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Immune status in adults The normal absolute CD4 count in adolescents and adults ranges from 500 to 1500 cells per mm3 of blood. In general, the CD4 (%CD4+ or absolute count) progressively decreases as HIV disease advances. As in children, individual counts may vary within an individual adult or adolescent and assessing the CD4 count over time is more useful. The CD4 count usually increases in response to effective combination antiretroviral therapy, although this may take many months. The proposed immunological classification outlines four bands of HIVrelated immunodeficiency: no significant immunodeficiency, mild immunodeficiency, advanced immunodeficiency and severe immunodeficiency. The likelihood of disease progression to AIDS or death without ART increases with increasing immunodeficiency (decreasing CD4), opportunistic infections and other HIV related conditions are increasingly likely with CD4 counts below 200 per mm3. Response to ART is affected by the immune stage at which it is started, people commencing ART with advanced immunodeficiency (CD4 >200–350 per mm3 ) appear to have better virological outcomes than those who commence with more severe immunodeficiency. Adults starting ART with CD4 <50 per mm3 have a much greater risk of death. Adults who commence ART with only mild immunodeficiency do not appear to obtain any additional benefits. Revised antiretroviral therapy recommendations reflect this.i Pregnancy does affect the CD4 count although the significance of these changes is not clearly understood, and for practical purposes the immunological classification remains the same. Clinical decision-making Regardless of age or clinical stage CD4 testing is very valuable and should be encouraged. It is useful to guide the decision on initiation of co-trimoxazole and when to start first-line ART or to identify treatment failure and the need to switch to a second-line regimen of ART. Measurement of CD4 can also be used to assess and monitor response to ART. Where clinical and immunological classifications are both available, immune status, reflected by CD4 (%CD4+ or absolute count) is usually more informative. This is reflected in the most up-todate WHO recommendations on ART for infants, children and adults.ii In younger children %CD4+ should be used, and from five years of age the absolute count is preferred. Severe HIV-related disease always requires ART irrespective of whether defined by clinical condition or immune status. Advanced HIV disease based on immune status requires considering ART, especially when disease is advanced as defined clinically. Starting antiretroviral therapy can usually be delayed if the immune status suggests that there is only mild or insignificant immunodeficiency (%CD4+ >30 among children younger than 12 months, >25 among children 12–35 months or >20 in children over 36 months, or CD4 count >350 per mm3 in adults and older children), and the individual is asymptomatic or only has mild symptoms.
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