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Discussion

Background

The World Health Organization (WHO) first developed a case definition for AIDS in adults in 1986[1]. This case definition was subsequently revised and expanded to include a case definition for AIDS in children and infants. The WHO also introduced systems for classifying HIV disease by clinical and immunological parameters, with subsequent revisions. The WHO last published updates to these case definitions and staging criteria in 2007[2]. The WHO HIV Case Definitions are primarily designed for surveillance purposes, whereas the WHO Staging Systems (Clinical and Immunological) are intended to assist clinicians in managing individuals already diagnosed with HIV infection.

WHO HIV Case Definitions

The WHO HIV case definitions are intended to provide uniform definitions for use in HIV surveillance efforts globally. In the 2007 guidelines, the WHO defines a case of HIV infection as "an individual with HIV infection irrespective of clinical stageā€¦confirmed by laboratory criteria according to country definitions and requirements[2]". The presence of signs or symptoms consistent with HIV infection or Acquired Immune Deficiency Syndrome (AIDS) is no longer considered sufficient for the HIV case definition; suspected cases must a have laboratory confirmed positive HIV test (antibody or virologic). The 2007 WHO case definitions have specific criteria for two groups: (1) adults and children 18 months or older and (2) children younger than 18 months (Figure 1). In addition, the WHO has developed a case definition for Advanced HIV Infection, which is also used for reporting and surveillance purposes (Figure 2). Importantly, this case definition extends beyond just AIDS cases, as it includes HIV-infected persons with WHO Stage 3 conditions, adults with absolute CD4 counts less than 350 cells/mm3, and children with similarly low CD4 percentages. Difficulties with accurate AIDS case reporting have led the WHO to now recommend that AIDS case reporting for surveillance is no longer required if HIV infection or advanced HIV infection is reported[2]. Recognizing the challenges of making a diagnosis of HIV disease in infants without virological HIV testing, the 2007 WHO document provides clinical criteria for making a presumptive diagnosis of severe HIV disease in infants and children less than 18 months of age in situations where virological HIV testing is not available (Figure 3).

WHO Staging Systems

The WHO has developed and refined a system for staging HIV disease by both clinical and immunological criteria, which was also updated in 2007[2]. Both the Clinical and Immunological classification systems use a four-stage system for both adults and children, with higher numbers reflecting higher degrees of deterioration in clinical and/or immunological status.

Clinical Staging of HIV Disease

The WHO clinical staging system is generally summarized in Figure 4; more detailed clinical staging criteria for adults and children are presented in Figure 5Clinical Stage 1Clinical Stage 2Clinical Stage 3Clinical Stage 4Source and Figure 6Clinical Stage 1Clinical Stage 2Clinical Stage 3Clinical Stage 4Source, respectively. Assessment of the clinical stage of people living with HIV should be performed at every health care encounter, as changes in the clinical stage can have significant implications for that individual's care and treatment plan.

Immunological Staging of HIV Disease

The severity of HIV-related immunodeficiency can be estimated by measuring the level of CD4+ T cells in the peripheral circulation. The peripheral CD4+ T-cell count, or CD4 count, of an HIV-infected individual provides clinically relevant prognostic information for that individual. For this reason, guidelines on the clinical management of people living with HIV typically base their recommendations on both the clinical and immunological status of the HIV-infected individual. The most current WHO immunological staging system delineates four stages of immunodeficiency, depending upon the peripheral CD4 count, expressed as either an absolute number of a percentage of the total lymphocyte count (Figure 7). Given the relative inaccuracy of absolute CD4 counts in young children, the staging criteria are stratified by age.

Clinical Application of the WHO Staging Systems

Whereas the WHO HIV case definitions were designed primarily for surveillance purposes, the Clinical and Immunological staging systems are intended to assist clinicians in providing care and treatment to people living with HIV. Clinical guidelines on HIV management, including those published by the WHO[3,4] use clinical and/or immunological benchmarks for pivotal treatment decisions (for example, when to initiate antiretroviral therapy). Accurate staging of people living with HIV is therefore critically important for optimal disease management.

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    Figure 1. WHO Case Definitions for HIV Infection

    Source: World Health Organization. Case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. WHO, 2007.


    Figure 1
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    Figure 2. WHO Clinical Criteria for Diagnosis of Advanced HIV (including AIDS<sup>a</sup>)

    Source: World Health Organization. Case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. WHO, 2007.


    Figure 2
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    Figure 3. WHO Clinical Criteria for Presumptive Diagnosis of Severe HIV Disease Among Infants and Children Aged under 18 Months in Situations where Virological Testing is not Available

    Source: World Health Organization. Case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. WHO, 2007.


    Figure 3
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    Figure 4. WHO Clinical Staging of Established HIV Infection

    Source: World Health Organization. Case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. WHO, 2007.


    Figure 4
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    Figure 5: WHO Clinical Staging of HIV Disease for Adults & Adolescents with Confirmed HIV Infection. Image 1. Clinical Stage 1
    Figure 5 (series)


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    Figure 6: WHO Clinical Staging of HIV Disease for Children with Confirmed HIV Infection. Image 1. Clinical Stage 1
    Figure 6 (series)


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    Figure 7. WHO Immunological Classification for Established HIV Infection

    Source: World Health Organization. Case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. WHO, 2007.


    Figure 7