What is T-cell count

T cell count is also called T lymphocyte or CD4 T lymphocytes or CD4 cells (T-helper cells) count. T cell (CD4 cell) count measures the number of these cells in the blood and, in conjunction with an HIV viral load test, help assess the status of the immune system in a person who has been diagnosed with human immunodeficiency virus (HIV) infection. In people with HIV, the T cell count or CD4 count is the most important laboratory indicator of immune function and the strongest predictor of HIV progression. The T cell count (CD4 count) is also used to monitor a person’s response to antiretroviral therapy (ART).

T cells (CD4 cells) are white blood cells that fight infection and play an important role in immune system function. T cells (CD4 cells) are made in the thymus gland and they circulate throughout the body in the blood and lymphatic system.

CD4 cells are so called because they have markers on their surfaces called clusters of differentiation (CD). The CD number identifies the specific type of cell.

CD4 cells are sometimes called T-helper cells. They help to identify, attack, and destroy specific bacteria, fungi, and viruses that cause infections. CD4 cells are a major target for HIV, which binds to the surface of CD4 cells, enters them, and either replicates immediately, killing the cells in the process, or remains in a resting state, replicating later.

If HIV goes untreated, the virus gets into the cells and replicates, the viral load increases, and the number of CD4 cells in the blood gradually declines. The T cell (CD4 cell) count decreases as the disease progresses. If still untreated, this process may continue for several years until the number of CD4 cells drops to a low enough level that symptoms associated with AIDS begin to appear.

Treatment for HIV infection, called antiretroviral treatment (ART or ARV) or sometimes highly active antiretroviral therapy (HAART), typically involves taking a combination of drugs. This treatment reduces the amount of HIV (viral load) present in the body and reduces the risk of disease progression. When this occurs, the CD4 count will increase and/or stabilize.

CD8 cells are another type of lymphocyte. They are sometimes called T-suppressor cells or cytotoxic T cells. CD8 cells identify and kill cells that have been infected with viruses or that have been affected by cancer. They play an important role in the immune response to HIV infection by killing cells infected with the virus and by producing substances that block HIV replication.

As HIV disease progresses, the number of CD4 cells will decrease in relation to the number of total lymphocytes and CD8 cells. To provide a clearer picture of the condition of the immune system, test results may be reported as a ratio of CD4 to total lymphocytes (percentage).

CD4 and CD8 tests may be used occasionally in other conditions, such as lymphomas, organ transplantation and DiGeorge syndrome. CD8 cells are another type of lymphocyte that identify and kill cells that have been infected with viruses or that have been affected by cancer.

Use of CD4 Count for Initial Assessment

The CD4 count is one of the most important factors in determining the urgency of antiretroviral treatment (ART) initiation and the need for prophylaxis for opportunistic infections. All patients at entry into care should have a baseline CD4 count.

Use of CD4 Count for Monitoring Therapeutic Response

An adequate CD4 response for most patients on therapy is defined as an increase in CD4 count in the range of 50 to 150 cells/mm³ per year, generally with an accelerated response in the first 3 months of treatment. Subsequent increases in patients with good virologic control average approximately 50 to 100 cells/mm³ per year until a steady state level is reached ¹. Patients who initiate therapy with a low CD4 count ² or at an older age ³ may have a blunted increase in their counts despite virologic suppression.

Frequency of CD4 Count Monitoring

ART now is recommended for all HIV-infected patients. In untreated patients, CD4 counts should be monitored every 3 to 6 months to determine the urgency of ART initiation. In patients on ART, the CD4 count is used to assess the immunologic response to ART and the need for initiation or discontinuation of prophylaxis for opportunistic infections.

