HIV in Children and Adolescents

Author(s): Kaile Eison, DO and Heakyung Kim, MD

Originally published:01/30/2014

Last updated:05/29/2018

1. DISEASE/DISORDER:

Definition

The reputation of Human immunodeficiency virus (HIV) infection precedes it. Its tumultuous history since its inception in the 1980s has made it one of the most infamous diseases in history. It is now known that HIV attacks CD4 T lymphocytes, leaving the patient vulnerable to life-threatening infections and malignancies. The advanced stage is a potentially fatal condition, acquired immunodeficiency syndrome (AIDS). Previously affecting primarily homosexual men (MSM) and IV drug users, HIV now affects individuals of all genders and ages. This article will focus in particular on those under the age of 21. HIV has been shown to be associated with lower quality of life (QOL) in children. This is for a multitude of reasons including impairments in functional status, health perceptions, physical resilience, and social roles, as well as language, cognition, and social development.

Etiology

HIV is transmitted by contact with infected blood/bodily fluids through unprotected sexual intercourse, from mother to child during birth or breastfeeding, unsafe medical injections/blood transfusions, or shared drug needles. Contracting other sexually transmitted diseases may increase susceptibility to HIV. Infection risk increases with the number of sexual encounters.

Epidemiology including risk factors and primary prevention

According to UNAIDS, there were approximately 36.7 million people living with HIV in the world by the end of 2016. 1.8 million of them were new infections. Since the start of the epidemic in the 1980s, still approximately half of those ever diagnosed have died from the disease. Of the 36.7 million still living with HIV, 2.1 million are under the age of 15. Only 43% of infected children are thought to have access to treatment, which, while an improvement from 21% in 2012, still means that over half of all infected children are not being treated. Fortunately, even with that statistic, the number of new pediatric HIV infections has declined 70% since 2010, due primarily to education and maternal accessibility to treatment, which is around 76%. The risk of maternal-child transmission can be lowered to 5% or less with proper treatment during pregnancy, delivery, or breastfeeding. However, that being said, there are still an estimated 150,000 new cases of pediatric HIV each year and around 400 new cases daily. Part of the reason for this is that only around 50% of infants exposed to HIV are being tested in high burden countries. Less data specifically targeting adolescents exists and is often combined with that of adults, but it is known that the overall majority of cases of infected adolescents are congenital. However, most new cases diagnosed in adolescents are a result of high risk sexual intercourse, prompting the American Academy of Pediatrics to recommend routine screening in higher prevalence areas. The age of sexual debut has been noted to be rising, however UNICEF estimates that 30-50% of females will give birth to their first child by 19. Additionally, rates of transactional intercourse, particularly between older men and adolescent women in developing countries, still remain high with an overall lower rate of condom use and higher rate of transmission from an older individual more likely to be living with HIV to the younger person. Within the United States, 75% of new infections in individuals between the ages of 13-24 have been MSM. While rates of transmission via blood transfusions or unsafe medical injections has decreased, the incidence of infection through intravenous drug use or injection of other substance remains an issue, particularly in certain populations, such as ethnic-minority transgender women, a population in which prostitution often at a young age remains prevalent.

Patho-anatomy/physiology

HIV is a retrovirus that uses reverse transcriptase to convert ribonucleic acid into deoxyribonucleic acid. It then replicates using the cell’s own machinery. It is part of the lentiviruses subgroup and has a prolonged period between initial infection and symptom onset, increasing the risk of unknowing transmission.

With time and lack of intervention, HIV may impact nearly every organ system in the body. For example, HIV impacts the both the central nervous system in part by weakening immune functioning and the peripheral nervous system, often causing debilitating neuropathy. Patients with poorly controlled HIV are at high risk for CNS infections such as toxoplasmosis, which can cause weakness, speech deficits, and altered mental status depending on the locations of the lesions. They are also at higher risk for certain malignancies, such as CNS lymphoma, which comes with its own neurologic, among other physiologic, deficits. Distal sensory polyneuropathy can also be caused by HIV, although the etiological mechanism is unclear. With disease progression, the likelihood of developing neurologic deficits increases. Particularly in children with congenital HIV, lower CD4 counts represent a higher risk for impairments in academic achievement, visual-spatial orientation, spelling, reading, and comprehension.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

