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Congenital HIV Infection and its Prevention

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See also: related article on Childhood AIDS.

HIV infection in young children most commonly arises as a result of vertical transmission (or mother to child transmission – MTCT)., Other routes of infection such as precocious intravenous drug use or sexual abuse/activity should be borne in mind as rarer scenarios, and become increasingly common as children approach adolescence. It is thought that only 1.5–2% of MTCT occurs transplacentally during pregnancy.1 The vast majority occurs due to maternofetal transmission of blood during parturition or post-natal breastfeeding.

Correct management using anti-retrovirals, the correct method of delivery and avoidance of breastfeeding can massively reduce the chances of MTCT in a given pregnancy. Unfortunately, the prevailing socio-economic conditions in many parts of the world most severely affected by HIV and AIDS are such that these measures are currently difficult to implement. Political as well as medical will is needed to reduce the worldwide incidence of unnecessary congenital HIV infection, to reduce the burden of disease caused by this global pandemic.

Even in the developed world, one cannot afford to be complacent as there is no guarantee that patients will comply with screening and treatment programs, even if they are available.2

Epidemiology

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. The prevalence outside London has increased eightfold between 1997 and 2006.. Sub-Saharan African born pregnant women living outside London had a significantly higher HIV prevalence (3.5%) in 2006 than those living inside London (2.1%).The prevalence of HIV in UK born women has increased by 66% from 1997 to 2006. Voluntary confidential reporting mechanisms found 1,650 cases of HIV-infection in children under15, with 77% of these cases due to MTCT. It was estimated that in 2006 about 90% of all HIV-infected women giving birth in England and Scotland were diagnosed before delivery due to the routine offering and recommendation of antenatal HIV-testing.

A study at the UCL Institute of Child Health found that Injecting drug use as the reported risk factor for maternal HIV acquisition declined from 49.2% in 1990-1993 to 3.1% in 2004-2006.3
The WHO estimates that in 2003 there were ~700,000 worldwide cases of childhood HIV infection. The overwhelming majority of these were due to MTCT.4 A massive proportion of these cases occurred in relatively impoverished countries. HIV-seroprevalence rates in pregnant women in developing countries can be as high as 5%.5 Approximately 30% of HIV-positive mothers will transmit the infection to their children if they receive no treatment.6

In the US, the annual incidence of MTCT of HIV is estimated at 1,400–2,200 cases, with a HIV seroprevalence rate of around 0.3% among pregnant women, predominantly affecting metropolitan centres.5 US perinatal HIV-transmission rates are 25% and 4% in untreated and treated women respectively.5 Recent figures from Sweden have shown a fall in transmission rates from ~25% in 1985–1993, to 0.6% in 1999–2003, as management of this clinical scenario has improved.7

Risk factors

The following factors have been shown to increase the risk of MTCT:

  • Chronic chorioamnionitis.
  • Early rupture of membranes before delivery.
  • Pre-term birth.
  • Female babies more likely to be infected early (transplacental/perinatal routes).8
  • Co-existent malaria may increase HIV transmission rates though 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.9 The co-existence of HIV with malaria in sub-Saharan Africa is thought to increase the malaria parasite biomass.10

Presentation

Hopefully, most cases of UK-based HIV infection in pregnant mothers will be picked up before delivery so that HIV infection of the child is unlikely/anticipated. However, up to 10% of HIV-positive mothers have slipped through the system in relatively recent times, so appropriate vigilance and suspicion of HIV-infection in unwell children is important. When undetected it may occur as an early infection if transmitted transplacentally or perinatally, or later if transmitted through breastfeeding. Some cases present with an indolent course in later childhood, despite infection having occurred in the fetal, perinatal or infant stages.

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 jiroveci (carinii) pneumonia.
  • Recurrent fungal disease such as thrush that fails to respond to standard therapy.
  • Recurrent or severe viral infections, eg Herpes simplex, Herpes varicella-zoster infection as shingles, 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 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.

Signs of HIV in children

There are no specific HIV signs, but those present are usually due to disease caused by opportunistic infection. Signs may be found in the following systems:

  • Growth/development. Falling off on growth centile charts.
  • Dermatological. Erythematous, papular rash due to HIV dermatitis. Shingles rash. Candidal dermatitis with marked erythema. Purpura/bruising in rare cases of HIV-induced thrombocytopenia.
  • Head, eye, ears, nose and throat (HEENT). Parotid enlargement, large tonsils, oral aphthous ulcers, oral/pharyngeal plaques due to thrush or leukoplakia, CMV retinitis.
  • CVS. 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.
  • RS. Crackles, wheeze and other non-specific findings can be present in PCP pneumonia or Mycoplasma pneumoniae infection - signs of cavitation/lung abscess in cases of TB/cavitating pneumonia (including finger clubbing).
  • Abdomen. Hepatomegaly and splenomegaly are relatively common findings in HIV-infected children.
  • Reticuloendothelial. Persistent generalised or regional lymphadenopathy or gross lymphadenitis due to lymphoma.
  • CNS. Motor delay, abnormalities of muscle tone, spastic diplegia and oral motor dysfunction are signs of HIV encephalopathy. Opportunistic CNS infection can present in a variable fashion.
Differential diagnosis
Investigations

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 her HIV diagnosis and the pregnancy in order to reduce the likelihood of MTCT. Children with HIV may need extensive investigation.

