See also separate article Management of HIV in Pregnancy.
HIV infection in young children most commonly arises as a result of mother-to-child transmission (MTCT). It is thought that only 1.5-2% of MTCT occurs transplacentally during pregnancy. The vast majority occurs due to maternofetal transmission of blood during parturition or postnatal breast-feeding. A negative maternal HIV test at booking does not preclude neonatal infection - maternal infection and seroconversion can occur at any time during pregnancy and lactation. This is well-documented in countries with a high prevalence of HIV and has been seen in the UK.
Other routes of infection, such as precocious intravenous drug use or sexual abuse/activity, should be borne in mind as rarer scenarios, which become increasingly common as children approach adolescence.
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.
The World Health Organization (WHO) estimates that in 2005 there were approximately 2.3 million worldwide cases of childhood HIV infection:
- 90% (2.1 million) of HIV positive children live in sub-Saharan Africa.
- In the UK, the unlinked anonymous surveillance programme of 2006 revealed that 1 in 440 women giving birth in England and Scotland were HIV-positive.
- 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%).
- The prevalence of HIV in UK-born women has increased by 66% from 1997 to 2006.
- The prevalence outside London has increased eightfold between 1997 and 2006.
- Without intervention, between 25-40% of babies born to HIV-infected mothers in the most severely affected countries are also infected. With appropriate interventions, transmission rates can be reduced to less than 1%.
- Voluntary confidential reporting mechanisms found 1,650 cases of HIV infection in children under 15 years old, with 77% of these cases due to mother-to-child transmission (MTCT).
- In UK-resident HIV-positive children (between 2003-6), 64% had been born abroad.
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The following factors increase the risk of MTCT:
- Higher levels of maternal viraemia.
- HIV core antigens.
- Lower maternal CD4 count.
- Primary HIV Infection occurring during pregnancy.
- Co-existing other sexually transmitted disease.
- Invasive intrapartum procedures, eg fetal scalp electrodes, forceps, ventouse.
- Rupture of membranes (especially if delivery is more than 4 hours after the membranes ruptured).
- Vaginal delivery.
- Advanced maternal age.
- The firstborn of twins (born to an HIV-infected mother).
- Preterm birth.
- Female babies more likely to be infected early (transplacental/perinatal routes).
- Co-existent malaria may increase HIV transmission rates although this is not firmly established, with conflicting study results. HIV-malaria co-infected mothers are more prone to complications such as anaemia and have a higher malaria parasitaemia and HIV viral-load counts. The co-existence of HIV with malaria in sub-Saharan Africa is thought to increase the malaria parasite biomass.
It is to be hoped that most cases of UK-based HIV infection in pregnant mothers will identified before delivery, so that HIV infection of the child is unlikely/anticipated. However, appropriate vigilance and suspicion of HIV infection in unwell children is important.
Impairment of cellular immune defences (the type found in HIV infection) should be suspected in children who present with:
- Recurrent bacterial infections, particularly invasive infections like meningitis, septicaemia and pneumonia.
- Recurrent/frequent common childhood infections such as otitis media, chest infection, urinary tract infections, sinusitis.
- Unusual infections such as Mycobacterium avium complex (MAC), Pneumocystis jirovecii pneumonia.
- Persistent oral candidiasis that fails to respond to standard therapy.
- Recurrent or severe viral infections, eg herpes simplex, herpes varicella-zoster infection as shingles, cytomegalovirus (CMV) retinitis.
- Growth failure, failure to thrive or generalised wasting with no obvious nutritional, metabolic, endocrine or other cause.
- Developmental delay, particularly language impairment, may suggest HIV-encephalopathy.
- Developmental regression caused by HIV-encephalopathy or opportunistic central nervous system (CNS) infection, eg Toxoplasma gondii.
- Older children may show subtle diminution in intellectual skills such as concentration and memory, or schooling problems, due to HIV-encephalopathy.
- Unusual rashes; erythematous, papular rash due to HIV dermatitis, shingles rash, candidal dermatitis with marked erythema, purpura/bruising in rare cases of HIV-induced thrombocytopenia.
