Stage of AIDS how many CD4 cells. What are CD4 cells? The decision to start antiretroviral therapy

There are two very important tests that all people with HIV need - immune status and viral load. Sometimes their meanings can be difficult to understand. At the same time, it is thanks to them that it is possible to determine the moment to start treatment and the effectiveness of the drugs. This article describes basic information about these tests that cannot replace a conversation with your doctor, but can help facilitate the dialogue between the doctor and the patient.
What is immune status?
Immune status determines the number of different cells of the immune system. For people with HIV, what matters is the number of CD4 cells or T-lymphocytes - white blood cells that are responsible for “recognizing” various pathogenic bacteria, viruses and fungi that must be destroyed by the immune system.
CD4 cell count is measured as the number of CD4 cells per milliliter of blood (not the whole body). It is usually written as cells/ml. The CD4 cell count of an HIV-negative adult is usually somewhere between 500 and 1200 cells/mL. HIV can infect CD4s and make copies of itself in them, causing the cells to die. Although cells are killed by HIV every day, millions of CD4 cells are produced to replace them. However, over a long period of time, the CD4 count can decrease and even drop to dangerous levels.
What does the CD4 count tell you?
For most people with HIV, their CD4 count usually declines over a period of years. A CD4 count between 200 and 500 indicates a weakened immune system. If your CD4 count falls below 350 or begins to decline rapidly, this is a reason to talk to your doctor about prescribing antiretroviral therapy.
If the CD4 cell count is 200-250 cells/ml or lower, initiation of therapy is recommended, since with such an immune status there is a risk of AIDS-associated diseases. The main thing that the CD4 count tells us is the health of the immune system, whether it is worsening or improving.
Changes in CD4 count
Your CD4 cell count can rise and fall as a result of infections, stress, smoking, exercise, your menstrual cycle, birth control pills, the time of day, and even the time of year. Moreover, different test systems may give different CD4 count results.
That is why it is very important to regularly get tested for your immune status and look at changes in the results. It is impossible to assess the health status of an HIV-positive person with one single test. It is also best to measure your CD4 count in the same clinic, around the same time of day. If you have an infection, such as a cold or herpes, it is best to delay getting tested until your symptoms have gone away.
If you have a relatively high CD4 cell count, no symptoms, and are not taking antiretroviral therapy, getting your immune status tested every 3 to 6 months is sufficient. However, if your immune status is rapidly declining or you start taking medications, your doctor should suggest you get tested more often.
If your CD4 cell count varies greatly from time to time, your total white blood cell count may be changing, possibly due to an infection. In this case, the doctor will pay attention to other indicators of immune status. For example, the CD4/CD8 ratio.
CD8 are other cells of the immune system that are not affected by HIV. On the contrary, with the development of HIV infection, their number does not decrease, but increases, as the body’s reaction to the infection. Normally, the number of CD4 and CD8 is approximately equal, but as the disease progresses, the CD4/CD8 ratio decreases. However, if a person has a normal CD4 cell count, the CD8 count does not matter much.
The CD4 percentage also indicates the true state of the immune system.
CD4 percentage
Instead of counting the number of CD4 per milliliter, your doctor can estimate the percentage that CD4 make up of the total number of white cells. This is the percentage of CD4 cells. Normally it is about 40%. A CD4 percentage of less than 20% is about the same as a CD4 count of less than 200 cells/mL.
A viral load test determines the number of virus particles in a fluid, more precisely in blood plasma. This test only detects HIV genes, that is, the RNA of the virus. The viral load result is measured in the number of copies of HIV RNA per milliliter. Viral load is a "predictive" test. It shows how quickly a person's immune status can decrease in the near future.
If we compare the development of HIV infection with a train that goes to its destination (AIDS-associated diseases), then the immune status is the distance that remains, and the viral load is the speed at which the train is moving.
Currently, different types of viral load tests are used. Each test system is a different technique for detecting viral particles, so it will depend on the test system whether the result is considered low, medium or high. Nowadays, viral load tests are reliable for any subtype of the virus.
Natural variations
Viral load levels may rise or fall, but this does not affect a person's health. Research shows that for people not taking antiretroviral therapy, two viral load tests from the same blood sample can differ by up to three times. In other words, you don't necessarily need to worry if your viral load rises from 5,000 to 15,000 copies/ml if you don't take treatment. Even a twofold increase may turn out to be a simple error in the test system.
Ideally, you should test your viral load when you are healthy. If you have had an infection or have recently been vaccinated, your viral load may temporarily increase.
Significant changes
There is cause for concern only when the viral load test result remains elevated for several months, or if the viral load has more than tripled. For example, if the viral load increased from 5,000 to 25,000 copies/ml, this is a significant change, since the result has increased fivefold. However, it is still best to re-test to confirm the trend of increasing viral load.
Effect of vaccinations and infections
If you have recently had an infection or been vaccinated, you may experience a temporary increase in your viral load. In these cases, it is recommended to postpone the viral load test for at least a month after vaccination or illness.
Minimizing deviations
Information about changes in viral load will be more reliable if the tests are done in the same clinic using the same method. If this is your first time taking a viral load test, try to remember the method that was used for it. When you take a viral load test in the future (especially if you take it at another hospital), make sure that the same method that was used to determine your load will be used.
If you are not taking antiretroviral therapy
