Childhood AIDS

• 90% (1.8 million) of HIV positive children live in Sub-Saharan Africa.
• Less than 200 of the new infections in children in 2007 occurred in the whole of the West and Central European region.
• Access to anti-retroviral therapy has improved recently in low and middle income countries (3 million HIV positive individuals were treated in 2007) but children are significantly less likely than adults to receive them.
• Whilst the global epidemic has shown signs of stabilizing in the last few years, this seems to be occurring at unacceptably high levels in those countries that bear the brunt of the disease burden.

Children suffer not only from the direct effects of AIDS itself but from the fact that their primary caregivers are very likely also to be affected or to have died from the disease. In 2007, approximately 12 million children had been orphaned by HIV.¹ Care of children and adolescents with AIDS needs to be family-centred and to consider psychological and social aspects of the disease as well as medical. Children will have been disadvantaged economically as well as educationally by the effects of HIV and AIDS in most areas of the world.

The great majority of new paediatric infection occurs from mother to child and accounts for the bulk of 1,000 new paediatric infections daily globally, most of which occur in high prevalence zones.¹

Worldwide:

• Without intervention, between 25-40% of babies born to HIV infected mothers in the most severely affected countries are also infected.³ With appropriate interventions (antenatal detection of HIV positive status, antiretroviral treatment, caesarean section and avoidance of breast feeding), mother-to-child transmission rates can be reduced to less than 1%. Consequently, much emphasis has been placed on preventing mother-to-child transmission (PMTCT) of HIV.
• There has been improvement in the access of pregnant women with HIV to antiretrovirals during pregnancy and delivery from 9% in 2005 to 34% in 2007, although this has wide geographic variability.¹

In the UK:

• There is the universal offer and recommendation of HIV testing at antenatal booking and about 95% of HIV positive women are currently identified prior to delivery, enabling preventative strategies to be used. Late booking or testing after 28 weeks demands rapid or point of care testing, particularly if there is risk of preterm labour.
• Whilst vertical transmission rates have fallen, HIV prevalence and detection rates in pregnant women has continued to rise.
• There is a 0.09% prevalence of previously undiagnosed HIV infection in pregnant women in the UK, with the largest focus in London (where the rate is 0.21%).⁴ Most HIV positive mothers and many HIV positive children in the UK acquired their infection elsewhere, notably in Sub-Saharan Africa. UK prevalence rates of previously undiagnosed HIV infection amongst pregnant women born in this region are 2.4%.⁵
• Of UK resident children reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) as being HIV positive between 2003-6, 64% had been born abroad, compared to 24% during 1994-1996.⁶

Transmission

• Most new cases of paediatric AIDS are due to vertical transmission. Of the 2,000 children under 15 years diagnosed with HIV in the UK to date, over three-quarters have acquired infection from their mother and the rest largely from blood products in the early 1980s.
• The exact mechanism of vertical transmission is unknown but thought due to intrauterine exposure when maternal blood enters the fetal circulation, or more commonly during labour, particularly when there is prolonged rupture of membranes. Breastfeeding also increases the risk of infection but this has to be balanced against the need for safe nutrition.
  

  A negative maternal HIV test at booking does not preclude neonatal infection - maternal infection and seroconversion can occur at anytime during pregnancy and lactation. This is well documented in countries with a high prevalence of HIV and has been seen in the UK.7

• Complex obstetric events including late/non-booking, poor treatment adherence or premature delivery have resulted in occasional HIV transmission mother-to-child in the UK despite an antenatal diagnosis.⁷
• Sexual abuse of children and adolescent high risk activity (unprotected sexual intercourse, intravenous drug use, risky sexual practices etc.) can also contribute to infection. Worldwide, there are unknown numbers of children of all ages (particularly street children and children in conflict zones), who acquire AIDS as a result of rape, sex undertaken for money or infected needles.

