Immunological changes in HIV-1 infection include a decrease in CD4+ cells, a transient increase in CD8+ cells, total lymphocytes and inversion of the CD4/CD8 ratio. As HIV infection progresses, the CD4+ cells decline, while the CD8+ cells which may remain at high levels for long periods, eventually decrease but not to baseline levels.
Plasma HIV-1 viral load, CD4+ cell count and CD4 percentage are used to predict the clinical course and response to therapy in HIV infected adults and children. CD4 count is routinely measured in children with HIV-1 infection and used to evaluate the need of initiation of therapy and to monitor clinical progression. Guidelines issued by various organizations provide recommendations on the basis of CD4 count (or CD4% which in children is found to be more accurate) and some also consider the criteria of viral load.
Immunological monitoring in HIV infected children
Assessment of the CD4 count in any child must be in relation to the appropriate count for age. It has been recognized for many years that healthy young children physiologically have higher absolute CD4 counts compared to adults. For children above 5 years of age, absolute CD4+ counts are used in preference to percentages, and the levels are aligned with adult/adolescent cut-offs. For an individual child the CD4 count will vary, and is often depressed with intercurrent infections, therefore this parameter should usually be measured when the child is in a stable clinical condition. The substantial intra- and inter-individual variation in absolute CD4 counts in young children led to the adoption of CD4 percentages as the preferred method of monitoring in pediatric practice. The CD4 percentage varies less with age and other intercurrent factors than the absolute count, but it may be misleading if the child is absolutely lymphopenic.
Table 2 : WHO immunological classification for established HIV infection
HIV-associated immunodeficiency |
Age related CD4 values |
< 11 months (%CD4+) |
12-35 months (%CD4+) |
36-59 months (%CD4+) |
> 5 years (absolute number per mm3 or (CD4+) |
None or 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% |
Viral load and disease progression
The HIV plasma viral load is predictive of mortality in older children. The relative risk of death is 2.1 times greater, if the presenting HIV RNA was > 100,000 copies / ml. HIV viral load is estimated by COBAS Ampiclor system, branched DNA assay, NASBA test and real time RT PCR assay.
References :
- Shah Ira. Correlation of CD4 count, CD4% and HIV viral load with clinical manifestations of HIV in infected Indian children. Ann Trop Paediatr. 2006;26(2):115-119.
- Parikh S, Shah Ira. Short term follow up of HIV-1 infected children without treatment: use of CD4/CD8 ratio as a marker of disease progression. J Trop Pediatr. Advance Access published September 5, 2010
- Antiretroviral therapy for HIV infection in infants and children: Towards universal access. Recommendations for a public health approach. 2010 revision. World Health Organization.
- Tudor-Williams G. Diagnosis, staging & clinical presentation of HIV in children. Classification of HIV Disease. Available from Tr@inforPedHIV 2011