If you are not taking antiretroviral therapy, your viral load can predict whether you will develop HIV infection without taking therapy.
Findings from a study examining changes in viral load in people not taking antiretroviral therapy suggest that, when combined with CD4 cell count, viral load may predict the risk of developing symptoms in the future. In people with the same CD4 cell count, the researchers found that those with higher viral loads tended to develop symptoms more quickly than those with low viral loads. Among a group of people with the same viral load, symptoms developed more often in those who had lower immune status.
Taken together, CD4 cell count and viral load provide a basis for predicting the development of HIV infection in the short and medium term.
The decision to start antiretroviral therapy
Your viral load level, along with other indicators, can help you decide whether to start treatment or not.
There are currently guidelines to guide clinicians when deciding when to initiate antiretroviral therapy, with CD4 cell count playing a larger role than viral load. It is recommended to start therapy before the immune status drops to 200 cells. In people with higher immune status, the decision to prescribe therapy may depend on the level of viral load, the rate of decline in immune status, the likelihood of strict adherence to therapy, the presence of symptoms, and the wishes of the patients themselves.
People who have been advised to start antiretroviral therapy but decide to defer it should monitor their immune status and viral load more regularly and consider taking it again.
If we compare the same indicators of immune status in women and men, then in women, on average, the immune status begins to decline with a lower viral load. However, this does not in any way affect the body's response to antiretroviral therapy.
What does an undetectable viral load mean?
All tests that measure viral load have a sensitivity threshold below which they cannot detect HIV. It may be different in different test systems. However, the fact that the viral load is not detectable does not mean that the virus has completely disappeared from the body. The virus is still present in the body, but in such small quantities that the test has difficulty detecting it. Viral load tests only measure the amount of virus in the blood. Even if you have an undetectable viral load, this does not mean that it is also undetectable in other parts of the body, such as in semen.
What is the detection threshold for current tests?
Test systems used in most hospitals in Russia determine the amount of virus up to 400-500 copies/ml. Some modern hospitals use more sensitive tests that detect up to 50 copies/ml. A test system has already been developed that determines the level of the virus in the blood up to 2 copies/ml, but it is not yet used anywhere.
What are the benefits of having an undetectable viral load?
It is desirable to have an undetectable viral load for two reasons:
- very low risk of progression of HIV infection
- very low risk of developing resistance to antiretroviral drugs taken.
It is precisely in reducing the viral load to an undetectable level that the purpose of antiretroviral therapy lies, according to doctors. For some people, it may take 3 to 6 months for the viral load to decrease to an undetectable level, for some it takes 4-12 weeks, and for others the load may not decrease to an undetectable level. People taking antiretroviral therapy for the first time are more likely to have their viral load reduced to undetectable levels than those who have already taken it. Doctors usually recommend changing the combination of drugs or changing one of the drugs if the viral load does not decrease to undetectable levels after 3 months of treatment.
However, doctors have different opinions about how quickly medications should be changed. Some believe that the sooner you change drugs, the lower the risk of developing resistance. Others feel that this may cause them to stop taking therapies that are effective for them. When changing your therapy regimen, you should be prescribed drugs that you have not taken before and that do not belong to the same class. The more drugs you change, the more problems with resistance may arise.
The faster your viral load drops to undetectable levels, the longer it will remain undetectable if you strictly adhere to your medication regimen. After 6 months of therapy without changing medications, ideally the viral load should decrease to an undetectable level. But this is not a mandatory condition, although desirable. It's important to remember that even if your viral load has dropped to 5,000 copies, your risk of developing AIDS-related illnesses is very low if your viral load remains at that level.
If you have a high viral load in your blood, you may also have a high viral load in your semen or vaginal secretions. The higher the viral load, the higher the risk of HIV transmission may be. Antiretroviral therapy that reduces the viral load in the blood usually also reduces the level of virus in semen and vaginal secretions. However, if your viral load in your blood drops to undetectable levels after taking therapy, this does not mean there is no longer virus in your semen or vaginal secretions. However, the risk of HIV transmission during unprotected sex exists, although it decreases with a low viral load. If you have other untreated sexually transmitted infections, especially gonorrhea, they can increase the viral load of semen and vaginal secretions, thereby increasing the risk of HIV transmission through unprotected contact.
Antiretroviral therapy has been shown to be effective in reducing the risk of mother-to-child transmission of the virus. If you are pregnant or planning to become pregnant, be sure to discuss your medication choices with your healthcare provider. If you have an undetectable viral load during pregnancy, the risk of passing HIV to your baby will be very low.
If you are not taking therapy
There is a significant difference in the progression of HIV infection when comparing viral loads below 5000 copies and above 50,000 copies/ml, even if the immune status is above 500 cells.
If the immune status is in the range of 350-200 cells and is rapidly declining, you should see a doctor every month or, if possible, every week, since with a sharp decrease in immune status there is a risk of developing AIDS-related diseases.
If your immune status is above 500 cells, it is advisable to visit your doctor to measure your viral load every 4-6 months.
If your viral load increases while on therapy
It is necessary to repeat the viral load test after 2-4 weeks to confirm the first result. It is advisable to take tests for viral load and immune status always at the same time.
Edited by Misima (02/09/2008 08:16:21 PM)

