Human immunodeficiency virus-1 (HIV), a lentivirus that attacks the body’s immune system, can over time progress to Acquired Immunodeficiency Syndrome (AIDS), a condition in which progressive immune system dysfunction and failure leaves individuals vulnerable to deadly opportunistic infections and cancers. HIV’s tumultuous history since its discovery in the 1980s has made it one of the most infamous diseases in history. In the four decades since the start of the HIV epidemic, over 36 million people have been infected and died from HIV and HIV-related complications, a stark reminder of the overwhelming devastation caused by the virus.1 Fortunately, advances in prevention and treatment, such as the development of antiretroviral therapies (ART), have helped transform HIV from a life-threatening illness to a treatable albeit incurable chronic illness. That being said, the burden of HIV remains high globally, and it is now known to affect individuals of all genders and ages. This article will focus in particular on children and adolescents.
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. Recent literature has begun to focus on frailty in people living with HIV and the concepts of accelerated versus accentuated aging (reference). While this has not yet been reflected in the pediatric literature, it is clear that people living with HIV are beginning to show signs of aging earlier and faster, a phenomenon which may become relevant both in the symptomatology of the young population currently aging with the virus, as well as in the prevention of comorbidities in the future.
HIV is transmitted through unprotected sexual intercourse, exposure to blood or blood products, or from mother to child during birth or postpartum through breastfeeding.
The majority of children living with HIV (CWHIV) are infected perinatally, which include infection in utero, intrapartum, and postpartum period. In absence of treatment, the risk of transmission from an HIV+ mother to the infant is between 15-45% in the perinatal period. The development and increased availability of ART has dramatically decreased mother-to-child transmission as well as infant and child mortality. However, mother to child transmission remains a significant contributor to the global pandemic, accounting for 9% of new infections each year.2
The number of adolescents with HIV (AWHIV) is increasing due to survival of children infected perinatally. The AWHIV population is thus a complex, heterogeneous population of CWHIV infected perinatally aging up to adolescence and those horizontally infected with HIV during adolescence. Perinatally infected adolescents often have more advanced HIV disease and comorbidities resulting from lifelong infection and/or treatment. There are significant sex differences in etiology amongst the AWHIV population with 57% of older male adolescents (aged 15-19) infected perinatally compared to 35% of older female adolescents.3 These sex differences are particularly prominent in low- and middle-income countries in Eastern and Southern Africa that bear most of the current brunt of the HIV epidemic.
Epidemiology including risk factors and primary prevention
According to UNAIDS, there were approximately 37.7 million people living with HIV in 2020, with1.5 million new infections. An estimated 1.7 million are under the age of 15. There are an additional estimated 1.3 million people living with HIV between the ages of 15-19, meaning CWHIV and AWHIV combined total close to 10% of the total HIV population.
The vast majority of people living with HIV live in Sub-Saharan Africa. This includes AWHIV and CWHIV, with estimated 85-90% of these populations living in Sub-Saharan Africa. In 2016, 71% of the estimated 2.1 million AWHIV lived in just 10 high-burden countries, 9 of which are in Sub-Saharan Africa.4 AWHIV are the only age group in which HIV mortality is increasing, a frustrating trend in the time of global scaling up of access to ART.5 HIV remains the 8th leading cause of death for adolescents globally and 4th for adolescents in low and middle income countries (LMIC) in Africa.6 As noted above, the risk of maternal to child transmission has declined significantly in the era of ART, however there were still 150,000 new infections amongst children in 2019. While the access to pediatric ART has increased dramatically, coverage in children lags behind that in adults with only 54% of CWHIV globally accessing treatment in 2018 compared to 62% of adults.4
In the United States, the increased availability of interventions like ART and pre- and post-exposure prophylaxis (PrEP and PEP, respectively) have dramatically reduced the transmission and incidence of HIV. However, there were more than 37,000 new infections in 2018 and 57% of these diagnoses were amongst people aged 13-24 years, which points to the unique challenges of prevention and treatment in this age group. The burden of HIV in the United States is increasingly concentrated amongst racial, ethnic, sexual and gender minorities, and in the geographic South. For example, Black people accounted for 43% of new HIV diagnoses in the United States in 2018 despite making up only 13% of the population. Data from men who have sex with men (MSM) illustrate the geographical variation in disparities: rate ratios of Black MSM to White MSM range from 2·4 to 10·1 by state, and three of the six highest state-specific rate ratios are in the geographic South.7 Social determinants of health, including poverty, low education level, inequitable access to health care, and income inequality, disproportionately impact minority and disadvantaged populations, reinforcing these disparities.