- Parotid enlargement, large tonsils, oral aphthous ulcers, oral/pharyngeal plaques due to thrush or leukoplakia, CMV retinitis.
- Signs of congestive cardiac failure due to cardiomyopathy. Peripheral oedema can also be caused by hypoalbuminaemia due to HIV nephropathy or malnutrition due to gastrointestinal dysfunction.
- Hepatomegaly and splenomegaly are relatively common findings in HIV-infected children.
- Causes of growth impairment or failure to thrive.
- Causes of developmental delay or regression.
- Other causes of childhood anaemia ± immunosuppression.
- Bruton's agammaglobulinaemia or transient hypogammaglobulinaemia of infancy.
- Common variable immunodeficiency.
- Causes of lymphadenopathy.
- Intestinal malabsorption.
- Neglect or malnutrition of child.
- Infectious mononucleosis.
- Severe combined immunodeficiency.
- Thymic aplasia.
- Primary tuberculosis (TB).
- Metabolic childhood disease, eg organic acidurias.
- Primary dermatological disease.
- Cystic fibrosis.
Expectant mothers should be offered routine screening for HIV infection during pregnancy. Those with positive results should be referred to a centre with expertise in managing the mother's HIV diagnosis and the pregnancy, in order to reduce the likelihood of mother-to-child transmission (MTCT).
Testing a child for HIV has large implications for the family, as most cases involve vertical transmission. Information given should be culturally appropriate and interpreters used as needed. See also separate article Consent to Treatment in Children (Mental Capacity and Mental Health Legislation).
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, and early detection of, 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.
- Polymerase chain reaction (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 are performed at diagnosis to assess concurrent infection and risk of different opportunistic infection and can include:
- Serology for hepatitis A, hepatitis B, hepatitis C, Epstein-Barr virus, CMV, herpes simplex virus, mumps, measles, rubella, VDRL and toxoplasmosis.
- Malaria film.
- Mantoux' test/TB cultures.
- Baseline CXR.
- Brain ultrasound/MRI (where there are neurological signs).
- CD4 counts.
- Viral load.
- Screening - audiology, dental, neurodevelopmental, ophthalmology, TB.
- Additional tests in line with drug therapy protocols and clinical status.
Centers for Disease Control and Prevention (CDC) paediatric HIV classification:
- Category N - asymptomatic.
- Category A - mildly symptomatic. 2 or more of:
- 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.
- 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.
In the developing world, management is largely dictated by the availability of healthcare resources and by the lack of recognition of HIV infection in pregnant women. Bottle-feeding may present significant risks in areas where there is poor access to clean, potable drinking water, and needs to be balanced against the reduction in risk of HIV transmission.
Developed world management of HIV-infected pregnant women
- Antiretroviral therapy for expectant mothers, and for newborns (particularly if breast-feeding).
- Short courses of zidovudine or single-dose nevirapine have been shown to be effective in systematic reviews. One study in the US found that adherence rates were low.
- The emergence of multidrug-resistant HIV is challenging.
- New drugs are being developed but there needs to be a balance between reducing the risk of fetotoxicity and preventing mother-to-child transmission (MTCT). One approach is to defer the use of drug therapy until late pregnancy.
- Delivery by Caesarean section in most cases, although vaginal delivery offers no increased risk in carefully selected patients.
- Avoidance of breast-feeding and use of formula milk delivered by bottle.
Neonates born to HIV-infected mothers
- All neonates should be treated with antiretroviral therapy within 4 hours of birth.
- Most neonates should be treated with zidovudine monotherapy but those at high risk of HIV infection should be treated with highly active antiretroviral therapy (HAART).
- Prophylaxis against pneumocystic pneumonia (PCP) is recommended only for neonates at high risk of HIV infection.
Children with confirmed HIV seroconversion
They should receive specialist paediatric infectious-disease management. 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.
Highly active antiretroviral therapy
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%.