HIV is a chronic infection that progresses in four stages: acute, asymptomatic, symptomatic, and AIDS. In the majority of individuals, HIV will progress to AIDS greater than 10 years, if left untreated. Mortality depends on many factors, including access to and compliance with treatment, opportunistic infection treatment, and nutritional status. In industrialized countries, HIV-infected children are increasingly likely to survive well into adolescence and adulthood, a transition which is now changing the face of treatment, both of the virus and from a rehabilitation perspective

Specific secondary or associated conditions and complications

1.Immunosuppression: primary complication that leads to opportunistic infections:

  • Candidiasis causing thrush is the most common OI, even at relatively high CD4 counts, though it does not frequently cause severe impairments unless extensive or causing esophagitis.
  • Pneumocystis jiroveci pneumonia remains a common OI, seen primarily with CD4 counts less than 200. Trimethoprim-sulfamethoxazole prophylaxis is recommended for HIV-exposed infants starting at age 4-6 weeks until a year old unless HIV can be definitively ruled out with virologic testing.

Worldwide, tuberculosis (TB) is the most common co-infection and leading direct cause of death.5

  1. Cardiovascular: adiposity, decreased lean body mass, hyperlipidemia, and insulin resistance are common, in part from the virus itself, with contributions from medication side effects.
  2. Osteopenia/osteoporosis.
  3. Direct damage to the peripheral nerves both by the virus itself and as a result of certain ARVs can cause severe, debilitating neuropathy.
  4. HIV encephalopathy leads to impaired brain growth, developmental delays/regressions, and motor deficits. HIV-infected children with structural brain anomalies demonstrated on computed tomography may be at risk for visual-motor and visual-spatial processing deficits.

2. ESSENTIALS OF ASSESSMENT

History

In younger children, much of the history may come from the child’s parent or caregiver. However, it is also important to assess the child’s understanding of his or her disease, as this will require life-long attendance. A child’s emotional and social well-being should also be assessed, which may need to be done without a parent in the room, especially since some studies have shown a higher rate of abuse in children living with HIV in certain populations. In older, sexually active children, understanding of sexual health, risky behavior, and routes of transmission should be discussed. Providers should also assess for severity and frequency of common childhood illnesses, such as otitis media or pneumonia, as these may be more frequent or severe than in a non-infected child, as are recurrent fungal or viral infections. Developmental delay (gross/fine motor, language, cognition, and social development) should be explored. Because these delays directly correlates with immune impairment, CD4 counts should be closely monitored and consistency with ARV should be evaluated. Inquiry should be made regarding memory, behavioral problems, and school failure.

Physical examination

Even in a rehabilitation setting, it is important to perform a comprehensive physical exam for children with a history of a systemic disease such as HIV. It is always important to monitor for signs of disease progression or evidence of opportunistic infections, such as lymphadenopathy (particularly epitrochlear), mucocutaneous sores or evidence of oral plaques such as in hairy oral leukoplakia or thrush, adventitious breath sounds suggestive of pneumonia, or hypo or hyperpigmented lesions on the skin as may be seen with fungal infections or Kaposi’s sarcoma. Additionally, about 25% of children with HIV develop an erythematous, papular rash as a result of HIV dermatitis. In children, it is also especially important to assess for signs of failure to thrive (weight for age below 5th percentile or weight deceleration crossing two major percentile lines on a growth chart). Poor nutritional status, common in many developing countries as well as in parts of the US, can increase the side effects of ARV and has been shown to portend poor outcomes and increased risk of opportunistic infections. Along with nutritional status, strength and endurance testing should also be evaluated. Visual motor and visual-spatial testing should be performed both for children with congenital HIV who may have deficits in visual or ocular development and in those who acquired HIV later on, since visual impairment may be seen as a result of infections (CMV, toxoplasmosis, HSV, VZV) or can be cerebral in nature. Children with HIV have been noted to have an increased risk of delays in gross and fine motor development, cognition, and social development. In older children, characteristic neurodevelopmental impairments include impaired motor and cognitive function, poor school performance, language impairments, shortened memory span, and impaired perception. HIV infected infants have been shown to score significantly lower scores on mental and motor subscales of the Bayley Scales of Infant Development.

It is important to note that many of these findings may be multifactorial in nature, not the least of which is environment and social support, which will be discussed later.