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, more common in low- and middle- income countries (LMIC), 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 have 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.
HIV is a retrovirus that uses reverse transcriptase to convert ribonucleic acid into deoxyribonucleic acid and integrate itself into the host cell genome. It requires expression of CD4+ receptors and specific cell-surface coreceptors (i.e. CCR 5) for viral entry and cell infection. HIV is known to infect CD4+ cells, monocytes, macrophages, and glial cells. It often has a prolonged period between initial infection and symptom onset, increasing the risk of unknowing transmission.
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 in greater than 10 years, if left untreated. Prior to the introduction of ART, approximately 20% of CWHIV would develop AIDS or die by 2 years of age, and 60-70% would develop AIDS symptoms or conditions by age 7-8.8 Mortality depends on many factors, including access to and compliance with treatment, opportunistic infection treatment, and nutritional status. In the era of ART, and particularly in high-income countries, HIV-infected children are now 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. Despite the successes, much work remains as CWHIV still face significantly higher odds of morbidity and mortality compared to their uninfected peers.9
Specific secondary or associated conditions and complications
Central Nervous System (CNS)
With time and lack of intervention, HIV may develop into AIDS and impact nearly every organ system in the body. CNS involvement in advanced AIDS is perhaps one of the most well-known complications. While becoming less common in high-income countries, neurological opportunistic infections, particularly cryptococcal and tubercular meningitis, toxoplasma encephalitis, progressive multifocal leukoencephalopathy, and CNS lymphoma continue to pose a significant burden globally, especially as access and adherence to ART remain major issues in LMIC.
Fortunately, most of the infectious causes of CNS complications are almost entirely preventable with consistent ARV use and maintenance of a CD4 count>200. Additionally, when compared to an age and sex matched cohort, people living with HIV have a rate of stroke that is nearly triple. And while traditional risk factors do exist, both immunosuppression with lower CD4 count and uncontrolled HIV viremia appear to be associated with greater stroke risk. The reason for this is likely multifactorial, including smoking, high blood pressure, poor diet, drug use, however there is thought to be a significant component related to the chronic inflammation in the setting of HIV, immune dysregulation and side effects of HAART. This is seen most acutely in regions of sub-Saharan Africa where HIV is endemic and where HIV is the leading risk factor for stroke in young populations. In a 2007 study from South Africa, the median age of stroke was 33.4 years and 39.8 years in a similar 2012 study from Malawi (reference).
CWHIV have increased risk of cerebrovascular disease from multiple etiologies. Previously attributed to sequelae of opportunistic infections and malignancies, the incidence of CVD in HIV has remained stable despite the declining incidence of opportunistic infections. and neoplasms among CWHIV. It is estimated that 1-2% of CWHIV develop stroke clinically, which is likely an underestimate due to the limited availability of neuroimaging globally. HIV-associated cerebral vasculopathy is a known complication of HIV, affecting predominantly medium-sized cerebral vessels with radiological evidence of vessel stenosis, occlusion, or aneurysmal dilatation and excluding vasculitis secondary to opportunistic infection or malignancy.10 It is hypothesized that HIV can directly infect the vessel wall or the vasculopathy is secondary to the systemic inflammation involved with HIV. The functional impairments related to CNS pathology is well-known in the world of rehabilitation medicine, and these must be addressed given the disproportionately young population affected.
In the pre-ART era, HIV encephalopathy, characterized by predominantly motor illness with hyperspasticity, hyperreflexia, rigidity, increased muscle tone as well as severe neurodevelopmental delay were common in CWHIV. The incidence of these conditions has declined in the era of ART, by more than 10-fold in regards to HIV encephalopathy according to Pediatric AIDS Clinical Trials Group.9
Even in the era of ART, CWHIV and AWHIV can still experience subtle to severe neurocognitive effects, including general cognitive, language and speech, gross motor, fine motor and other psychosocial deficits. It has been shown that HIV-infected children treated with HAART have lower neurocognitive scores than uninfected peers. A recent meta-analysis demonstrated an association between HIV infection in children and adolescents and neurocognitive impairment, mainly in the domains of working memory, executive function and processing. The mechanism of this is mostly unknown but possibilities include nerve injury prior to initiation of ART, neuronal injury from neurotoxic viral proteins and inflammation, and poor CNS penetrance/neurotoxic effects of ART. Early initiation of ART and viral suppression has been shown to improve neurocognitive outcomes in infants with HIV.
In addition to the central nervous system, both the virus itself and certain antiretrovirals can affect the peripheral nervous system, causing damage not only to the perineural schwann cells, but also to the axon themselves, through mitochondrial degradation. This can lead to debilitating polyneuropathy at a young age, which can pose significant difficulties with mobility, as well as impacting individuals’ quality of life.
