Elsevier

The Lancet

Volume 370, Issue 9581, 7–13 July 2007, Pages 68-80
The Lancet

Seminar
International perspectives, progress, and future challenges of paediatric HIV infection

https://doi.org/10.1016/S0140-6736(07)61051-4Get rights and content

Summary

Paediatric HIV infection is a growing health challenge worldwide, with an estimated 1500 new infections every day. In developed countries, well established prevention programmes keep mother-to-child transmission rates at less than 2%. However, in developing countries, where transmission rates are 25–40%, interventions are available to only 5–10% of women. Children with untreated natural infection progress rapidly to disease, especially in resource-poor settings where mortality is greater than 50% by 2 years of age. As in adult infection, antiretroviral therapy has the potential to rewrite the natural history of HIV, but is accessible only to a small number of children needing therapy. We focus on the clinical and immunological features of HIV that are specific to paediatric infection, and the formidable challenges ahead to ensure that all children worldwide have access to interventions that have proved successful in developed countries.

Section snippets

Prevention

The most effective way to address the paediatric HIV pandemic is prevention of mother-to-child transmission. However, most infected infants are born to women who are unaware of their status.15 Voluntary counselling and testing is a prerequisite to enable women to access programmes for prevention of mother-to-child transmission.15 Transmission can be reduced substantially in resource-poor settings, as reviewed elsewhere,16, 17, 18 but only 5–10% of pregnant women have access to such strategies.1

Natural history of paediatric HIV infection

Most paediatric HIV infections are acquired through mother-to-child transmission,33 although infection via contaminated blood products or tissue, unsafe injection, or incision practices, and sexual abuse also takes place.34, 35, 36 In adolescents, horizontal spread through sexual contact and injection drug use are also substantial methods of transmission.33, 37

The overall risk of mother-to-child transmission without interventions is 15–30% in Europe and USA38, 39, 40 but 25–40% in sub-Saharan

Immune control

The immune system can contain HIV, at least temporarily, and, in some instances, long term. CD8+ cytotoxic T lymphocytes (CTL)82, 83, 84 play a central part in this HIV-specific immune response (figure).82, 84, 85, 86, 87 The most direct evidence comes from studies in the simian-immunodeficiency-virus-macaque model, in which anti-CD8 monoclonal antibody infusions showed that CD8+ T cells mediate the decline in acute viraemia in adult infection, and contribute to maintenance of the viral

Management

Identification of HIV-infected children by reliable, affordable techniques is essential to enable early institution of prophylaxis and treatment. The simplest laboratory test, used to diagnose HIV infection in adults, is an antibody test (usually by ELISA). Although this test is suitable for children older than 18 months, up to this time transplacental-maternal antibody persists, and a positive result is therefore diagnostic only of maternal infection. The gold standard for children under 18

Search strategy and selection criteria

We considered published material pertinent to the review topic, in addition to relevant publications identified by searching PubMed using the search term “paediatric HIV” or “HIV” in combination with “Africa”, “diagnosis”, “treatment”, “prophylaxis”, “mother-to-child transmission”, “cytotoxic T lymphocyte”, and “antibody”. Reference lists within articles identified by this search strategy were also searched. Review articles and book chapters have been included where appropriate because

References (181)

  • AS Malin et al.

    Pneumocystis carinii pneumonia in Zimbabwe

    Lancet

    (1995)
  • PM Jeena et al.

    Effects of the human immunodeficiency virus on tuberculosis in children

    Tuber Lung Dis

    (1996)
  • C Chintu et al.

    Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study

    Lancet

    (2002)
  • J Whitworth et al.

    Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study

    Lancet

    (2000)
  • Z Bentwich et al.

    Immune activation is a dominant factor in the pathogenesis of African AIDS

    Immunol Today

    (1995)
  • R Geffin et al.

    A longitudinal assessment of autologous neutralizing antibodies in children perinatally infected with human immunodeficiency virus type 1

    Virology

    (2003)
  • AIDS Epidemic Update, December, 2006

  • Five year follow up of vertically HIV infected children in a randomised double blind controlled trial of immediate versus deferred zidovudine: the PENTA 1 trial

    Arch Dis Child

    (2001)
  • M De Martino et al.

    Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in children and the Italian national AIDS registry

    JAMA

    (2000)
  • DM Gibb et al.

    Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland

    BMJ

    (2003)
  • SL Gortmaker et al.

    Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1

    N Engl J Med

    (2001)
  • F Dabis et al.

    18-Month mortality and perinatal exposure to zidovudine in West Africa

    AIDS

    (2001)
  • EM Obimbo et al.

    Predictors of early mortality in a cohort of human immunodeficiency virus type 1-infected African children

    Pediatr Infect Dis J

    (2004)
  • The world health report: make every mother and child count

    (2005)
  • Treating 3 million by 2005. Making it happen: the WHO strategy

  • JT Boerma et al.

    Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage

    Bull World Health Organ

    (2006)
  • Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy

    Clin Infect Dis

    (2005)
  • Unpublished quarterly surveillance tables number 70, 06/1, table 13b

  • Achievements in Public Health: Reduction in Perinatal Transmission of HIV Infection—United States, 1985–2005

    MMWR Morb Mortal Wkly Rep

    (2006)
  • S Nightingale et al.

    Evidence behind the WHO guidelines: hospital care for children: what antiretroviral agents and regimens are effective in the prevention of mother-to-child transmission of HIV?

    J Trop Pediatr

    (2006)
  • J McIntyre

    Strategies to prevent mother-to-child transmission of HIV

    Curr Opin Infect Dis

    (2006)
  • Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants in resource-limited settings: towards universal access. A public health approach

    (2006)
  • A Coutsoudis et al.

    Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis

    J Infect Dis

    (2004)
  • R Nduati et al.

    Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial

    JAMA

    (2000)
  • TE Taha et al.

    Late postnatal transmission of HIV-1 and associated factors

    J Infect Dis

    (2007)
  • Creek T, Arvelo W, Kim A, et al. Role of infant feeding and HIV in a severe outbreak of diarrhoea and malnutrition...
  • Onyango C, Mmiro F, Bagenda D, et al. Early breastfeeding cessation among HIV-exposed negative infants and risk of...
  • PJ Iliff et al.

    Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival

    AIDS

    (2005)
  • Consensus statement. WHO HIV and infant feeding technical consultation held on behalf of the inter-agency task team (IATT) on prevention of HIV infections in pregnant women, mothers and their infants. Geneva, Oct 25–27, 2006

  • New data on the prevention of mother-to-child transmission of HIV and their policy implications: conclusions, and implications. WHO Technical Consultation on behalf of the UNFPA/UNICEF/WHO/UNAIDS Inter-Agency Task Team on Mother-to-Child Transmission of HIV. Geneva, October 11–13, 2000. Report No. WHO/RHR/01.28

  • SU Hartmann et al.

    Alternative modified infant-feeding practices to prevent postnatal transmission of human immunodeficiency virus type 1 through breast milk: past, present, and future

    J Hum Lact

    (2006)
  • CM Wilfert et al.

    Balancing maternal and infant benefits and the consequences of breast-feeding in the developing world during the era of HIV infection

    J Infect Dis

    (2007)
  • GC John-Stewart

    Breast-feeding and HIV-1 transmission—how risky for how long?

    J Infect Dis

    (2007)
  • Report on the global AIDS epidemic

  • EM Lackritz

    Prevention of HIV transmission by blood transfusion in the developing world: achievements and continuing challenges

    AIDS

    (1998)
  • ML Lindegren et al.

    Sexual abuse of children: intersection with the HIV epidemic

    Pediatrics

    (1998)
  • Cases of HIV infection and AIDS in the United States, 2004. HIV/AIDS surveillance report, volume 16

  • Epidemiology, clinical features, and prognostic factors of paediatric HIV infection

    Lancet

    (1988)
  • Risk factors for mother-to-child transmission of HIV-1

    Lancet

    (1992)
  • SR Nesheim et al.

    A prospective population-based study of HIV perinatal transmission

    AIDS

    (1994)
  • View full text