Functional assessment

Screening tests for developmental delay (e.g., Bayley Scales of Infant and Toddler Development) can be used. More specific tests (e.g., Wechsler Intelligence Scale for Children) can be performed as needed to assess for more subtle sequelae of the disease (memory, visual-spatial skills). The Infant Gross Motor Screening Test was developed specifically for HIV-infected infants between the ages of 6 and 18 months because motor function appears more severely affected than other developmental areas in this population. Manual muscle testing for strength deficits and a walk/run test for endurance issues should be considered.

Laboratory studies

HIV screening should be included in routine prenatal testing and repeated in the third trimester.

All newborns perinatally exposed to HIV should be treated with ARVs, preferably within the first 6-12 hours post-partum. The dosing and selection of ARV is multifactorial and is not within the scope of this article. For newborns with in-utero exposure, a CBC and an HIV DNA or RNA polymerase chain reaction test (as opposed to an antibody test) should be done at birth and repeated at 2 to 3 weeks, 1 to 2 months, and 4 to 6 months. Universal screening should be part of routine clinical care for patients starting at 13 years of age and repeated on a regular basis for at-risk adolescents.10

CD4 percentage, CD4 cell count, and plasma HIV ribonucleic acid should be measured at the time of diagnosis and repeated at least every 3 to 4 months to assess for disease progression.

Supplemental assessment tools

Consideration should be given to neuropsychologic testing in HIV-positive children given an increased risk of neurodevelopmental deficits.

Early predictions of outcomes

Analysis of HIV-infected children showed a strong correlation between low activated CD8+ T lymphocytes in the first 2 months of life and good immunologic prognosis.

There is a significant favorable association between low immune activation in peripheral T cells at age 1 to 2 months and subsequent psychomotor and mental development in HIV-infected children.

Environmental

The quality of the home environment (prenatal drug exposure, poverty, and violence/abuse) should be assessed because this is associated with the intelligence quotient and may influence adherence to treatment plans.

Inquiry should be made regarding smoking in the house because HIV-infected patients are particularly vulnerable to respiratory problems, eye infections, and other issues associated with indoor air pollution.

Social role and social support system

Although societal views on HIV have changed tremendously over the years, a great deal of stigma and prejudice surrounding a seropositive status remains. It is essential to acknowledge this, especially when working with adolescents, as this may have a profound impact on their social and emotional well-being.

Inquiry should be made regarding the family situation, including determination of the child’s primary caregiver. Parents should be assessed for stressors, such as chronic illness related to their own disease, low education/income, and minimal resources, which may increase the child’s susceptibility to poor development.

Professional Issues

Physicians should report all instances of prenatal exposure to antiretroviral drugs to the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.apregistry.com).

Physician reporting of HIV remains a somewhat controversial topic. Health care providers in the US are required to report an HIV diagnosis to public health authorities. Providers are also permitted to inform at-risk partners of those with HIV. It is state dependent whether the provided must inform the patient first that he or she will be disclosing his or her status to another individual. However, patients should be assured that neither their name nor their physicians’ names are disclosed during partner notification.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

There is no question that exercise is beneficial for patients with HIV. Since both the disease itself ARV therapy can come along with side effects such as fatigue, muscle weakness, and depression patients often look towards non-pharmacological treatment options.  There are no clinical evidence-based guidelines on the rehabilitation of children with HIV/AIDS. However, progressive resistance exercise training of HIV-infected adolescents has been shown to lead to an improvement in muscle strength/body composition and a decrease in visceral/subcutaneous adipose tissue.

At different disease stages

HIV/AIDS is a chronic disease.

  1. In the first 3 stages, rehabilitation may consist of strengthening/endurance exercises, ensuring proper nutrition, and addressing developmental deficits. There is some evidence that massage therapy may improve the immune functioning of HIV-infected children.
  2. Once the patient has developed AIDS, care may center around addressing deconditioning, as well as the medical management of any complications or opportunistic infections.
  3. Advanced stages–palliative and home-based care:
    • Pain management.
    • Coordination of habilitative/rehabilitative care.

In cases of mother-to-child transmission, a treatment regimen, such as the following, could be considered:

  1. 0 to 3 years: monitoring and treatment of developmental delays, particularly gross motor function, with early referral to physical/occupational/speech therapies.
  2. School age: strengthening/endurance exercises with emphasis on a consistent home exercise program.
  3. Adolescence: progressive resistance exercise training, ongoing education regarding the disease, importance of treatment adherence, and proper nutrition.
  4. Adulthood: exercises to address deconditioning and palliative care when appropriate.

