Introduction to Clinical Staging and Surveillance Case Definitions for HIV infection

Introduction to Clinical Staging and Surveillance Case Definitions for HIV infection

What you

By the end of this unit, you should be able to:

• 
  describe the revised (2006) WHO HIV clinical staging criteria and the presumptive and definitive criteria
  
• 
  describe the revised (2006) WHO surveillance case definitions
  
• 
  explain the link between HIV clinical staging, antiretroviral treatment recommendations and HIV case surveillance.
  

Clinical staging criteria for HIV and AIDS were developed to:

• 
  provide uniformity for clinical evaluation of persons with HIV infection
  
• 
  act as an indicator of prognosis
  
• 
  guide clinical management of patients
  
• 
  help study the natural history of HIV infection.
  

The Walter Reed staging classification system was developed in 1986 for use in United States military personnel. This staging system included both clinical and laboratory manifestations of HIV disease. The inclusion of a laboratory component and the list of AIDS opportunistic illness in the Walter Reed staging classification system worked well in developed countries, but were not suitable for developing countries.

case definitions

The initial WHO AIDS surveillance case definition (Bangui) was developed in 1986 and was designed for use in developing countries. It was modified in 1989 to include HIV serologic criteria for use in areas with laboratory capacity. It was further modified in 1994 in response to changes in the European Centres for Disease Control and Prevention surveillance case definitions. The WHO has not previously developed a surveillance case definition for HIV disease alone (that is, persons with HIV infection who do not meet the surveillance case definition of AIDS).
Updated clinical

staging system

The increased availability of ART has resulted in the need for an updated HIV clinical staging system that:

• 
  harmonises the 2002 three-stage paediatric staging system with the 1990 four-stage adult system
  
• 
  includes stages at which prophylactic and antiretroviral therapy should be considered and recommended
  

Anticipating wider distribution of ART, WHO convened a panel of experts in 2004 to develop updated clinical staging systems for adults and children. Regional consultations were held throughout 2005, including one at PAHO in October, 2005. The revisions to clinical staging systems were adopted in 2006. The revisions are intended to capture the treatable nature of HIV infection in the presence of ART. Clinical staging should be done at the time of initial HIV diagnosis, upon entry into clinical care for HIV infection and at each clinical visit.

HIV-associated symptomatology	WHO Clinical Stage
Asymptomatic	1
Mild symptoms	2
Advanced symptoms	3
Severe symptoms	4

The 2006 WHO clinical staging criteria and presumptive and definitive criteria for recognising HIV-related clinical events in adults and children can be found in Annexes 6.1 through 6.4, as shown in Table 4.4, on the next page.

Annex	Information provided
4.1	WHO clinical staging of HIV/AIDS for adults and adolescents with confirmed HIV infection (2006)
4.2	WHO clinical staging of HIV/AIDS for infants and children with confirmed HIV infection (2006)
4.3	Presumptive and definitive criteria for recognising HIV/AIDS-related clinical events in HIV-infected adults and adolescents (2006)
4.4	Presumptive and definitive criteria for recognising HIV/AIDS-related clinical events in HIV-infected children (2006)

The revised staging systems include:

• 
  presumptive clinical diagnoses that can be made in the absence of sophisticated laboratory tests
  
• 
  definitive clinical criteria, which require confirmatory laboratory tests.
  

With expansion of laboratory capacity in developing countries, including those in the Caribbean, the WHO developed an immunologic classification system for HIV infection. These criteria are based upon the known decline in CD4 cells with the progression of HIV disease. Listed below are the age-related values and associated degree of immunodeficiency. Note that for children under 5 years of age, the CD4 percent rather than absolute count should be used.

HIV-associated immunodeficiency	Age-related CD4 values
	< 11 months (CD4+ %)	12 – 34 months (CD4+ %)	36-59 months (CD4+ %)	≥ 5 yrs (mm/3)
None/not significant	> 35	> 30	> 25	> 500
Mild	30 - 35	25 – 30	20 – 25	350−499
Advanced	25 - 29	20−24	15−19	200−349
Severe	<25	<20	<15	<200 or <15%

Updated surveillance

case definitions

Changes to the clinical staging of HIV infection, combined with the expanded use of ART, have resulted in a need to revise case surveillance recommendations. Previous case definitions have focused exclusively on reporting persons who met the Bangui or expanded AIDS case definition. WHO now recommends that reporting be expanded to cover the entire spectrum of HIV disease; that is, HIV case surveillance. WHO recommends that countries standardise their reporting practises.

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  all HIV cases (clinical stages 1-4)
  
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  cases with advanced HIV disease (clinical stages 3 and 4)
  
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  cases with AIDS (clinical stage 4).
  