CD4 count(full name: CD4+ T-cell count, or CD4+ T-cell count, or T4, or immune status) is a blood test result that shows how many of these cells are contained in a cubic millimeter of blood.

The CD4 count is a very good surrogate marker. It indicates how strongly HIV has affected the immune system, what is the depth of the infectious process, what is the risk of other infections, when it is necessary to start treatment. The average CD4 cell count for an HIV-negative person ranges from 600 to 1900 cells/ml of blood, although some people may have higher or lower levels.

2-3 weeks after infection, the CD4 count usually falls.

As the immune system begins to fight back, the CD4 count rises again, although not to baseline levels.

Over the years, the CD4 count gradually decreases. The average annual decline in CD4 count is about 50 cells/mm3. For each individual person, this rate is individual, depends on many factors, such as the subtype of the virus, the person’s age, the route of HIV transmission, genetic characteristics (presence or absence of CCR5 receptors) and can be higher or lower.

Most people's immune systems successfully control HIV without requiring treatment for many years.

CD4+ cell count is a blood test that determines how well the immune system is functioning in people with the human immunodeficiency virus (HIV). CD4+ cells are a type of white blood cell. White blood cells play an important role in the fight against infections. CD4+ cells are also called T lymphocytes, T cells, or T helper cells.

HIV attacks CD4+ cells. The CD4+ cell count helps determine whether other infections (opportunistic infections) may occur. The CD4+ cell count trend is more important than the value of a single test because the data can change from day to day. The trend in CD4+ cell count over time demonstrates the impact of the virus on the immune system. In untreated HIV-infected people, the CD4+ cell count usually declines as HIV progresses. A low CD4+ cell count often indicates a weakened immune system and a higher chance of developing opportunistic infections.

Why testing is done

The CD4+ cell count is measured to:

Observing how HIV infection attacks your immune system.

Help to make a timely diagnosis of acquired immunodeficiency syndrome (AIDS). HIV leads to AIDS, a long-term chronic disease for which there is no cure.

Determining when it is best to start antiretroviral therapy, which will reduce the rate of development of HIV infection in the body. For more detailed information, please refer to the “Results” section.

Determining your risk of developing other infections (opportunistic infections).

Determining when is the best time to start preventative treatment for opportunistic infections, such as taking medications to prevent Pneumocystis pneumonia (PCP).

The CD4+ cell count measured when you are diagnosed with HIV serves as the reference point against which all subsequent CD4+ cell counts will be compared. Your CD4+ cell count will be measured every 3 to 6 months, depending on your health, your previous CD4+ cell count, and whether you are taking highly active antiretroviral therapy (HAART).

How to prepare for the test

Before taking this test, consult a professional who can advise you on the meaning of the test results. Find out how this test relates to your HIV infection.

How the test is carried out

The healthcare professional performing the blood draw will do the following:

Place an elastic bandage around your arm above the elbow to stop blood flow. This enlarges the veins that are below the level of the bandage, making it easier for the needle to enter the vein.

Wipe the needle with alcohol.

Inserts a needle into a vein. It may take more than one try.

Attach a blood collection tube to the needle.

When the required amount of blood has collected, he will remove the bandage from your arm.