Although medication regimens for HIV have become significantly less complicated over the years (previously requiring up to 12 ARV pills a day, not including prophylactic or other medications) it is important to note the burden taking any medication, let alone one required daily and life long, may have on a child or teenager. There is the mechanical difficulty of children swallowing pills, but there is also an emotional component. Finding ways to convey the significance and import in a way that a child can understand can be a challenge, as can explaining the consequences of noncompliance.

Interestingly, studies have shown that HIV positive children in the US are not more likely than children without HIV to have mood problems or psychiatric symptoms, however they are more likely to receive medication or behavioral treatment for it than their counterparts. It is important to consider this when assessing what may already be a complicated medication regimen.

Coordination of care

An interdisciplinary team approach to any HIV positive patient is essential. Management of the virus itself should be followed by a specialist in pediatric HIV and should be transitioned to a physician specializing in adult HIV as the child ages. Furthermore, given the increased rate of infections and complications often faced by seropositive individuals, follow up with other specialists such as ophthalmology, dental, psychiatry, and OBGYN may be needed. Physiatric involvement is an underutilized but needed component in the care of HIV positive individuals of any age. As HIV becomes a disease with which people are surviving longer, adults are encountering impairments, particularly neurological and musculoskeletal, related to aging not previously encountered. Starting rehabilitation early on in the course is important for the functional longevity of this population.

Patient & family education

In addition to ARVs, more inclusive pre/postnatal care (screening, prophylactic treatment) may decrease mother-to-child transmission.

Caregivers should be extensively educated about regimen adherence. Barriers to adherence should be anticipated and addressed. Additionally, the benefits of exercise and the importance of staying active should be stressed.

Patients should be questioned regarding coping with their illness and referred to support groups/psychological services as needed.

Emerging/unique Interventions

Quality of life (QOL) measures, such as those described in the Pediatric AIDS Clinical Trials Group, assess a child’s physical, psychologic, and social functioning within the context of their development (impairments in functional status, health perceptions, physical resilience/functioning, and social/role functioning), and may provide more complete information regarding the overall impact of the treatment regimen.

WeeFIM scores (although not specific for HIV-infected children) measure the impact of developmental strengths/difficulties with independence at home, in school, and in the community. It remains a valid measure for tracking disability in children

It is important to note that efforts are being made in some high-burden countries to target adolescents in particular through such changes as opening age-specific clinics, offering night-time HIV testing for out of school adolescents or appointments during school holidays for those still in school, and establishing adolescent peer support groups. Adolescence is a time that often occurs in conjunction with rebellious, risky behaviors, a need for both acceptance and autonomy, and the development of decisional capacity. As a result, it is essential that these interventions continue to help access this vulnerable population.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  1. Antiretroviral prophylaxis is recommended during pregnancy/delivery/breastfeeding. Caesarean sections reduce transmission risk during delivery.
  2. Lower CD4 counts represent a higher risk for developmental delay.
  3. Clinical assessment of nutrition is important because malnutrition increases the risks of side effects of ARVs and accelerates the development of immune deficiency/opportunistic infections.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

An interesting dynamic shift is occurring in regards to HIV transmission. As HIV becomes less of a terminal diagnosis and more a chronic, manageable illness from which sexual transmission can even be prevented with the advent of pre-exposure prophylaxis medications (PreP), the ethical dilemma of whether or not to disclose an HIV positive status becomes less clear. This current generation of adolescents and young adults is the first generation to grow up not having been alive during the height of the AIDS crisis. The consequences of transmission and failure to treat are less tangible now than they have ever been.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

A recent study demonstrated that adolescents with perinatally acquired HIV showed some deficits in muscle power when compared to age and sex specific controls. It was a small study (n=35) and requires further investigation.

A 2012 study showed that HIV-affected preadolescents have impaired anaerobic capacity, which may limit their activities of daily living. Progressive resistance exercise training may address this by improving muscle strength and body composition. Follow ups on this study have not yet been published.

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Original Version of the Topic

Marykatharine Nutini, DO Dennis Nutini, MD. HIV in Children and Adolescents. Original Publication Date: 01/30/2014.

Author Disclosures

Kaile Eison, DO
Nothing to Disclose

Heakyung Kim, MD
Nothing to Disclose

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