- The drugs used will vary according to the current guidelines.
- Currently triple therapy is usual but those with a very high viral load or symptomatic disease may commence on quadruple therapy.
- Pharmacokinetic differences - dosage is usually based on bodyweight and surface area but, in certain instances, a paediatric dose may exceed an adult dose - for example, with protease inhibitors, as a child's hepatic metabolism is more rapid than an adult's.
- Underdosing is likely where doses are not adjusted regularly for growth.
- Children have a relatively immature immune system.
- CD4 counts need to be interpreted differently with different ranges according to age.
- Natural history of AIDS is different in children compared with adults.
- Potentially, children may be exposed to antiretrovirals for much longer periods of time. This is particularly important in view of the lack of long-term data regarding their safety.
- Adherence - when to start antiretroviral therapy critically depends on a child and family's readiness and motivation to embark on long-term complex medication regimes. This is usually dependent on adult caregivers and so it is important to consider supporting the family as a whole rather than the child alone. Children are frequently difficult to administer medications to and many of the drugs have previously not been available as paediatric formulations, adding to problems with compliance. Issues surrounding medication and compliance will be very different in an infant compared with an adolescent.
When should HAART be started in children?
- This is highly controversial. Some favour early aggressive treatment, with the aim of controlling viral replication and genetic mutation that may promote drug resistance ultimately. Others promote delay, citing the benefits of reduced drug selection pressure, greater adherence and fewer 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.
Antiretroviral 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 (ie 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.
Prophylaxis of opportunistic infection
Standardly, HIV-positive infants receive co-trimoxazole for the first year of life (regardless of CD4 count) against Pneumocystis jirovecii pneumonia. Thereafter, its continued use depends on age-specific CD4 count.
Prophylaxis for other infections is also sometimes used, either to prevent primary infection or to avoid recurrence. See current guidelines.
- Routine schedule but avoid live immunisations (except MMR).
- Children with AIDS may not develop protective immunity from immunisation so seek advice if there is contact with measles/chickenpox, etc.
- Monitor weight and growth. Increase oral supplementation when nutritional deficits are identified.
- Enteral supplementation is sometimes warranted.
Future therapies may well be generated by current research, which is looking into efficient inhibition of the HIV infection life cycle.
- Pneumocystis jirovecii 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 with 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. 25% of maternally infected children surviving past their ninth birthday will be asymptomatic with relatively intact immune systems.
- Prognosis is much worse where a child has already been orphaned and likely to be socially and nutritionally disadvantaged.
- Prevention of perinatal transmission necessitating appropriate medical and obstetric care through pregnancy and delivery worldwide. The widespread availability of antiretrovirals is an important aspect in the prevention of mother-to-child transmission (MTCT). There is some evidence that their extended use in the postnatal period helps to prevent transmission associated with breast-feeding.
- 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.
- 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:
- 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.
- Vaccine development remains an important goal.
Further reading & references
- Aidsmap site; UK based charity providing HIV related information for HIV+ individuals and professionals
- MSF Paediatric HIV/AIDS factsheet
- Soilleux EJ, Coleman N; Transplacental transmission of HIV: a potential role for HIV binding lectins. Int J Biochem Cell Biol. 2003 Mar;35(3):283-7.
- Struik SS, Tudor-Williams G, Taylor GP, et al; Infant HIV infection despite "universal" antenatal testing. Arch Dis Child. 2008 Jan;93(1):59-61. Epub 2007 Sep 12.
- Report on the global AIDS epidemic, UNAIDS, 2008
- Global map of prevalence of paediatric HIV/AIDS, World Health Organization (2005)
- A complex picture: HIV and other sexually transmitted infections 2006, Health Protection Agency
- Prendergast A, Tudor-Williams G, Jeena P, et al; International perspectives, progress, and future challenges of paediatric HIV infection. Lancet. 2007 Jul 7;370(9581):68-80.
