Example: Intermediate Variable - HIV CCR5

Lead Author(s): Jeff Martin, MD

CCR5 Receptor on the CD4 Cells

Taylor published findings on the human cellular receptor for HIV, the CCR5 receptor on CD4 cells. We know that CD4 count is a potent predictor of time-to-AIDS.

How should CD4 count be handled in assessing the association between CCR5 defect status and progression in HIV disease to AIDS?


Assessing Role of CCR5 - What Is Your Research Question?

To determine if CD4 count is an intermediary variable we ask: To determine if CD4 count is a confounding variable we ask:

Intermediary Variable: Not Adjusting to Answer Your Research Question

If your research question was: Is CCR5 associated with progression to AIDS, irrespective of mechanism?


We are asking the question as to whether CCR5 defect status is associated with time to AIDS. IN THIS CASE, DO NOT ADJUST OR CONTROL FOR CD4 COUNT When CD4 count was treated as an intermediary variable and not adjusted for, an association was seen.

Confounding Variable: Adjusting to Answer Your Research Question

If your research question is: Is CCR5 asssocated with progression to AIDS, *independent of CD4 count*?


You can see that if you had blithely adjusted for the CD4 count first, Hence, you need always need to keep in mind exactly what the research question is and whether or not adjustment is needed to answer it.


Taylor, J. M., Wang, Y., Ahdieh, L., Chmiel, J. S., Detels, R., Giorgi, J. V., et al. (2000). Causal pathways for CCR5 genotype and HIV progression. J Acquir Immune Defic Syndr, 23(2), 160-171.