Apply a gauze compress or cotton swab to the site where the needle punctures the skin after removing it.

First, he will apply pressure to the puncture site, and then apply a bandage.

How will it feel

You may not feel anything during the injection, or you may feel slight pain as the needle passes through the skin. Some people experience a burning pain while the needle is in the vein. However, most people experience no or minimal discomfort when the needle is inserted into a vein. How much pain you experience will depend on the skill of the healthcare professional who takes the blood sample, as well as the condition of your veins and your sensitivity to pain.

For HIV infection, a blood test for CD4 cells is prescribed. Based on the indicators of this test, one can judge the state of the human immune system. The test results also indicate the stage of the disease and the degree of damage to the body by the virus. What are the standards for this analysis? Does a low level of such cells always indicate acquired immunodeficiency syndrome? We will consider these questions in the article.

What it is

The most important cells of the human immune system are lymphocytes. They are divided into 3 groups:

B-lymphocytes. They are able to remember and recognize pathogens that have previously entered the body. When dangerous microorganisms re-enter this type of lymphocyte, they produce antibodies - immunoglobulins. Thanks to these cells, a person develops immunity against certain infectious pathologies.
NK lymphocytes. They destroy the body's own cells that have become infected and undergo malignant degeneration.
T-lymphocytes. This is the most numerous group of protective cells. They detect and destroy pathogens.

CD4 cells are a type of T lymphocyte. Next we will look at their functions in more detail.

Cell functions

In turn, T-lymphocytes are divided into several types, which perform different functions in the body:

T-killers. Kill pathogens.
T-helpers. These are helper cells. They enhance the immune system's response to invading infectious agents.
T-suppressors. This type of lymphocyte regulates the strength of the immune system's response to invading microbes.

On the surface of T helper cells there are molecules of the CD4 glycoprotein. They work as receptors that recognize antigens from pathogens. Helper T cells are otherwise called CD4 or CD4 T cells. They transmit information about the invasion of infectious agents to B lymphocytes. Next, the process of producing antibodies against foreign antigens begins.

This is how CD4 cells function in a healthy person. They serve to protect the body from pathogens. However, with HIV infection, serious disruptions in the functioning of T-helper cells occur. We'll look at them next.

Acquired immunodeficiency

In HIV, CD4 cells are primarily affected. It is T helper cells that become the main target for the virus.

Penetrates CD4 and replaces the normal genetic code of these cells with a pathological one. As T-helper cells multiply, more and more copies of the virus are created. This is how the infection spreads in the body.

In the initial stages of the disease, there is an increased production of T-helper cells. This is the body's response to the invasion of the virus. It is no coincidence that people with HIV-positive status note that in the early stages of infection they rarely suffered from colds.

However, prolonged residence of the virus in the body and its spread depletes the immune system. Subsequently, HIV-infected people experience a sharp drop in CD4 cell levels. This indicates that the person has been infected with the immunodeficiency virus for quite some time. With a low level of these cells, the patient has virtually no resistance to dangerous microbes. The patient becomes extremely susceptible to any infectious diseases that occur in a severe form.

What test do you need to take?

To find out the state of your immune system, you need to take a CD4 T-cell test. Venous blood is taken for a sample. The test is carried out in the morning on an empty stomach. Before the study, you need to exclude physical and psycho-emotional stress, drinking alcohol and smoking.

Indications for the test

A blood test for CD4 T cells is prescribed for HIV-positive patients. This test is carried out for the following purposes:

to monitor the dynamics of the development of HIV infection;
to determine the stage of pathology;
to determine the need for drug therapy.

As already mentioned, the presence and spread of the HIV virus in the body is always accompanied by a sharp decrease in the body’s resistance to pathogens. The analysis helps to assess the likelihood of a patient developing infectious pathologies and promptly carry out antiviral and preventive treatment.

Normal results

Let's look at acceptable CD4 cell counts. The standards depend on the age of the person, as well as on the unit of measurement. Most often, these cells are calculated as a percentage of the total number of lymphocytes. Some laboratories determine the concentration of T-helper cells in 1 liter of blood.

What percentage of all types of lymphocytes are CD4 cells in a healthy person? Indicators from 30 to 60% are considered the norm. These are reference values for adult patients.

If the laboratory evaluates the concentration of T-helpers in 1 liter of blood, then for adults, values from 540 x 10 6 to 1460 x 10 6 cells/l are allowed.

