Use of total lymphocyte count (TLC) for monitoring response to antiretroviral therapy

CD4 cell count and CD4 cell percentage are key markers for determining disease progression and risk for opportunistic infection in HIV-infected patients.

These markers are of greatest use in treating the asymptomatic patient, in whom disease stage is more difficult to assess clinically and for whom laboratory measurements serve as guidelines for the initiation of therapy and opportunistic-infection prophylaxis.

However, providers in resource-constrained settings may not have access to this laboratory measurement or its cost may be prohibitive, resulting in the need for an alternative, surrogate marker. Given the decreasing costs and increased availability of antiretroviral therapy (ART) in the developing world, this is an issue of critical and increasing importance.

A number of previous studies indicate that the total lymphocyte count (TLC) may be useful as a surrogate marker of immune status in certain settings. However, controversy regarding the utility of the TLC remains.

A variety of recent small studies have sought to determine the utility of the TLC in predicting the stage of HIV disease. The majority of these studies indicate a positive correlation between TLC and CD4 cell count, although the specific data on correlation coefficients, sensitivity, specificity, and positive predictive value (PPV) have been mixed. In addition, the patient populations examined, parameters measured, and methods used for statistical analysis vary widely among the different studies.

TLC may have a role both in decisions about the initiation of ART and in the monitoring of immunologic response to ART in resource-constrained settings. There has been a wide range of findings in published studies, many of which have included small numbers of patients.

To summarise, a total of 15,102 patients enrolled in 15 different studies have been followed up to determine the ability of the TLC to predict the CD4 cell count and HIV disease stage. Eleven of these studies (which included a total of 11,713 patients) contained data that, overall, indicated support for the predictive ability of the TLC, whereas four have concluded that the TLC was not a reliable predictor of the CD4 cell count.

In contrast, only three different studies, with a total of more than 440 patients, have attempted to evaluate the use of TLC in monitoring the response to ART. All of these studies have produced data that, overall, support the use of TLC as a surrogate marker for CD4 cell count in monitoring patients receiving ART.

The authors conclude, “More convenient and less expensive technologies are needed as alternatives to currently available CD4 cell assays in resource-limited settings. Political pressure has been successful in reducing the cost of ART, and it needs to be extended to advocacy for reducing the cost of determining HIV disease stage and monitoring therapeutic outcomes.”


Schreibman T, Friedland G. Use of total lymphocyte count for monitoring response to antiretroviral therapy. Clinical Infectious Diseases 38:257-262. January 15, 2004.

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