Opportunistic and Co-Infections
In the era of ART, the incidence of many devastating opportunistic infections and malignancies has declined. Amongst children, oral candidiasis remains the most common opportunistic infection, which may have a significant impact on infants’ or children’s feeding practices. The presence of coinfections such as tuberculosis and disseminated atypical mycobacterial infections are also frequently seen, particularly in older children. Concurrent CMV infection has been shown to accelerate the disease course in infants.8
CWHIV are at risk for a number of musculoskeletal complications, some of which are caused by HIV infection itself and others by conditions that lead to impaired growth and development. CWHIV are at risk for osteoporosis due to toxic effects from the virus affecting bone mineral density-related growth factors as well as from ART exposure, particularly with Tenofovir disoproxil fumarate.9 The risks of bone disorders are magnified in children compared to adults due to the high rate of bone mass increase during childhood and acceleration during adolescence. Globally, the age at ART initiation appears to be an important predictor of bone density. A cross sectional analysis of CWHIV in ZImbabwe aged 6-16 on ART showed that CWHIV starting ART after the age of 8 years had, on average, at least 1 standard deviation lower size-adjusted lumbar spine bone density.6 An important confounding variable is the relationship between bone strength and muscle strength. Poor health from HIV infection may impact physical activity levels and impair muscle strength and skeletal loading, thus negatively impacting bone development
CWHIV on ART are at increased risk for metabolic disorders including lipodystrophy, lipoatrophy, and lipohypertrophy. Studies have reported a wide prevalence of these complications in CWHIV and AWHIV, with one study in Thailand reporting a prevalence of lipodystrophy of 65% in CWHIV.9 Older ART drugs including AZT are most strongly associated with these conditions. Risk factors include a longer duration on ART, older age and more severe disease. Body fat changes may have an unintended secondary negative effect on adherence to ART in CWHIV and AWHIV due to their impact on body image, affecting two age groups where social pressures and stigma can play major roles in development.
CWHIV are also at higher risk of developing insulin resistance and subsequent diabetes mellitus. A 2011 study amongst a large cohort of CWHIV in the United States found insulin resistance in 15% of the cohort, which was strongly associated with low CD4 count and exposure to protease inhibitors.11 It is hypothesized that the systemic inflammation involved with HIV infection drives the release of pro inflammatory cytokines that can alter the hypothalamus-pituitary-axis affecting glucocorticoid production. These metabolic changes can predispose CWHIV and AWHIV to early cardiovascular disease.
There is a wide range of prevalence estimates for cardiac abnormalities in CWHIV with a wide spectrum of abnormalities reported. Current evidence suggests that CWHIV may be at increased cardiac risk due to viral mechanisms, exposure to ART for treatment or in utero for PMTCT or some combination. HIV infection in children has been shown to be associated with thicker carotid intima media, a measure of subclinical atherosclerosis, and that a low CD4+ T-cell nadir is related to an increased carotid intima thickness. Lower CD-4 count and older age of ART initiation are independently associated with increased risk of cardiomyopathy. There is evidence supporting cardioprotective effects from ART, especially early in life. Over 3000 CWHIV followed in the US-based Pediatric AIDS Clinical Trials Group were followed from 1993-2007 and showed the use of ART dramatically reduced incidence of cardiomyopathy.12
CWHIV are also at risk for developing chronic lung disease. A 2018 systematic review of lung function in CWHIV showed HIV-infected participants had increased irreversible lower airway expiratory obstruction and reduced functional aerobic impairment on exercise, compared to HIV-uninfected participants. Furthermore, pulmonary function tests in children established on antiretroviral therapy did not show aerobic impairment and had less severe airway obstruction.13 Several studies, mainly from low income settings, have reported a high burden of chronic respiratory symptoms among CWHIV on ART including cough, breathlessness and hypoxia however these setting often have a higher prevalence of social and environmental risk factors (air pollution, growth failure, malnutrition, delayed ART initiation).
Several studies report a high prevalence of mental health disorders amongst CWHIV and AWHIV. One large Ugandan study with 1300 CWHIV and AWHIV reported a prevalence of 17% of any psychiatric disorder and a 10% prevalence of any behavioral disorder, most commonly Attention deficit hyperactivity disorder (ADHD).14 A review of 8 studies on the prevalence of psychiatric disorders amongst CWHIV and AWHIV reported higher than expected rates of ADHD (29%), Depression (25%), and Anxiety (24%).15 However in larger and more well designed trials with established control groups, the evidence has suggested that CWHIV were no more likely to have psychiatric symptoms than age matched controls however were significantly more likely to be diagnosed and have received treatment for a psychiatric disorder. Children and adolescents living with HIV face recurrent and cumulative psychosocial stressors including stigma, discrimination, care for siblings, and unstable guardianship that differ from other childhood chronic illness that may leave them psychologically vulnerable and ill prepared for coping with challenges.