There are two significant reasons to conduct HIV case surveillance:

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  to provide a complete count or estimate of the number of persons with HIV infection (because AIDS case reporting does not include asymptomatic HIV-infected persons)
  
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  to measure the effectiveness of treatment programmes and other interventions.
  

For HIV case surveillance, WHO recommends that HIV cases diagnosed and not previously reported in that country should be reported using a standard case definition such as those presented in Table 4.6

Table 4.6. WHO case surveillance definitions (2006).

Adults and adolescents and children > 18 months

Positive HIV antibody testing (rapid or laboratory based EIA). This is usually confirmed using a second HIV antibody test (rapid or laboratory-based EIA) that relies on different antigens of different operating characteristics than the initial test. The antibody test can be confirmed by virologic testing as well. And / or Positive virologic test for HIV or its components (HIV-RNA or HIV-DNA or ultrasensitive HIV p24 antigen) confirmed by a second virologic test obtained from a separate specimen taken at a different time period.

Children aged below 18 months

Positive virologic test for HIV or its components (HIV-RNA or HIV-DNA or Ultrasensitive HIV p24 antigen) confirmed by a second virologic test obtained from a separate specimen taken more than four weeks after birth.

Table 4.7. WHO advanced HIV case definitions (2006).

Category	Clinical/immunological criteria
Advanced HIV in infants, children, adults and adolescents with documented HIV infection	Presumptive or definitive diagnosis of any one stage 3 or 4 condition (as defined in annex 2.3 and 2.4).
Children > 6 years, adolescents and adults with documented HIV infection	CD4 count less than 350/ mm3.
Children < 6 years with documented HIV infection	%CD4 < 30 in those less than 11 months of age %CD4 < 25 in those aged 12-35 months %CD4 < 20 in those aged 35-59 months.

AIDS case surveillance is not required in countries that conduct reporting of advanced HIV infection. Countries reporting cases of AIDS should use the most recent WHO case definition (clinical stage 4 or CD4 count less than 200 or less than 15%). Reporting should include those persons with AIDS who were not previously reported in that country. Reporting should be done at the time the person is initially diagnosed with AIDS.

There is no standard case definition of primary HIV infection. However, primary HIV infection is of great importance, particularly since it represents recently acquired HIV infection and because persons with primary HIV infection are highly contagious.

RNA or HIV-DNA and/or ultrasensitive HIV p24 antigen) with negative (or weakly reactive) HIV antibody.

Clinical staging and CD4 counts/percents can be used to determine the best time to begin antiretroviral treatment The WHO has developed separate treatment recommendations for use in areas in which CD4 testing is available and areas in which such testing is not available.

If CD4 testing is:	WHO ART recommendation for adults and adolescents
Available	WHO clinical stage 4 (AIDS), regardless of their CD4 count WHO clinical stage 3 whose CD4 count is <350 cells/mm3 WHO clinical stages 1 or 2 when the CD4 count is < 200 cells/mm3
Not available	WHO clinical stage 4 (AIDS) regardless of total lymphocyte count WHO clinical stage 3, regardless of total lymphocyte count WHO clinical stages 2 with a total lymphocyte count < 1200 cells/mm3

As described on the previous page, clinical staging is used:

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  to determine the best time to begin treatment for HIV disease
  
• 
  as a key component of the surveillance case definitions.
  

Systems in which advanced HIV disease is reported (clinical stages 3 and 4) can provide information on the number of patients eligible for ART, whereas HIV case surveillance (reporting of all clinical stages), can provide information on the proportion of HIV diagnoses that are eligible for ART.

review

discussion

Get into small groups to discuss these questions.

1. 
   Discuss the changes made in 1989 and 1994 to the WHO AIDS surveillance case definition (Bangui)? Why were these changes made?
   

2. 
   In 2006, the WHO adopted an updated HIV/AIDS clinical staging system and surveillance case definition. Why was an updated HIV/AIDS clinical staging system necessary?
   

3. 
   What does the revised staging system include?
   

4. 
   Although there is no standard case definition for primary HIV infection, what can be learned from reports of persons with primary HIV infection?
   

Work on this case study independently.

1. 
   As an HIV surveillance officer for Cariba, you are charged with standardising the country’s HIV reporting practises. What processes would you implement to insure that HIV case surveillance is standardised?
   

2. 
   Cariba recently began providing free antiretroviral therapy to HIV-infected individuals and uses the WHO antiretroviral treatment recommendations to determine the best time to begin antiretroviral therapy.
   

1. 
   In the Northern District of Cariba, CD4 testing is available. What are the WHO recommendations for when adults and adolescents should begin ART?
   

2. 
   In the Western District of Cariba CD4, testing is not available. What are the WHO recommendations for when adults and adolescents should begin ART?