The CD4 count response to ART varies widely, but a poor CD4 response is rarely an indication for modifying a virologically suppressive antiretroviral (ARV) regimen. In patients with consistently suppressed viral loads who have already experienced ART-related immune reconstitution, the CD4 cell count provides limited information, and frequent testing may cause unnecessary anxiety in patients with clinically inconsequential fluctuations. Thus, for the patient on a suppressive regimen whose CD4 cell count has increased well above the threshold for opportunistic infection risk, the CD4 count can be measured less frequently than the viral load. In such patients, CD4 count may be monitored every 6 to 12 months, unless there are changes in the patient’s clinical status, such as new HIV-associated clinical symptoms or initiation of treatment with interferon, corticosteroids, or anti-neoplastic agents

Factors that affect absolute CD4 count

The absolute CD4 count is a calculated value based on the total white blood cell (WBC) count and the percentages of total and CD4+ T lymphocytes. This absolute number may fluctuate in individuals or may be influenced by factors that may affect the total WBC count and lymphocyte percentages, such as use of bone marrow-suppressive medications or the presence of acute infections. Splenectomy ⁴ or co-infection with human T-lymphotropic virus type I (HTLV-1) ⁵ may cause misleadingly elevated absolute CD4 counts. Alpha-interferon, on the other hand, may reduce the absolute CD4 count without changing the CD4 percentage ⁶. In all these cases, CD4 percentage remains stable and may be a more appropriate parameter to assess the patient’s immune function.

When is T-cell count ordered?

A CD4 count is usually ordered along with an HIV viral load when a person is first diagnosed with HIV infection as part of a baseline measurement. After the baseline, a CD4 count will usually be ordered at intervals over time, depending on a few different factors.

The following table summarizes recommendations for the timing of CD4 counts and viral load testing:

What is a normal T-cell count?

A T cell (CD4 cell) count is typically reported as an absolute level or count of cells (expressed as cells per cubic millimeter of blood). The normal T cell (CD4 cell) count range is between 500 – 1400 cells/microliters (500–1,400 cells/mm³) in adults and teens, taking into consideration laboratory variations.

Sometimes results are expressed as a percent of total lymphocytes (CD4 percent).

In general, a normal CD4 count means that the person’s immune system is not yet affected by HIV infection. A low CD4 count indicates that the person’s immune system has been affected by HIV and/or the disease is progressing. However, any single CD4 test result may differ from the last one even though the person’s health status has not changed. Usually, a health practitioner will take several CD4 test results into account rather than a single value and will evaluate the pattern of CD4 counts over time.

CD4 counts that rise and/or stabilize over time may indicate that the person is responding to treatment. If someone’s CD4 count declines over several months, a health practitioner may recommend starting prophylactic treatment for opportunistic infections such as Pneumocystis carinii (jiroveci) pneumonia (PCP) or candidiasis (thrush).

Low T-cell count

CD4 cells are the main target of HIV. The virus enters the cells and uses them to make copies of itself (replicate) and spread throughout the body. HIV kills CD4 cells, so if an HIV infection is not treated, the number of CD4 cells will decrease as HIV infection progresses.

It is recommended that all individuals diagnosed with HIV infection receive antiretroviral treatment (ART) as soon as possible, including pregnant women, to reduce the risk of disease progression. People typically take at least three drugs from two different classes in order to prevent or minimize virus replication and the emergence of drug-resistant strains. Combinations of three or more antiretroviral drugs are referred to as highly active antiretroviral therapy or HAART.

Since CD4 cells are usually destroyed more rapidly than other types of lymphocytes and because absolute counts can vary from day to day, it is sometimes useful to look at the number of CD4 cells compared to the total lymphocyte count. The result is expressed as a percentage, i.e., CD4 percent.

The results can tell a health practitioner how strong a person’s immune system is and can help predict the risk of complications and debilitating opportunistic infections. CD4 counts are most useful when they are compared with results obtained from earlier tests. They are used in combination with the HIV viral load test, which measures the amount of HIV in the blood, to monitor how effective ART is in suppressing the virus and determine the risk of progression of HIV disease.

Low T-cell count causes

Lower than normal T-cell levels may be due to:

• Acute viral infections
• Aging
• Cancer
• Immune system diseases, such as HIV/AIDS
• Radiation therapy
• Steroid treatment

CD4 cells are the main target of HIV. The virus enters the cells and uses them to make copies of itself (replicate) and spread throughout the body. HIV kills CD4 cells, so if an HIV infection is not treated, the number of CD4 cells will decrease as HIV infection progresses.

