How Important Is Your CD4/CD8 Ratio?

Relevance of Prognostic Tests Varies by Setting and Population

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The CD4/CD8 ratio is a prognostic assessment of a person's immune system, comparing the proportion of "helper" CD4 T-cells to that of "suppressor" CD8 T-cells. A prognostic evaluation is one meant to determine the likely course of a disease, as when a person is infected with HIV.

Understanding How CD4 and CD8 T-Cells Interact

CD4 and CD8 are simply two different types of glycoprotein found on the surface of T-cells and other lymphocytes (the class of white blood cells central to the immune system). CD4 T-cells are considered "helpers" because they’re the ones that trigger an immune response when faced with a pathogen (infective agent).

When this occurs, CD8 "suppressor" T-cells are activated to attack and kill those pathogens. They then act by shutting off CD4 activity when a sufficient immune response has been achieved.

A CD4/CD8 ratio is considered normal when it is between 1.0 and 4.0. In a healthy individual that translates to between 30-60% CD4 T-cells and 10-30% CD8 T-cells.

However, when a person is first infected with HIV, there is generally a 30% drop in the number of CD4 T-cells as HIV targets these cells and depletes their numbers. By contrast, of CD8 T-cells will generally increase by about 40% during, although their ability to neutralize the virus will wane over time as there are simply fewer CD4 T-cells to trigger an effective response.

When antiretroviral therapy (ART) is initiated in a timely manner in a person with HIV, the ratio generally returns to normal. However, if treatment is delayed, the body's ability to reconstitute CD4 T-cells weakens, and the ratio often remains below 1.0.

What the CD4/CD8 Ratio Tells Us

The prognostic value of CD4/CD8 is considered less relevant to the management of HIV than it was 20 years ago, when there were fewer, less effective antiretrovirals available to treat HIV. While it can be indicative of the age of the infection and predictive of AIDS-related mortality, greater emphasis today is placed on sustaining viral suppression (as measured by a person's viral load) in order to slow disease progression and avoid the development of HIV drug resistance.

With that being said, increasing focus is being placed on the CD4/CD8 dynamic in aging HIV population. Recent clinical studies have suggested that patients on effective, long term ART with a low CD4/CD8 ratio have an increased risk of non-HIV-related morbidity and mortality.

There are a number of other areas where the CD4/CD8 ratio may also be pertinent. In epidemiological research, it can be used as a value by which to measure the virulence (i.e., the ability of a pathogen to cause disease) of HIV in different populations or over a period of time.

It can be used to predict the likelihood of IRIS (immune reconstitution inflammatory syndrome) that can sometimes occur when a person initiates antiretroviral therapy. If the baseline CD4 counts is low and is accompanied with a low CD4/CD8 ratio is well below 0.20, the chances of an IRIS event increases significantly.

Similarly, research has suggested that a low CD4/CD8 count in infants born to HIV-positive mothers is predictive of whether that child will seroconvert (be confirmed HIV-positive), with the likelihood increasing dramatically when the ratio is below 1.0. This may be particularly relevant in developing countries where the number of mother-to-child transmissions have dramatically decreased but the number of HIV-infected children on ART remains high.

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  • Mahnke, Y.; Greenwald, J.; DerSimonian, R.; et al. "Selective expansion of polyfunctional pathogen-specific CD4 Tcells in HIV-1–infected patients with immune reconstitution inflammatory syndrome." Blood. March 29, 2012; 119(13):3105-3112.
  • Zijenah, L.; Katzenstein, D.; Nathoo, K.; et al. "T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years." Journal of Translational Medicine. 1 February 2005; 3:6: doi:10.1186/1479-5876-3-6.
  • Seng, R.; Goujard, C.; Krastinova, E.; et al. "Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy." AIDS. January 13, 2015; published ahead of print; DOI: 10.1097/QAD.0000000000000571.