Normally, CD4 cells are produced in higher quantities in a healthy child than in adults. Reference values for T-helper cells for children are given in the table below:

Reasons for the increase

Typically, the analysis evaluates not only the indicators of T-helper cells, but also the number of T-suppressor cells (CD8 cells). Their ratio has important diagnostic significance. Very often, an increase in the concentration of T-helpers is accompanied by a decrease in the activity of suppressors. This leads to an excessive and inappropriate immune response. In this case, lymphocytes can attack healthy tissues of the body. This is a sign of the following autoimmune pathologies:

systemic lupus erythematosus;
scleroderma;
rheumatoid arthritis;
autoimmune thyroiditis;
dermatomyositis.

Increased CD4 concentrations are also observed in patients with liver cirrhosis and hepatitis.

Reasons for the decline

The most common cause of a drop in CD4 count is HIV infection. This indicates the progression of the disease and a high risk of infection with bacterial, viral and fungal pathologies. When these cell counts are low, doctors prescribe a course of preventive therapy.

In this case, always pay attention to the number of T-suppressors. Their increase and decrease in the level of helper lymphocytes is observed in Kaposi's sarcoma. This serious complication often occurs in patients in the later stages of AIDS.

However, HIV is not the only reason for the decrease in the concentration of T-helper cells. The number of these cells also decreases in the following diseases and conditions:

chronic protracted infectious pathologies (for example, tuberculosis or leprosy);
congenital disorders of the immune system;
nutritional deficiency;
cancerous tumors;
radiation sickness;
after burns and injuries;
in old age;
under systematic stress.

Taking certain medications can also affect your CD4 counts. Drugs that reduce the level of T-helper cells include corticosteroid hormones, cytostatics, and immunosuppressants. Therefore, before taking the test, it is recommended to avoid taking such medications.

What to do if a person with HIV-positive status has a test showing a sharp decrease in CD4? Such test results indicate the spread of the virus and serious damage to the immune system. The patient needs to take preventive medications.

In this case, the results of the T-helper test are taken into account along with the data from the viral load analysis. This test shows the number of copies of the HIV pathogen per unit of blood.

CD4 counts less than 350 x 10 6 cells/l (no more than 14% of total lymphocytes) are considered dangerous. These results indicate that HIV infection may progress to the stage of active manifestations of AIDS. If the patient has a high viral load, then special treatment is necessary. It's called antiretroviral therapy. Patients are prescribed three or four types of drugs that suppress the reproduction of the pathogen at different stages of its development. This treatment allows people living with HIV to remain in remission.

There is also the concept of opportunistic infections. These are diseases that rarely occur in people with normal immune systems. However, such pathologies are quite common with HIV. The test shows the likelihood of occurrence of such diseases:

When cell counts are less than 200 x 10 6, the patient has an increased risk of developing pneumonia of fungal etiology (pneumocystosis).
If CD4 falls below the level of 100 x 10 6, then this is fraught with the occurrence of toxoplasmosis and meningitis caused by fungi (cryptococcosis).
If T-helper levels drop below 75 x 10 6, then the patient’s risk of mycobacteriosis increases. This is a severe form of tuberculosis that occurs only in AIDS.

With such analysis data, the patient needs prevention of opportunistic infections. The patient is prescribed a preventive course of antifungal and antibacterial drugs.