The CD4 count also tends to be lower in the morning and higher in the evening. Acute illnesses, such as pneumonia, influenza, or herpes simplex virus infection, can cause the CD4 count to decline temporarily. Cancer chemotherapy can dramatically lower the CD4 count.

Low T-cell count symptoms

The CD4 count does not always reflect how someone with HIV disease feels and functions. For example, some people with higher counts are ill and have frequent complications, and some people with lower CD4 counts have few medical complications and function well.

The symptoms of HIV vary, depending on the phase of infection.

Primary infection (Acute HIV)

Most people infected by HIV develop a flu-like illness within a month or two after the virus enters the body. This illness, known as primary or acute HIV infection, may last for a few weeks. Possible signs and symptoms include:

• Fever
• Headache
• Muscle aches and joint pain
• Rash
• Sore throat and painful mouth sores
• Swollen lymph glands, mainly on the neck

These symptoms can be so mild that you might not even notice them. However, the amount of virus in your bloodstream (viral load) is quite high at this time. As a result, the infection spreads more easily during primary infection than during the next stage.

Clinical latent infection (Chronic HIV)

In some people, persistent swelling of lymph nodes occurs during this stage. Otherwise, there are no specific signs and symptoms. HIV remains in the body and in infected white blood cells.

This stage of HIV infection generally lasts around 10 years if you’re not receiving antiretroviral therapy. But sometimes, even with this treatment, it lasts for decades. Some people develop more severe disease much sooner.

Symptomatic HIV infection

As the virus continues to multiply and destroy your immune cells — the cells in your body that help fight off germs — you may develop mild infections or chronic signs and symptoms such as:

• Fever
• Fatigue
• Swollen lymph nodes — often one of the first signs of HIV infection
• Diarrhea
• Weight loss
• Oral yeast infection (thrush)
• Shingles (herpes zoster)

HIV infection weakens your immune system, making you much more likely to develop numerous infections and certain types of cancers.

Infections common to HIV/AIDS

• Tuberculosis (TB). In resource-limited nations, TB is the most common opportunistic infection associated with HIV. It’s a leading cause of death among people with AIDS.
• Cytomegalovirus. This common herpes virus is transmitted in body fluids such as saliva, blood, urine, semen and breast milk. A healthy immune system inactivates the virus, and it remains dormant in your body. If your immune system weakens, the virus resurfaces — causing damage to your eyes, digestive tract, lungs or other organs.
• Candidiasis. Candidiasis is a common HIV-related infection. It causes inflammation and a thick, white coating on the mucous membranes of your mouth, tongue, esophagus or vagina.
• Cryptococcal meningitis. Meningitis is an inflammation of the membranes and fluid surrounding your brain and spinal cord (meninges). Cryptococcal meningitis is a common central nervous system infection associated with HIV, caused by a fungus found in soil.
• Toxoplasmosis. This potentially deadly infection is caused by Toxoplasma gondii, a parasite spread primarily by cats. Infected cats pass the parasites in their stools, which may then spread to other animals and humans. Seizures occur when it spreads to the brain.
• Cryptosporidiosis. This infection is caused by an intestinal parasite that’s commonly found in animals. You get it when you eat or drink contaminated food or water. The parasite grows in your intestines and bile ducts, leading to severe, chronic diarrhea in people with AIDS.

Cancers common to HIV/AIDS

• Kaposi’s sarcoma. A tumor of the blood vessel walls, this cancer is rare in people not infected with HIV, but common in HIV-positive people. It usually appears as pink, red or purple lesions on the skin and mouth. In people with darker skin, the lesions may look dark brown or black. Kaposi’s sarcoma can also affect the internal organs, including the digestive tract and lungs.
• Lymphoma. This cancer starts in the white blood cells. The most common early sign is painless swelling of the lymph nodes in your neck, armpit or groin.

