV+, clinicians can use direct questioning to ask adolescents about their sexual behaviors, the role of sexual relationships, the use of condoms, the context in which sexual activities occur, sexual attitudes and behaviors of their peer groups, and the quality of these relationships. A comprehensive assessment of sexual behavior and discussion with an adolescent in therapy provides a forum for open discussions about their sexual practices. Initiating these discussions with the adolescent within a therapeutic context demonstrates the importance of his or her concerns and the therapist's concerns about the adolescent's safety. Adolescents may use this process to gain awareness of unsafe sexual behaviors and to increase their motivation for change.^[55]

Although few treatment studies have focused specifically on treatments for psychiatric conditions among medically ill children and adolescents, and even fewer have focused on HIV+ children and adolescents, the few studies available suggest that interventions currently used for non-HIV+ children and adolescents may be effective. Special considerations and attention must be given to the side effect profiles of psychotropic medications, potential for interactions with other medications, and ease of administration for youths who may already be using antiretroviral therapies.

HIV remains a significant health risk for adolescents, and psychiatric illness may predispose adolescents to risk, perpetuate the burden of illness for those infected, and increase the risk for further transmission. Psychiatrists can play an important role in curbing this epidemic by identification and treatment of adolescents at risk, as well as improving the quality of life for those already struggling with this illness.

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