CD4 cells are T lymphocytes that have CD4 receptors on their surface (see.
general information). This subpopulation of lymphocytes is also called T helper cells. Along with
with viral load, the CD4 cell level is the most important supporting marker,
used in HIV medicine. It serves as the most reliable risk assessment criterion
development of AIDS. The obtained indicators can be roughly classified into two
groups: above 400-500 cells/µl – corresponds to a low incidence of severe
manifestations of AIDS, below 200 cells/μl – accompanied by a significant increase
the risk of developing manifestations of AIDS with increasing duration of immunosuppression.
However, most often AIDS-related diseases develop at CD4 levels
less than 100 cells/µl.
When determining the CD4 cell level (most often by flowcytometry), you should
take several factors into account. Relatively fresh material should be used for analysis.
blood collected no more than 18 hours ago. Depending on laboratory
conditions, the lower limit of the normal range is 400 to 500 cells/µl.
The basic rule regarding the assessment of viral load also applies to the analysis of the level
CD4 cells: always use the same laboratory
(with experience in performing similar analyses). The higher the value, the higher it is
fluctuations, so deviations of 50-100 CD4 cells/μl are quite possible. In one of
studies with a real CD4 level of 500 cells/μl 95% confidence
the range was from 297 to 841 cells/μl. At 200 cells/µl 95%
the confidence interval was 118 to 337 cells/µl (Hoover 1993).
If an unexpected CD4 count is obtained, the test must be repeated. Should
remember that in the presence of an undetectable viral load, even a pronounced decrease
CD4 cell levels should not be of concern. In such cases, you can navigate
on the relative number of CD4 cells (percentage), as well as on the ratio
CD4/CD8, since relative measures are usually more reliable and less susceptible to
fluctuations. As approximate reference indicators, you can use
the following values: if the CD4 count is more than 500 cells/µl, it is expected that
the relative value will be more than 29%, with a CD4 cell level of less than 200 cells/μl
it will be below 14%. In addition, the reference values of relative indicators and
ratios vary depending on the laboratory. If significant
discrepancies between absolute and relative CD4 cell counts must be
be careful in making therapeutic decisions - it is better to do it again
control analysis! Other blood test indicators should also be taken into account, including
including the presence of leukopenia or leukocytosis.
Today, doctors often forget that CD4 cell test results are
vital. The road to the doctor and conversation about the examination results for many
patients is a huge stress (“it’s worse than before the exam”), and the choice
Incorrect reporting of presumptively negative results may
lead to reactive depression. Therefore, it is extremely important to inform the patient about
physiological and methodologically determined fluctuations in analysis results.
A decrease from 1200 cells/µl to 900 cells/µl most often does not matter! And many
patients, on the contrary, will perceive a message about such results as
catastrophe. Attempts should also be made to reduce euphoria in patients with unexpected
good performance. This will save the doctor from explanations and losses for a long time.
time, as well as from a feeling of guilt for the patient’s unjustified hopes. Fundamental
a problem should be considered the communication of test results by employees related to
nursing staff (they do not have fundamental knowledge about
HIV infection).
Upon initial achievement of normal CD4 levels and sufficient suppression
Virus replication can be analyzed every six months. Probability of recurrence
A CD4 count of less than 350 cells/µl is low (Phillips 2003). Falling lower
a clinically significant limit of 200 cells/μl is generally observed extremely rarely. According to
results of one of the new studies, the likelihood of this phenomenon in patients,
once achieving a CD4 count of 300 cells/μl and viral load suppression below
200 copies/ml, over 4 years is less than 1% (Gale 2013). In this regard, measurement
CD4 count in stable patients is no longer recommended in the US
(Whitlock 2013). Patients who still wish to undergo more frequent monitoring
immune status, in most cases you can reassure yourself with the phrase that with the level
CD4 cells nothing bad can happen as long as suppression is maintained
virus replication.

Figure 2: Decrease in absolute and relative (dashed line) CD4 cell counts in
patients who did not receive treatment. On the left is a patient suffering from HIV infection for almost 10 years,
Pay attention to the pronounced fluctuations in the indicator. On the right is a patient who, within 6
months there was a sharp decline in CD4 levels from more than 300 cells/μl to 50 cells/μl. U
the patient developed AIDS (cerebral toxoplasmosis), which probably could have been
prevented by timely initiation of ART. This case is a clear argument in
the benefit of regular monitoring even with supposedly good indicators.

Factors influencing the indicator
Along with methodologically determined fluctuations, there are a number of other
factors influencing this laboratory indicator. These include
intercurrent infections, leukopenia of various origins, immunosuppressive therapy.
Against the background of opportunistic infections, as well as syphilis, the number of cells
CD4 is reduced (Kofoed 2006, Palacios 2007). Also to a temporary decrease in this
indicators are carried out by significant physical activity (marathon running), surgical
interventions or pregnancy. Even the time of day can play a role: CD4 levels during the day
low, then increases and reaches a maximum in the evening, around 20.00 (Malone 1990).
The role of mental stress, which is often cited by patients, on the contrary, is
insignificant.

