Staging of HIV disease

WHO clinical staging of HIV disease in children with confirmed infection is listed below. It is included as Table 4 of the WHO case definitions of HIV.¹  WHO recommends that staging be done only after a definitive diagnosis of HIV infection has been made.

Clinical Stage 1, Asymptomatic

• Asymptomatic
• Persistent generalised lymphadenopathy

Clinical Stage 2, Mild symptoms 

• Unexplained persistent hepatosplenomegaly
• Papular pruritic eruptions
• Fungal nail infection
• Angular cheilitis
• Lineal gingival erythema
• Extensive wart virus infection
• Extensive molluscum contagiosum
• Recurrent oral ulcerations
• Unexplained persistent parotid enlargement
• Herpes zoster
• Recurrent or chronic upper respiratory tract infections
• (otitis media, otorrhoea, sinusitis or tonsillitis)

Clinical Stage 3, Advanced symptoms 

• Unexplained moderate malnutrition or wasting not adequately responding to standard therapy
• Unexplained persistent diarrhoea (14 days or more)
• Unexplained persistent fever (above 37.5°C intermittent or constant, for longer than one month)
• Persistent oral candidiasis (after first 6 to 8 weeks of life)
• Oral hairy leukoplakia
• Acute necrotising ulcerative gingivitis or periodontitis
• Lymph node tuberculosis
• Pulmonary tuberculosis
• Severe recurrent bacterial pneumonia
• Symptomatic lymphoid interstitial pneumonitis
• Chronic HIV-associated lung disease including brochiectasis
• Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 × 10⁹/per litre) and/or chronic thrombocytopaenia (<50 × 10⁹ per litre)

Clinical Stage 4, Severe symptoms 

• Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
• Pneumocystis pneumonia
• Recurrent severe bacterial infections (such as empyema, pyomyositis, bone or joint infection or meningitis but excluding pneumonia)
• Chronic herpes simplex infection (orolabial or cutaneous of more than one month’s duration or visceral at any site)
• Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
• Extrapulmonary tuberculosis
• Kaposi's sarcoma
• Cytomegalovirus infection: retinitis or cytomegalovirus infection affecting another organ, with onset at age older than one month
• Central nervous system toxoplasmosis (after one month of life)
• Extrapulmonary cryptococcosis (including meningitis)
• HIV encephalopathy
• Disseminated endemic mycosis (coccidiomycosis or histoplasmosis)
• Disseminated non-tuberculous mycobacterial infection
• Chronic cryptosporidiosis (with diarrhoea)
• Chronic isosporiasis
• Cerebral or B-cell non-Hodgkin's lymphoma
• Progressive multifocal leukoencephalopathy
• Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

Note: Some additional specific conditions may be included in regional classifications (e.g. disseminated Penicilliosis in Asia, and HIV-associated rectovaginal fistula in Africa, and reactivation of American trypanosomiasis).

In the United States, the 2008 update to Guidelines for the use of antiretroviral agents in pediatric HIV infection contains as Table 1 the 1994 Revised Human Immunodeficiency Virus Pediatric Classification System: Clinical Categories, which is largely unchanged in content. The ranking of a number of symptoms is somewhat different than that made in the WHO listing. Staging categories are: N, not symptomatic; A, mildly symptomatic; B, moderately symptomatic; and C, severely symptomatic.²

The US Centers for Disease Control and Prevention (CDC) provided a revised classification system for paediatric HIV infection in 1994.³ This version was updated by the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children and currently appears as Table 6 of the 2010 paediatric guidelines.²

1994 Revised Human Immunodeficiency Virus Pediatric Classification System: Clinical Categories (Updated February 28, 2008 )

Category N: Not Symptomatic

Children who have no signs or symptoms considered to be the result of HIV infection or who have only one of the conditions listed in category A.

Category A: Mildly Symptomatic

• Children with two or more of the following conditions but none of the conditions listed in categories B and C:
• Lymphadenopathy (≥0.5 cm at more than two sites; bilateral = one site)
• Hepatomegaly
• Splenomegaly
• Dermatitis
• Parotitis
• Recurrent or persistent upper respiratory infection, sinusitis, or otitis media.

