A total lymphocyte count and serum albumin levels may predict disease progression in HIV-positive children where CD4 and viral load testing are not affordable, according to US research published today in The Lancet.
Lynne Mofenson from the US National Institutes of Health, and colleagues assessed the prognostic value of five measures (total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume, and blood albumin) for death in 376 HIV-1-infected children. The investigators found that total lymphocyte count and albumin independently predicted the risk of death in HIV-1-infected children of all ages.
The researchers found that the 12-month risk of death in children below the age of 2 was greater than 15% when the total lymphocyte count was less than 3,600 cells/ mm3, whilst in children aged 2 years old or above, the 12 month risk of death was greater than 15% when the total lymphocyte count was less than 2,300 cells/mm3.
For albumin, the 12 month risk of death was greater than 15% when the albumin concentration fell below 3.7 – 4.0 g/dL.
Of note, p24 antigen was not predictive, adding further weight to the view that p24 antigen will not prove to be a useful surrogate for viral load in resource limited settings.
"Use of one or more of these assays could serve as relatively inexpensive means to establish when to initiate antiretroviral therapy in children in settings where CD4 and RNA assays are not available”, said Lynn Mofenson. “Total lymphocyte count remained predictive even when CD4 and RNA values were known."
A potential weakness of this study is that it was carried out in North American infants prior to the introduction of HAART. Different background patterns of nutrition and illness may lead to differing total lymphocyte values being predictive of disease progression in different populations.
Draft World Health Organisation guidelines recommend that in resource limited settings, a total lympocyte count below 2,500mm3 should be taken into consideration when assessing children below the age of 18 months with mildly symptomatic HIV disease (WHO Stage II disease) for antiretroviral treatment.
In adults, total lymphocyte count is a weak surrogate for the CD4 cell count in the absence of symptoms, and cannot be used to monitor responses to therapy.
In an accompanying Commentary in this week’s Lancet, François Dabis from INSERM, France, concludes: "The urgency now is to start HAART in as many African HIV-infected children as possible because the disease burden is unacceptable. Children born to HIV-infected mothers who fail one of the interventions for peripartum mother-to-child transmission of HIV are an obvious target, assuming early diagnosis of paediatric HIV is widely implemented with the same low-cost technologies. Older children in the same families should also be offered diagnosis and treatment. Children's clinics could be another portal of entry for proposing HIV screening and starting treatment to more children. Finally, we should not forget that many HIV-infected children are particularly vulnerable and in need of treatment are orphaned. Reducing the proportion of infants infected by HIV by 20% by 2005 is not an easy target set by WHO, and requires that all solutions are implemented at the same time. Antiretroviral therapy of children is now clearly one of them for Africa."
Further information on this website
Monitoring the immune system in resource-limited settings
References
Dabis F et al. Children and HIV in Africa: what is next? The Lancet 362: 1597—98, 2003.
Mofenson LM et al. Altenatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1 infected children in resource-limited settings. The Lancet 362: 1625-27, 2003.