Growth and Development
Loss of developmental milestones or failure to achieve adequate developmental stages have long been recognized as an AIDS-defining condition. Perinatal HIV infection does not show any overt clinical manifestations of developmental delay at birth, often manifesting in childhood. A key predictor of altered neurodevelopment is disease severity, generally with stronger associations than immunologic or viral measures. Significantly lower functioning is reported in those with WHO Class C events or AIDS diagnosis.16 However, the degree to which developmental impairments are attributed to HIV versus other developmental, environmental, and socioeconomic risk factors varies.
Often accompanying developmental delay is growth failure. HIV infection is associated with impaired linear growth (stunting), growth failure, and pubertal delay. Throughout childhood, CWHIV tend to have shorter stature, lower body weight and delayed entrance into puberty compared to uninfected peers, even in the absence of overt AIDS or wasting. The specific pathways which result in impaired growth are multifactorial, including malnutrition, chronic inflammation, opportunistic infections, gastrointestinal illnesses, and endocrine abnormalities. Lower CD4 count and higher viral load have been shown to be associated with delayed pubertal onset, and longer duration of ART is associated with more normal pubertal onset, which suggests ART can lead to more normal growth patterns.9 However, there are limited data from Sub-Saharan Africa and other resource limited settings, where children are more likey to be malnourished, suffer from diseases such as persistent diarrhea that are associated with poor growth, and face a number of social and environmental factors that may also negatively impact growth and development.
Hearing, Speech, and Language
HIV infection is known to have adverse effects on hearing, language and speech development. HIV is most associated with conductive and/or sensorineural hearing loss and expressive language deficits. A cross sectional analysis of 380 CWHIV in Malawi aged 4-14 found 23% prevalence of hearing loss with the majority of cases showing conductive hearing loss due to increased susceptibility to infections such as otitis externa, chronic otitis media, and cholesteatoma.17 An important rehabilitation consideration is the ability of CWHIV to wear hearing aids due to inflammation, pain, and drainage in the external auditory meatus. Concurrent CMV infection, the most common cause of sensorineural hearing loss in children, may exacerbate hearing deficits and loss.
Research has highlighted a common trend of speech and language disorders in CWHIV. One study of preschool children in the United States and Puerto Rico estimated the prevalence of language impairment to be 15%, with a greatly reduced risk for those exposed to ART in utero.18 A longitudinal evaluation of language impairment in CWHIV found that ⅓ of infants born to HIV+ mothers had language impairment that persisted into adolescence.19
Despite the availability of ART, the life expectancy of HIV-infected individuals in Western countries is shortened by an average of 10 years. The aging process is seemingly accelerated in individuals with HIV, a trend that impacts both adults and children living with HIV. CWHIV have been shown to have premature immunosenescence of B and T cells, which is mediated through immune system activation and chronic inflammation, both of which are hallmarks of HIV infection. Another reported feature of premature aging includes cellular replicative senescence linked to acceleration of telomere shortening. Peripheral blood leukocytes analyzed from perinatally infected children have shown typical features of aging immune systems (i.e increased NK, decreased CD19) with high levels of cell markers associated with apoptosis.20 There may be an effect of HIV on B cells as well which can impair immune response to vaccines, exposing CWHIV to otherwise preventable illnesses.
Essentials of Assessment
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 CWHIV in certain populations. In potentially sexually active adolescents, 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 correlate with immune impairment, CD4 counts should be closely monitored and consistency with ARV should be evaluated. It should be noted, however, that there may be a negative correlation between CD4 count and age in children with vertically-acquired HIV,23 so it is important to assess for other signs of decompensation, such as an elevated viral load. Inquiry should be made regarding memory, behavioral issues, and school performance.
In adolescents, adherence to ART therapy represents a major challenge to HIV care that should be explored in the history. It is now known that AWHIV experience poor rates of retention in care and adherence to ART compared with adults. It is estimated that only 20% of the world’s AWHIV are on ART.5 In South Africa, AWHIV aged 15-24 have the lowest proportion of adherence to ART with only 10% virally suppressed.21 This issue is not restricted to LMIC. In the United States, approximately 50% of AWHIV remain undiagnosed, the highest of any age group. AWHIV are also the least likely to be linked to care within 1 month, retained in care, and virally suppressed.5 As with other issues surrounding HIV care, there are a plethora of factors that contribute to this issue including perceived and experienced stigma, fear of disclosure of HIV status to others, and concurrent mental health issues. Additional adherence challenges in infants and children include issues with palatability, swallowability, and dispensability of antiretroviral drugs.