Other complications

• Wasting syndrome. Aggressive treatment approaches have reduced the number of cases of wasting syndrome, but it still affects many people with AIDS. It’s defined as a loss of at least 10 percent of body weight, often accompanied by diarrhea, chronic weakness and fever.
• Neurological complications. Although AIDS doesn’t appear to infect the nerve cells, it can cause neurological symptoms such as confusion, forgetfulness, depression, anxiety and difficulty walking. One of the most common neurological complications is AIDS dementia complex, which leads to behavioral changes and reduced mental functioning.
• Kidney disease. HIV-associated nephropathy (HIVAN) is an inflammation of the tiny filters in your kidneys that remove excess fluid and wastes from your blood and pass them to your urine. It most often affects blacks or Hispanics. Anyone with this complication should be started on antiretroviral therapy.

T-cell count in HIV

Patients with HIV and a CD4 counts greater than 200 cells/mm³, but less than 500 cells/mm³ do not have AIDS but can develop chronic infections as well as noninfectious conditions. Diseases such as chronic candidiasis of the mouth or recurrent vaginal candida may occur. Patients may develop severe bouts of herpes simplex or herpes zoster (shingles). Patients are also at a higher risk for cancers that are much more difficult to treat than in healthy people. Patients with normal CD4 counts (greater than 500) tend to have a good quality of life with a lifespan within 4 years of someone without HIV Patients with a CD4 count less than 200 have AIDS and are susceptible to opportunistic infections. They usually have a lifespan of 2 years if they are started on HAART. If these patients are treated with antiretroviral agents and achieve a CD4 count greater than 500 cells/mm³, they will have a normal life expectancy.

The prognosis of a patient with HIV and a CD4 count greater than 500 cells/mm³ (normal) results in a life expectancy as someone without HIV ⁷.

How does HIV become AIDS?

HIV destroys CD4 T cells — white blood cells that play a large role in helping your body fight disease. The fewer CD4 T cells you have, the weaker your immune system becomes.

You can have an HIV infection for years before it turns into AIDS. AIDS is diagnosed when the CD4 T cell count falls below 200 cells/mm³ or you have an AIDS-defining complication.

AIDS T-cell count

The Centers for Disease Control and Prevention (CDC) considers people who have an HIV infection and CD4 counts below 200 cells/mm³ to have AIDS (stage III HIV infection), regardless of whether they have any signs or symptoms.

Thanks to better antiviral treatments, most people with HIV in the U.S. today don’t develop AIDS. Untreated, HIV typically turns into AIDS in about 10 years.

When AIDS occurs, your immune system has been severely damaged. You’ll be more likely to develop opportunistic infections or opportunistic cancers — diseases that wouldn’t usually trouble a person with a healthy immune system.

The signs and symptoms of some of these infections may include:

• Soaking night sweats
• Recurring fever
• Chronic diarrhea
• Persistent white spots or unusual lesions on your tongue or in your mouth
• Persistent, unexplained fatigue
• Weight loss
• Skin rashes or bumps

A person with untreated AIDS has a life expectancy of about 1 to 2 years after the first opportunistic infection. Antiretroviral treatment can increase CD4 counts and change the patient’s status from AIDS to someone with HIV ⁷.

High T-cell count

Higher than normal T-cell levels may be due to:

• Cancer, such as acute lymphocytic leukemia or multiple myeloma
• Infections, such as hepatitis or mononucleosis

1. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: The Swiss HIV Cohort Study. Arch Intern Med. Oct 13 2003;163(18):2187-2195.[↩]
2. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. Feb 1 2007;44(3):441-446[↩]
3. Althoff KN, Justice AC, Gange SJ, et al. Virologic and immunologic response to HAART, by age and regimen class. AIDS. Oct 23 2010;24(16):2469-2479[↩]
4. Bernard NF, Chernoff DN, Tsoukas CM. Effect of splenectomy on T-cell subsets and plasma HIV viral titers in HIV-infected patients. J Hum Virol. Jul-Aug 1998;1(5):338-345[↩]
5. Casseb J, Posada-Vergara MP, Montanheiro P, et al. T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1): High prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Rev Inst Med Trop Sao Paulo. Jul-Aug 2007;49(4):231-233[↩]
6. Berglund O, Engman K, Ehrnst A, et al. Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine. J Infect Dis. Apr 1991;163(4):710-715[↩]
7. Justiz Vaillant AA, Gulick PG. HIV Disease. [Updated 2019 Feb 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534860[↩][↩]