• Failure to thrive
• Delayed developmental milestones
• Difficulty in walking
• Recurrent bacterial and viral infections
• Pyrexia of unknown origin
• Chronic diarrhoea
• Fitting
• Persistent oral candidiasis
• Recurrent pneumonia
• Lymphadenopathy
• Neoplasms (B-cell lymphoproliferative diseases)

• Multiple infections
• Congenital immunological disorders e.g. DiGeorge syndrome, chronic granulomatous disease
• Malnutrition

Consent for testing⁸

Testing a child for HIV has large implications for the family as most cases involve vertical transmission. It should never be done as an emergency or without the family's full counselling and their time to consider implications of a positive test result. Information given should be culturally appropriate and interpreters used as needed. See Consent To Treatment In Children.

• Those with parental responsibility or the courts can give consent for testing in children and young people without capacity. Ideally both parents should be involved but the mother's consent is particularly important given the likelihood of her HIV positive status.
• Children and young people should be involved as much as possible in decisions about their care, even when they are not able to make independent decisions.⁹
• Those under 16 years are able to consent for themselves if they show "Gillick'/Fraser competence".
• Conflict can sometimes arise between parental and medical desire for testing - benefits of testing should be clearly outlined as part of the counselling procedure.
• With 'looked-after' children, parental responsibility is often shared between parents and local authority. Where a child does not have capacity and is a ward of court, only the court can give consent for testing.
• Testing should only be done if it is in the best interest of the child. Routine testing prior to adoption or fostering is not acceptable and should only be done where medically indicated.

Confidentiality needs to be stressed at all times. Parents and children are distressed by the stigma of their disease and the prospect of any discrimination against them on the basis of it. As children become older, it is appropriate that they are involved in discussion and a growing understanding of their diagnosis.

Diagnostic tests¹⁰

Early diagnosis of HIV infection is crucial and ideally should occur rapidly postnatally where mothers are known to be HIV positive as this allows for prophylaxis against, early detection and treatment of opportunistic infection in neonates.

• Standard ELISA tests are unreliable for the first 18 months because of the transmission of maternal antibodies which persist for some time in the baby.
• PCR of viral DNA can be used for early detection in infants of HIV mothers and is usually performed at 0-2 days, 6 weeks and 3 months.

Second line, confirmatory tests include:

• HIV RNA PCR
• Baseline HIV resistance (+/- maternal HIV resistance)
• CD4 count
• HLA B5701

Additional tests

Additional tests are performed at diagnosis to assess concurrent infection and risk of different opportunistic infection and can include:

• Serology for Hepatitis A, B, C, EBV, CMV, HSV, mumps, measles, rubella, VDRL and toxoplasmosis
• Malaria film
• Mantoux test/TB cultures
• Baseline CXR
• Brain ultrasound/MRI (where neurological signs)

Monitoring

• CD4 counts
• Viral load
• Screening - audiology, dental, neurodevelopmental, ophthalmology, TB
• Additional tests in line with drug therapy protocols and clinical status

CDC paediatric HIV classification:¹¹

• Category N - asymptomatic
• Category A - mildly symptomatic. 2 or more of:
  • Lymphadenopathy
  • Hepatomegaly
  • Splenomegaly
  • Dermatitis
  • Parotitis
  • Recurrent/persistent URTI, sinusitis or otitis media
• Category B - moderately symptomatic with illnesses that result from HIV infection. These include:
  • Bacterial meningitis, pneumonia or sepsis (single episode)
  • Oropharyngeal thrush lasting longer than 2 months
  • Recurrent or chronic diarrhoea
  • Lymphoid interstitial pneumonia
  • Nephropathy
  • Fever lasting at least 1 month
  • Disseminated varicella
• Category C - severely symptomatic with an AIDS defining illness

Within these categories, a measure of immunological suppression (based on CD4 count related to age) is designated by a number (1=no suppression, 2=moderate suppression and 3=severe suppression). For example, A2 refers to a mildly symptomatic child with moderate suppression of CD4 count.