Most patients not receiving therapy experience relatively continuous
decreased CD4 cell levels. However, there is a variant of stick-slip flow
a disease in which, after a period of relative stability, there is rapid
Decrease in CD4 count – Figure 2 shows one such case. According to
based on analysis of the COHERE database, which includes 34,384 naive
HIV-infected patient, the average annual decrease in CD4 count was
78 cells/µl (95% confidence interval – 76-80 cells/µl). Reduction amplitude
had a close relationship with the magnitude of the viral load. When the viral load increases by
1 Log there was a decrease in CD4 count of 38 cells/µl/year (COHERE 2014). Connections with
patient's gender, ethnic origin, or active drug use
has not been identified, despite its supposed existence.
The rise in CD4 cell levels during ART is often biphasic (Renaud 1999, Le
Moing 2002): after a rapid rise in the first 3-4 months, the rate of increase in cell levels
CD4 decreases. In one study of almost 1,000 patients,
in the first 3 months, the monthly rise in CD4 count was 21 cells/μl. During
subsequent 21 months, the monthly rise in CD4 levels was only 5.5 cells/μl
(Le Moing 2002). The rapid increase in CD4 cells at the initial stage is probably due to their
redistribution in the body. Then the active production process is added
naïve T cells (Pakker 1998). Perhaps at the initial stages it also plays a role
decrease in the intensity of apoptosis (Roger 2002).
There continues to be debate as to whether restoration of the immune system is
background of long-term suppression of viral replication, continuous, or it continues
only 3-4 years, reaching a plateau phase with no further rise (Smith 2004, Viard
2004). The degree to which the immune system recovers is influenced by a number of different factors.
The degree of suppression of viral replication plays an important role: the lower the viral load,
the better the effect (Le Moing 2002). And the higher the CD4 level at the time of starting ART, the
higher is their absolute increase in the future (Kaufmann 2000). Moreover, in the long term
naïve T cells also take part in the restoration of the immune system,
available at the initial stage (Notermans 1999).

Figure 3: Rise in absolute (solid line) and relative (dashed line) quantity
CD4 cells in two previously treated patients. Arrows indicate the time of ART initiation.
In both cases, fairly pronounced oscillations are observed, the amplitude of which is sometimes
reaches 200 CD4 cells or more. Patients should be advised that certain values
indicators do not convey much information.

Figure 4: Viral load dynamics (dashed line, right axis, logarithmic
presentation of data) and absolute (dark line) CD4 cell count against the background of long-term
ART. Left: Significant problems with treatment adherence were observed at the initial stage,
Only after the development of AIDS in 1999 (TBC, NHL) did the patient begin to regularly take ARP, which
accompanied by rapid and adequate restoration of immunity, in the last 10 years
the plateau level remains. It is necessary to raise the question to what extent the measurement should be continued
CD4 level. On the right is an elderly patient (60 years old), who took 2 breaks in treatment and has
moderate restoration of immunity.

In addition, the age of the patient is of great importance (Grabar 2004). The larger the sizes
thymus and the more active thymopoiesis, the more significant the increase in the level of CD4 cells will be (Kolte
2002). Due to the fact that degeneration of the thymus is often observed with age, the process
CD4 cell count increases in older people are different from those in younger patients
(Viard 2001). However, we have seen patients with poor recovery dynamics
CD4 level already at 20 years of age and, conversely, 60-year-old patients with extremely good dynamics
recovery. The ability of the immune system to regenerate is characterized sharply
pronounced individual differences, and until now there are no methods
allowing one to predict this ability with sufficient reliability.
There are likely to be specific antiretroviral therapy regimens, e.g.
DDI+tenofovir, which will reduce immune recovery
pronounced compared to others. In some modern studies
It has been established that particularly good recovery is observed when taking
CCR5 antagonists. It is also necessary to pay attention to the accompanying
immunosuppressive therapy, which may affect the recovery process
immunity.

Practical guidelines for monitoring CD4 cell counts
 The basic principle is the same as for measuring viral load: tests should be
performed in the same laboratory (with the necessary experience).
 The higher the indicators, the more pronounced the fluctuations (many factors should be taken into account
additional factors) – you always need to look at relative indicators and
CD4/CD8 ratio compared to baseline data!
 Don't go crazy (and don't let patients go crazy) about the expected decline
CD4 level: with sufficient suppression of the viral load, a decrease in this
indicator may not be due to the progression of HIV infection! Take care
nerves! If the results are extremely unexpected, the analysis should be repeated.
 When the viral load decreases to an undetectable level, analysis at the cell level
It is enough to perform CD4 once every three months.
 With a pronounced suppression of viral replication and a normal CD4 level,
Apparently, it is also possible to reduce the frequency of monitoring this indicator (but to viral
this does not apply to the load!). Its value as an auxiliary marker of flow
infection when the patient is stable is controversial
 In patients not receiving therapy, CD4 cell count remains critical
auxiliary marker!
 CD4 count and viral load should be discussed with your doctor. The patient is not
must be left alone with the results of the examination.

Information on further typical dynamics of CD4 cell levels is presented in the section
Principles of treatment. So there are studies on detailed study of cell function
CD4 as part of the qualitative ability of the immune system to fight against specific
antigens (Telenti 2002). However, these methods are not required for use in
standard diagnostics, their usefulness is still considered questionable. When-
They may perhaps help identify those few patients who have
danger of developing opportunistic infections even with normal cell levels
CD4. Next, two more examples from practice will be presented, reflecting the dynamics
immune status and viral load during long-term therapy.