Poor or incomplete adherence leads to the development of drug resistance mutations. Not surprisingly, drug resistance in CWHIV and AWHIV can lead to future challenges in treatment, especially in resource limited settings, given these individuals will likely require lifelong treatment. One study from the United Kingdom that analyzed 644 adolescents transitioning to adult care found that 82% had resistance to one drug class and 56% to two classes.22 Higher rates of drug resistance mutations found in those infected perinatally compared to horizontal infection, reflecting differences in duration of treatment and exposure to ART in order to develop resistant mutations.
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 parts of the world, including in parts of the United States. , 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 should be closely monitored for 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.
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.
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.
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 and response to treatment.
Early predictions of outcomes
In perinatally infected children, viral load at birth and the magnitude and duration of viremia are predictors of poor outcomes. Analysis of CWHIVn 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.
Growth parameters have been shown to be particularly useful clinical surrogates in assessing disease progression, especially in resource limited settings.
Poorer outcomes have been reported for AWHIV in general and for older youth in particular. Adherence to ART is the critical behavior underlying many of the long-term outcomes in CWHIV and AWHIV. As referenced above, many of the complications and negative sequelae associated with HIV infection can be prevented or at least managed with early initiation of ART.
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. Several scales exist to attempt to quantify level of stigma, most notably the HIV Stigma scale, but none of these have been validated in children or adolescents.
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.
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.
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 and treatment can cause 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 now a chronic disease.
- 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.
- Once the patient has developed AIDS, care may center around addressing deconditioning, as well as the medical management of any complications or opportunistic infections.
- 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:
- 0 to 3 years: monitoring and treatment of developmental delays, particularly gross motor function, with early referral to physical/occupational/speech therapies.
- School age: strengthening/endurance exercises with emphasis on a consistent home exercise program.
- Adolescence: progressive resistance exercise training, ongoing education regarding the disease, importance of treatment adherence, and proper nutrition.
- 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.
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. This transition period of adolescence while dealing with a chronic disease and sexually transmitted infection, is a time of great risk to being lost to follow up. 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.
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.
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
- Antiretroviral prophylaxis is recommended during pregnancy/delivery/breastfeeding. Caesarean sections reduce transmission risk during delivery.
- Lower CD4 counts represent a higher risk for developmental delay.
- 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.
Cutting Edge/ Emerging and Unique 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.
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.
There is an urgent need for evidence-based interventions in the adolescent care cascade including supporting retention in care and adherence with ART.
Historically, data on the HIV burden in transgender people have been sparse; much of the available data have focused on transfeminine populations with little attention to transmasculine or gender non-binary communities. Improvements in data collection methods and data quality are needed to gain a better understanding of the national HIV burden among transgender people for the development of effective prevention efforts and programs targeted to this population.
- UNAIDS Fact Sheet. Available at http://www.unaids.org/en/resources/fact-sheet. Accessed Feburary 24, 2022.
- Fabusoro OK, Mejia LA. Nutrition in HIV-Infected Infants and Children: Current Knowledge, Existing Challenges, and New Dietary Management Opportunities. Adv Nutr. 2021;12(4):1424-1437.
- UNAIDS. Ending AIDS: progress towards the 90-90-90 targets. Available from: https://www.unaids.org/en/resources/documents/2017/20170720_Global_AIDS_update_2017. Accessed March 1, 2022
- Frigati LJ, Ameyan W, Cotton MF, et al. Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy. Lancet Child Adolesc Health. 2020;4(9):688-698.
- Enane LA, Vreeman RC, Foster C. Retention and adherence: global challenges for the long-term care of adolescents and young adults living with HIV. Curr Opin HIV AIDS. 2018;13(3):212-219.
- Slogrove AL, Sohn AH. The global epidemiology of adolescents living with HIV: time for more granular data to improve adolescent health outcomes. Curr Opin HIV AIDS. 2018;13(3):170-178.
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Original Version of the Topic
Marykatharine Nutini, DO Dennis Nutini, MD. HIV in Children and Adolescents. 1/30/2014
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Kaile Eison, DO, Heakyung Kim, MD. HIV in Children and Adolescents. 5/29/2018
Kaile Eison, DO
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Daniel Childs, MD
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