Limited role in care for total lymphocyte count?

The WHO guidelines for scaling up antiretroviral therapy in resource-limited settings recommend that anyone with clinical AIDS symptoms should initiate therapy, regardless of CD4 count. The guidelines also recommend that therapy be started when CD4 count falls below 200 cells/mm³ (or when CD4 percentage is less than 15%), whether symptoms are present or not. If CD4 count is not practically obtainable, WHO recommends starting therapy when total lymphocyte count (TLC) falls below 1200/mm³ in the presence of symptomatic HIV disease. TLC below 1200 alone, without symptoms, is not considered grounds for starting treatment.

Despite this endorsement, the usefulness of TLC remains ambiguous. The WHO guidelines note that, “While the total lymphocyte count correlates relatively poorly with the CD4 count, in combination with clinical staging it is a useful marker of prognosis and survival.”

Accordingly, WHO includes TLC among its “basic recommended” lab tests (TLC is calculated from a white blood cell count and differential). Due to cost and technical requirements, CD4 counts, typically performed by flow cytometry in central laboratories, are not currently among WHO’s basic recommended tests for resource-limited settings, although the use of alternative, low-cost cell counting technology is strongly encouraged.

There have been efforts to improve the predictive ability of TLC, for example by combining it with changes in haemoglobin, weight, delayed hypersensitivity and symptomology. A number of efforts have been made to validate the diagnostic potential of TLC by retrospectively analysing medical records of large clinical cohorts of HIV-positive people in developed countries to see how well TLC values correlate with standard CD4 counts in predicting disease progression.

Total lymphocyte count as a surrogate for CD4 cell count

A recently reported study of this type comes from the Chelsea and Westminster HIV cohort in London (Sawleshwarka). Patients with CD4 counts and TLC taken within the three months prior to development of an AIDS-defining opportunistic infection (ADOI) or the initiation of prophylaxis for an opportunistic infection (OI) were identified, and the last TLC/CD4 values obtained during that period were analysed. Of 5,774 patients in the cohort, 1,097 were included for analysis. The cut-off for TLC in this cohort, the point of maximum sensitivity and minimal error, was established at 1500 cells/mm³, which corresponds to the canonical CD4 cut-off of 200 cells/mm³, when therapy should always be introduced. This TLC cut-off is somewhat higher than the level recommended by WHO for use in resource-limited settings.

The study reported that having a TLC between 1000 and 1500 predicted that individuals were 40% more likely to develop an ADOI than those with TLC above 1500 (sensitivity = 68.6; specificity = 66.0). This result compares to a 34% greater likelihood of an ADOI being predicted by a CD4 count between 150 and 200 versus one over 200 (sensitivity = 73.8; specificity = 75.6). Furthermore, the