Management

In the developed world the mainstays of management of HIV-infected pregnant women are:

  • Anti-retroviral therapy for expectant mothers, and for newborns (particularly if breastfeeding). Short courses of zidovudine or single-dose nevirapine have been shown to be effective in systematic reviews.11 One study in the US found that adherence rates were low.12 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 MTCT. One approach is to defer the use of drug therapy until late pregnancy.13
  • Delivery by caesarean section in most cases,14,15 although vaginal delivery offers no increased risk in carefully selected patients.16
  • Avoidance of breast feeding and use of formula milk delivered by bottle.

Children with confirmed HIV seroconversion should receive specialist paediatric-infectious-disease management. See separate article on childhood AIDS.
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.

Future therapies may well be generated by current research which is looking into efficient inhibition of the HIV infection life cycle.17

Prognosis

Prevention is far better than cure where HIV and children is concerned. Outlook is significantly worse for children with congenital HIV infection when compared to those infected in later life, despite the enormous advances in prophylactic and anti-opportunistic-infection treatments. Mean survival from diagnosis is about 10 years. About 15% of children suffer rapidly progressive and fatal disease with the remainder split between those with a more chronic course and those who appear to be similar to adults in their ability to tolerate HIV infection and its treatment.5 The tragedy of HIV infection in the developing world is underlined by the fact that 20% of babies born with HIV infection will die before their 4th birthday without treatment, and 50% will not survive past their 9th birthday without treatment.

Prevention

Key strategies include:

  • Prevention of primary HIV infection in women and the prevention of unintended pregnancies in women living with HIV6
  • Offering and high uptake of routine antenatal HIV-testing for pregnant women
  • Adequate management of cases of known HIV in pregnancy and those picked up by screening
  • Wholesale worldwide politico-social changes that address the scarcity of general and HIV-specific healthcare resources in the developing world18


Document references
  1. 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. [abstract]
  2. Ferguson W, Cafferkey M, Walsh A, et al; Targeting Points for Further Intervention: A Review of HIV-Infected Infants Born in Ireland in the 7 Years Following Introduction of Antenatal Screening. J Int Assoc Physicians AIDS Care (Chic Ill). 2008 Jul;7(4):182-6. Epub 2008 Jul 14. [abstract]
  3. Townsend CL, Cortina-Borja M, Peckham CS, et al; Trends in management and outcome of pregnancies in HIV-infected women in the UK and Ireland, 1990-2006. BJOG. 2008 Aug;115(9):1078-86. Epub 2008 May 22. [abstract]
  4. Scarlatti G; Mother-to-child transmission of HIV-1: advances and controversies of the twentieth centuries. AIDS Rev. 2004 Apr-Jun;6(2):67-78. [abstract]
  5. Frye R, Rivera-Hernandez D; HIV Infection. eMedicine, June 2007; Overview of congenital and paediatric HIV infection.
  6. UNAIDS; 2004 Report on the global AIDS epidemic, Bangkok conference.; Proceedings of this international meeting.
  7. Naver L, Lindgren S, Belfrage E, et al; Children Born to HIV-1-Infected Women in Sweden in 1982-2003: Trends in Epidemiology and Vertical Transmission. J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):484-489. [abstract]
  8. 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. [abstract]
  9. 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. [abstract]
  10. 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. [abstract]
  11. Brocklehurst P, Volmink J; Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2002;(2):CD003510. [abstract]
  12. 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. [abstract]
  13. 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. [abstract]
  14. Brocklehurst P; Interventions for reducing the risk of mother-to-child transmission of HIV infection.; Cochrane Database Syst Rev. 2002;(1):CD000102. [abstract]
  15. 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. [abstract]
  16. 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. [abstract]
  17. 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. [abstract]
  18. Little KE, Bland RM, Newell ML; Vertically acquired paediatric HIV infection: the challenges of providing comprehensive packages of care in resource-limited settings. Trop Med Int Health. 2008 Jul 28. [abstract]

Internet and further reading Acknowledgements EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 1275
Document Version: 25
Document Reference: bgp24873
Last Updated: 25 Sep 2008
Planned Review: 25 Sep 2010

The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.

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