- Judd A, Doerholt K, Tookey PA, et al; Morbidity, mortality, and response to treatment by children in the United Kingdom and Ireland with perinatally acquired HIV infection during 1996-2006: planning for teenage and adult care. Clin Infect Dis. 2007 Oct 1;45(7):918-24. Epub 2007 Aug 27.
- Biggar RJ, Taha TE, Hoover DR, et al; Higher in utero and perinatal HIV infection risk in girls than boys. J Acquir Immune Defic Syndr. 2006 Apr 1;41(4):509-13.
- ter Kuile FO, Parise ME, Verhoeff FH, et al; The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan Africa. Am J Trop Med Hyg. 2004 Aug;71(2 Suppl):41-54.
- Van Geertruyden JP, Menten J, Colebunders R, et al; The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance. Malar J. 2008 Jul 22;7:134.
- HIV Testing of Children and Young People, Children's HIV Association (CHIVA) , Last revised July 2009
- Revised classification system for HIV infection in children <13>13>, Centers for Disease Control and Prevention (1994)
- Brocklehurst P, Volmink J; Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2002;(2):CD003510.
- Bardeguez AD, Lindsey JC, Shannon M, et al; Adherence to antiretrovirals among US women during and after pregnancy. J Acquir Immune Defic Syndr. 2008 Aug 1;48(4):408-17.
- Madeddu G, Calia GM, Campus ML, et al; Successful prevention of multidrug resistant HIV mother-to-child transmission with enfuvirtide use in late pregnancy. Int J STD AIDS. 2008 Sep;19(9):644-5.
- Brocklehurst P; Interventions for reducing the risk of mother-to-child transmission of HIV infection.; Cochrane Database Syst Rev. 2002;(1):CD000102.
- Read JS, Newell MK; Efficacy and safety of cesarean delivery for prevention of mother-to-child transmission of HIV-1. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD005479.
- Suy A, Hernandez S, Thorne C, et al; Current guidelines on management of HIV-infected pregnant women: impact on mode of delivery. Eur J Obstet Gynecol Reprod Biol. 2008 Aug;139(2):127-32. Epub 2008 Feb 8.
- Management of HIV in Pregnancy, Royal College of Obstetricians and Gynaecologists (June 2010)
- 0-18 years guidance: Other sources of information and guidance, General Medical Council (various dates)
- Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, National Institutes of Health, July 2008; US HAART guidelines for children
- HIV/AIDS Prevention and Treatment, Recommendations and Guidelines, Centers for Disease Control & Prevention
- Neely M, Kovacs A; Management of antiretroviral therapy in neonates, children, and adolescents.; Curr HIV/AIDS Rep. 2004 Jun;1(2):97-104.
- Sharland M, Blanche S, Castelli G, et al; PENTA guidelines for the use of antiretroviral therapy, 2004. HIV Med. 2004 Jul;5 Suppl 2:61-86.
- Menson EN, Walker AS, Sharland M, et al; Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study.; BMJ. 2006 May 20;332(7551):1183-7.
- Patel K, Hernan MA, Williams PL, et al; Long-term effects of highly active antiretroviral therapy on CD4+ cell evolution among children and adolescents infected with HIV: 5 years and counting. Clin Infect Dis. 2008 Jun 1;46(11):1751-60.
- Grimwade K, Swingler GH; Cotrimoxazole prophylaxis for opportunistic infections in children with HIV infection.; Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003508.
- Wang Q, Pang S; An intercellular adhesion molecule-3 (ICAM-3) -grabbing nonintegrin (DC-SIGN) efficiently blocks HIV viral budding. FASEB J. 2008 Apr;22(4):1055-64. Epub 2007 Oct 25.
- Volmink J, Siegfried NL, van der Merwe L, et al; Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD003510.
- Kumwenda NI, Hoover DR, Mofenson LM, et al; Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med. 2008 Jul 10;359(2):119-29. Epub 2008 Jun 4.
|Original Author: Dr Laurence Knott||Current Version: Dr Hayley Willacy|
|Last Checked: 18/02/2011||Document ID: 1275 Version: 26||© EMIS|
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