What Is a CD4/CD8 Ratio?

The CD4/CD8 ratio is one of the blood tests used to monitor your immune system if you have human immunodeficiency virus (HIV). It compares the proportion of so-called "helper" CD4 T cells to "killer" CD8 T cells, the value of which can help predict the likely course of the disease.

T cells are a type of white blood cell that is central to your immune defense. There are four types which serve different functions:

• CD8 T cells are considered "killers" because their function is to destroy any cells in the body that harbor a virus, bacteria, or other disease-causing agents (pathogens).
• CD4 T cells are considered "helpers" because they start up the immune response.
• Suppressor T cells are responsible for turning off the immune response when a threat has been neutralized.
• Memory T cells remain on sentinel once a threat has been neutralized and "sound off the alarm" if the threat ever returns.

Of these four types, CD4 and CD8 T cells are routinely used to monitor HIV infection, either alone or in comparison to each other.

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 work by triggering an immune response when faced with a pathogen. CD8 T cells respond by attacking the tagged pathogen and neutralizing it. Suppressor T cells then "turn off" CD4 activity when a sufficient immune response has been achieved.

A CD4/CD8 ratio is considered normal when the value is between 1.0 and 4.0. In a healthy individual, that translates to roughly 30%–60% CD4 T cells in relationship to 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, CD8 T cells will generally increase by about 40%, 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 HIV therapy is initiated in a timely manner, the ratio will generally return to normal. However, if the treatment is delayed until the immune system is seriously damaged, the body's ability to create new CD4 T cells will weaken. If this happens, the ratio may never rise much above 1.0.

What the CD4/CD8 Ratio Tells Us

The prognostic (predictive) 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 drugs available to treat HIV. While the value can still help us determine the age of the infection and your risk of mortality, greater emphasis has been placed in recent years on sustaining viral control (as measured by an undetectable viral load). Doing so helps slow disease progression and avoid the development of drug resistance, when a drug no longer works.

With that being said, increasing focus has been placed on the use of CD4/CD8 ratio in people with long-term HIV infection. Recent studies have suggested that people with a low CD4/CD8 ratio who have been on treatment for years are at an increased risk of non-HIV-related illness and death.

There are a number of other areas in which the CD4/CD8 ratio may also be important. In epidemiological research, the ratio can be used to measure virulence (the ability to cause disease) of HIV in different populations or over specific periods of time.

It can also be used to predict the likelihood of immune reconstitution inflammatory syndrome (IRIS), a serious reaction that can sometimes occur when a person starts HIV therapy. If the baseline CD4 count is low and is accompanied by a CD4/CD8 ratio below 0.20, the risk of IRIS increases significantly.

Similarly, research has shown that a low CD4/CD8 count in babies born to HIV-positive mothers can be used to predict whether that baby will seroconvert (become HIV-positive too).The likelihood of this increases dramatically when the ratio falls below 1.0. This may be especially relevant in developing countries where the rate of mother-to-child transmissions has dropped but the number of postnatal seroconversions remains high.

How Often to Get Tested

For people newly diagnosed with HIV, routine blood monitoring should be performed at the time of entry into care and then every three to six months afterward. This includes the CD4 count and viral load. Once you have been on treatment and have maintained an undetectable viral load for a least two years:

• CD4 monitoring can be performed every 12 months for people whose CD4 count is between 300 and 500.
• CD4 monitoring may be considered optional for those with CD4 counts over 500.