Current WHO advice on the detection of severe immunosuppression in the absence of sophisticated laboratory tests may result in a significant underestimate of the number of people who would benefit from immediate antiretroviral therapy, according to findings from a joint US/Thai study published in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
The study found that using easily accessible laboratory tests alongside the World Health Organization's current recommendation to treat all patients with symptomatic HIV disease significantly improved the ability of doctors to detect patients at high risk of disease progression, without the need for CD4 cell counting.
The problem
Current WHO HIV treatment guidelines for resource-limited settings recommend that anyone with symptomatic HIV disease should receive antiretroviral treatment. However, using clinical criteria alone may cause doctors to neglect the treatment of individuals who are probably at high risk of disease progression – those who have minor symptoms and CD4 cell counts below 200 cells/mm3.
CD4 cell counts are not routinely available in most resource-limited settings because the tests require special laboratory equipment, but total lymphocyte counts can be carried out more easily and provide a fairly reliable surrogate for the CD4 cell count.
However, there is still some disagreement over the total lymphocyte count threshold that should be considered equivalent to a CD4 cell count of 200 cells/mm3.
The US/Thai study
United States and Thai researchers set out to determine whether they could improve upon the current WHO recommendations by looking at data from 519 Thai patients and examining the relationship between CD4 cell counts and total lymphocyte count, haemoglobin (as a measure of anaemia), physical symptoms and body mass index.
Patients in two CD4 cell count groups (< 200 cells/mm3 and <350) were assessed to determine whether the range of other diagnostic criteria also predicted their level of immunosuppression (a measure of sensitivity).
They found that using a total lymphocyte count cutoff of <1500 cells/mm3 detected almost twice as many people (43% of men, 33% of women) who would have been eligible for treatment due to a CD4 cell count below 200 cells/mm3 when compared with the currently recommended cutoff of 1200 cells/mm3 (23% of men, 16% of women). However, using a TLC cutoff of 1500 cells/mm3 still missed 57% of those who would have been eligible for treatment if CD4 cell counting were to be available.
Greater sensitivity could be achieved, the research group reports, by using both total lymphocyte count and haemoglobin levels. Anaemia, coupled with a TLC <2000 cells/mm3, was substantially more sensitive than the current WHO guidelines on initiating therapy for detecting patients with CD4 cell counts below 200 cells/mm3. The most sensitive algorithm of all combined the WHO guideline (symptomatic HIV disease) with anaemia and a total lymphocyte count below 2000 cells/mm3; this algorithm was almost twice as sensitive as the current WHO guideline.
The findings suggest that easily available laboratory tests may help doctors in determining which patients are most urgently in need of antiretroviral therapy, especially in settings where it is not possible to treat every symptomatic patient with antiretroviral therapy immediately.
Costello C et al. Predictors of low CD4 count in resource-limited settings. J Acquir Immune Defic Syndr 39: 242-248, 2005.