Page 24
infection can be identified by recent appearance of HIV antibody or by identifying viral products (HIV-RNA or HIV-DNA and/or ultrasensitive HIV p24 antigen) with negative (or weakly reactive) HIV antibody. Initially in 1990, a four-stage clinical staging system was developed for clinical purposes and only for adults. Subsequently in 2002, a three-stage system for children was proposed to support rolling out ART. This publication revises the 2003 WHO clinical staging of HIV related disease in infants and children, which is now harmonized with the 1990 classification of disease for adults and adolescents. This is similar to the four-stage clinical classification of the United States CDC revised in 1994 and originally intended for surveillance purposes. Both the United States CDC and WHO clinical classifications recognize primary HIV infection. It is also proposed that the appearance of newor recurrent clinical staging events or immunodeficiency be used to assess individuals once they are receiving ART. Clinical assessment prior to treatment Clinical staging is used once HIV infection has been confirmed (serological and/or virological evidence of HIV infection). An additional presumptive clinical diagnosis of severe HIV disease (equivalent to severe immunodeficiency) among infants younger than 18 months is suggested for use in situations in which definitive virological diagnosis of HIV infection is not readily available. The clinical events used to categorize HIV disease among infants, children, adolescents or adults living with HIV are divided into those for which a presumptive clinical diagnosis may be made (where syndromes or conditions can be diagnosed clinically or with basic ancillary investigations) and those requiring a definitive diagnosis (generally conditions described according to causation requiring more complex or sophisticated laboratory confirmation). The clinical stage in simplified terms describing the spectrum of HIV related symptomatology, asymptomatic, mild symptoms, advanced symptoms and severe symptoms. The clinical stage is useful for assessment at baseline (first diagnosis of HIV infection) or entry into long-term HIV care and in the follow-up of patients in care and treatment programmes. It should be used to guide decisions on when to start co-trimoxazole prophylaxis and other HIV related interventions, including when to start antiretroviral therapy. The clinical stages have been shown to be related to survival, prognosis and progression of clinical disease without antiretroviral therapy in adults and children. Clinical assessment of people receiving antiretroviral therapy Treatment with potent and effective antiretroviral therapy regimens can reverse and improve clinical status in keeping with immune recovery and suppression of viral load. New or recurrent clinical staging events once people are receiving antiretroviral therapy for more than 24 weeks may be used to guide decision-making, particularly when the CD4 count is not available. It is assumed that the clinical staging events remain significant among people receiving antiretroviral therapy as they are among children and adults before the start of antiretroviral therapy. In the first 24 weeks of starting an antiretroviral therapy regimen, clinical events appear largely due to immune reconstitution (or the toxicity of antiretroviral therapy); after 24 weeks, clinical events usually reflect immune deterioration. However, the monitoring of disease progression and response to therapy using clinical staging events urgently needs to be validated. Immunological assessment The pathogenesis of HIV infection is largely attributable to the decrease in the number of T cells (a specific type of lymphocyte) that bear the CD4 receptor (CD4+). The immune status of a child or adult living with HIV can be assessed by measuring the absolute number (per mm3 ) or percentage of CD4+ cells, and this is regarded as the standard way to assess and characterize the severity of HIV-related immunodeficiency. Progressive depletion of CD4+ T cells is associated with progression of HIV disease and an increased likelihood of opportunistic infections and other clinical events associated with HIV, including wasting and death. Immune status in children The absolute CD4 cell count and the %CD4+ in