Prophylaxis of opportunistic infection

Standardly, HIV positive infants receive co-trimoxazole for the first year of life (regardless of CD4 count) against Pneumocystis jiroveci (carinii) pneumonia (PCP). Thereafter, its continued use depends on age-specific CD4 count.¹²

Prophylaxis for other infections is also sometimes used, either to prevent primary infection or recurrence. See current guidelines.^13,14

Highly active antiretroviral therapy (HAART)

Treatment options have improved significantly in the last 10 years and, as for adults, the mainstay of treatment is a potent combination of antiretroviral drugs:

• HAART has significantly reduced the incidence of opportunistic infection in children and reduced mortality rates by 80-90%.¹⁵
• The drugs used will vary according to the current guidelines.^14,16,17
• Currently triple therapy is usual but those with a very high viral load or symptomatic disease may commence on quadruple therapy.

• This is highly controversial. Some favour early agressive treatment with the aim of controlling viral replication and genetic mutation that may promote drug resistance ultimately.¹⁹ Others promote delay citing the benefits of reduced drug selection pressure, greater adherence and less side-effects.
• All recommendations are based on cohort studies looking at the risk of progression based on CD4 counts and viral load. Serial measurements and trends, used together with clinical assessments are the most useful indicator.

Anti-retroviral therapy's safety and efficacy has largely been assessed on adult trials although paediatric trials are organised on a pan-European basis via PENTA (paediatric European network for the treatment of AIDS).

In the UK, care has grown up around areas of higher prevalence (i.e. London) and centred around specialist clinics. However, in the last few years, dispersal of migrant families away from the capital has meant that approximately a third of HIV positive children now receive care outside London. With relatively small numbers of children involved, expertise has been shared via national clinical networks.⁶

Immunisation

• Routine schedule but avoid live immunisations (except MMR).
• Children with AIDS may not develop protective immunity from immunisation so seek advice if contact with measles/chickenpox etc.

Nutrition

• Monitor weight and growth. Increase oral supplementation when nutritional deficits are identified.
• Enteral supplementation is sometimes warranted.

• Pneumocystis jiroveci (carinii) and toxoplasmosis are the primary infections seen in infected children with PCP the principle cause of death.
• Lymphocytic interstitial pneumonitis, a condition rarely seen in adults, may cause breathing to become increasingly difficult and require admission to hospital.
• Serious bacterial infections are more common in infected children than adults.
• Severe and recurrent infection with Candida spp.
• HIV encephalopathy.
• Iatrogenic - related to multiple medications' side-effects and interactions.

• Perinatal infection promotes accelerated disease progression in children compared to adults due to relative immaturity of the immune system.
• Children with untreated natural infection progress rapidly to disease and approximately 25% of children develop AIDS in the first year of life. In resource-poor settings, mortality is greater than 50% by 2 years of age.³ A small subset survive longer term:- 25% of maternally infected children surviving past their ninth birthday will be asymptomatic with relatively intact immune systems.¹³
• Prognosis is much worse where a child has already been orphaned and likely to be socially and nutritionally disadvantaged.

1. Prevention of perinatal transmission necessitating appropriate medical and obstetric care through pregnancy and delivery worldwide. The widespread availability of antiretrovirals is an important aspect of PMTCT.²⁰ There is some evidence that their extended use in the postnatal period helps to prevent transmission associated with breast feeding.²¹
2. Education of HIV positive children and adolescents - as HIV infected children survive into young adulthood, they need to be aware of how to manage their developing sexual identity in light of their HIV status.
3. Consider broader responsibilities to all children in terms of HIV prevention. Health professionals may provide STI advice and treatment, without parental knowledge or consent to those under 16 years where:⁹
   • The child understands the advice and its implications.
   • The child cannot be persuaded to tell their parents or to allow you to tell them.
   • The child is very likely to have sex without advice or treatment.
   • The child's physical or mental health will suffer without advice or treatment.
   • It is in the child's best interests.
4. Vaccine development remains an important goal.