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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 healthy infants who are not infected with HIV are considerably higher than those observed in uninfected adults and slowly decline to adult values by the age of about six years. Age must therefore be taken into account as a variable in considering absolute CD4 counts or %CD4+. Among children younger than five years of age, the absolute CD4 count tends to vary within an individual child more than the %CD4+. Currently, therefore, the measurement of the %CD4+ is thought to be more valuable in younger children. Absolute CD4 counts (and less so %CD4+) fluctuate within an individual and depend on intercurrent illness, physiological changes or test variability. Measuring the trend over two or three repeated measurements is therefore more informative than an individual value. Not all the equipment in use in resource-constrained settings can accurately estimate the %CD4+. The dedicated cytometers are designed to exclusively perform absolute CD4 measurements without the need for a haematology analyser and therefore do not provide %CD4+ii . Any classification of immune status has to consider age. The 1994 immunological classification of the United States CDC has previously been used. WHO has proposed a modified immunological classification based on more recent analysis of the prognosis. Analysis of prognosis from 17 studies of children including 3941 children living with HIV from United States and European settings provide estimations of CD4 and age-related risk of progression to AIDS or death [50]. A %CD4+ of 35 is associated with a 15% risk of progression to AIDS in the next 12 months among children aged three months and an 11% risk among those six months old. The revised WHO classification attempts to better reflect this increased risk in these younger children. Based on reanalysis of the data, the thresholds for severe immunodeficiency in children have been revised [30]. For children in the WHO classification, age-related severe HIV-related immunodeficiency is defined as values at or below age-related CD4 thresholds below which children have a greater than 5% chance of disease progression to severe clinical events (AIDS) or death in the next 12 months. Further research is urgently required to assess the prognostic significance and to ascertain normal and disease-associated CD4 levels among African and Asian children. Note that, among children younger than one year, the immunological categories do not reflect the same level of risk at any given age; thus, a child six months old has a higher risk of progression for any given CD4 count than a child 11 months old. However, to facilitate the scaling up of access to antiretroviral therapy, WHO proposes this simplified harmonized immunological classification system for adults and children. The immune parameters and therefore classification improve with successful antiretroviral therapy. Immune parameters can be used to monitor the response to antiretroviral therapy, and it is hoped that the immunological classification will facilitate this.