Category B: Moderately Symptomatic

Children who have symptomatic conditions, other than those listed for category A or category C, that are attributed to HIV infection. Examples of conditions in clinical category B include, but are not limited to, the following:

• Anemia (<8 gm/dL), neutropenia (<1,000 cells/mm³), or thrombocytopenia (<100,000 cells/mm³) persisting ≥30 days
• Bacterial meningitis, pneumonia, or sepsis (single episode)
• Candidiasis, oropharyngeal (i.e., thrush) persisting for >2 months in children aged >6 months
• Cardiomyopathy
• Cytomegalovirus infection with onset before age one month
• Diarrhea, recurrent or chronic
• Hepatitis
• Herpes simplex virus (HSV) stomatitis, recurrent (i.e., more than two episodes within one year)
• HSV bronchitis, pneumonitis, or oesophagitis with onset before age one month
• Herpes zoster (i.e. shingles) involving at least two distinct episodes or more than one dermatome
• Leiomyosarcoma
• Lymphoid interstitial pneumonia (LIP) or pulmonary lymphoid hyperplasia complex
• Nephropathy
• Nocardiosis
• Fever lasting >1 month
• Toxoplasmosis with onset before age one month
• Varicella, disseminated (i.e. complicated chickenpox).

Category C: Severely Symptomatic

Children who have any condition listed in the 1987 surveillance case definition for acquired immunodeficiency syndrome (below), with the exception of LIP (which is a category B condition)

• Serious bacterial infections, multiple or recurrent (i.e. any combination of at least two culture-confirmed infections within a two-year period), of the following types: septicemia, pneumonia, meningitis, bone or joint infection, or abscess of an internal organ or body cavity (excluding otitis media, superficial skin or mucosal abscesses, and indwelling catheter-related infections)
• Candidiasis, oesophageal or pulmonary (bronchi, trachea, lungs)
• Coccidioidomycosis, disseminated (at site other than or in addition to lungs or cervical or hilar lymph nodes)
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis or isosporiasis with diarrhoea persisting >1 month
• Cytomegalovirus disease with onset of symptoms at age >1 month (at a site other than liver, spleen, or lymph nodes)
• Encephalopathy (at least one of the following progressive findings present for at least two months in the absence of a concurrent illness other than HIV infection that could explain the findings): a) failure to attain or loss of developmental milestones or loss of intellectual ability, verified by standard developmental scale or neuropsychological tests; b) impaired brain growth or acquired microcephaly demonstrated by head circumference measurements or brain atrophy demonstrated by computerized tomography or magnetic resonance imaging (serial imaging is required for children <2 years of age); c) acquired symmetric motor deficit manifested by two or more of the following: paresis, pathologic reflexes, ataxia, or gait disturbance
• Herpes simplex virus infection causing a mucocutaneous ulcer that persists for >1 month; or bronchitis, pneumonitis, or oesophagitis for any duration affecting a child >1 month of age
• Histoplasmosis, disseminated (at a site other than or in addition to lungs or cervical or hilar lymph nodes)
• Kaposi's sarcoma
• Lymphoma, primary, in brain
• Lymphoma, small, noncleaved cell (Burkitt's), or immunoblastic or large cell lymphoma of B-cell or unknown immunologic phenotype
• Mycobacterium tuberculosis, disseminated or extrapulmonary
• Mycobacterium, other species or unidentified species, disseminated (at a site other than or in addition to lungs, skin, or cervical or hilar lymph nodes)
• Mycobacterium avium complex or Mycobacterium kansasii, disseminated (at site other than or in addition to lungs, skin, or cervical or hilar lymph nodes)
• Pneumocystis jiroveci pneumonia
• Progressive multifocal leukoencephalopathy
• Salmonella (nontyphoid) septicemia, recurrent
• Toxoplasmosis of the brain with onset at >1 month of age
• Wasting syndrome in the absence of a concurrent illness other than HIV infection that could explain the following findings: a) persistent weight loss >10% of baseline; OR b) downward crossing of at least two of the following percentile lines on the weight-for-age chart (e.g. 95th, 75th, 50th, 25th, 5th) in a child ≥1 year of age; OR c) <5th percentile on weight-for-height chart on two consecutive measurements, ≥30 days apart PLUS 1) chronic diarrhoea (i.e., ≥ two loose stools per day for >30 days), OR 2) documented fever (for ≥30 days, intermittent or constant).