Cellular and humoral immunity

Your body copes with various infections in two main ways:

1) The reaction of humoral immunity is based on antibodies.

HIV is usually diagnosed through an antibody test, which looks at the body's response to HIV. Usually the reaction begins within two to three weeks, but sometimes it occurs over several months or more.

2) Cellular immunity is based on the reaction of CD4 and CD8 cells

T cells are a type of white blood cell (lymphocyte). The main types of T cells are CD4 and CD8 cells.

CD4 cells are sometimes called helper cells because they mobilize the immune system by sending signals to CD8 cells.

CD8 cells, in turn, are called killer cells because they recognize and kill cells infected with the virus.

Sometimes these processes and functions overlap.

In general, your body uses cellular immunity to fight viruses and to fight HIV.

Macrophages are another type of slightly larger white blood cell that engulf or suppress infections or dead cell waste.

They also send signals to other immune system cells.

^ Model of CD4 count after HIV infection without therapy

The CD4 count (full name: CD4+ T-cell count, but also called CD4+ T-cell count or T4) is a blood test result that shows how many of these cells are contained in a cubic millimeter of blood.

The CD4 count is a very good “surrogate marker” for determining how much HIV has attacked the immune system. It indicates the risk of other infections and when treatment should be started.

The average CD4 count for an HIV-negative person is between 600 and 1600, but some people may have higher or lower levels.

Within a few weeks of HIV infection, your CD4 count usually drops.

Then, as the immune system begins to fight back, it rises again, although not to the level it was before HIV infection.

This level is usually called the CD4 set point, which usually stabilizes within 3-6 months after infection, but this process can take much longer.

Subsequently, the number of CD4 gradually decreases over the years. The average drop in CD4 count is about 50 cells/mm 3 annually. Depending on the person, this speed may be higher or lower.

Most people's immune systems successfully control HIV without requiring medication for many years.

The time it takes for the CD4 count to drop (eg to 200 cells/mm3) varies from person to person.

Approximate time to reduce CD4 count to 200 cells/mm 3 in HIV+ people:

10% - for 3-4 years

70% - over 5-9 years

10% - for 10-12 years

In those who were seriously ill at the time of infection (during the period of seroconversion), the decline in CD4 counts often occurs more quickly.

^ Interpretation of CD4 results: CD4 count and CD4 percentage

CD4 count alone doesn't tell you much. It takes multiple results over time to see a trend.

When there are several results, you will be able to see whether there is a decrease or increase, what the rate of change or stabilization is.

Your CD4 count can fall or rise depending on the time of day, the fat content of the food you ate, whether you just walked quickly up the stairs, whether you have other infections, or whether there were simply more or fewer cells in a given blood sample.

Therefore, the trend shows an average level of results.

“Absolute” reading of the amount of CD4. This is the number of CD4 cells per cubic millimeter (cells/mm3) or microliter (cells/uL) of blood.

^ If your test result is unexpectedly high or low, then, if possible, it should be confirmed by performing a second test.

CD4 percentage (CD4%) is a more consistent indicator of whether changes have occurred in the immune system. This is the percentage of CD4 cells among all lymphocytes.

A CD4 percentage of about 12-15% corresponds to a CD4 count below 200 cells/mm 3 .

A CD4 percentage of about 29% corresponds to a count above 500 cells/mm3, but for higher values the range is wider.

For an HIV-negative person, this percentage is on average about 40.

The absolute amount of CD4 is not calculated for children; for them the percentage of CD4 is used.

Children usually have much higher CD4 counts than adults.

Infants have higher CD4 counts than children.

Over time, as you grow older, the amount of CD4 gradually decreases.

Because there is huge variation in CD4 counts among children, children with HIV are monitored by percentage of CD4 rather than by count.

^ Re-infection with HIV

When an HIV-infected person is exposed to the virus again, they may become infected with a different strain of HIV.

It is unknown how often reinfection may occur, and the risk factors for reinfection are unknown.

Recent studies have not shown a high risk, but it is a danger that needs to be kept in mind.

Many of these cases involve people in the early stages of infection.

There are also cases where a person receiving treatment becomes infected with a virus that is resistant to drugs, and then the treatment stops working.

Therefore, re-infection is dangerous.

^ There is no risk of reinfection for two people with the same non-resistant virus or the same resistant virus.

What is a viral load test?

A viral load test determines the amount of HIV in a blood sample.

After infection, the viral load is very high, but the body fights the infection and significantly reduces the level of virus in the blood. After some time, usually several years, the level of the virus rises again. It is usually very high (about 50,000 - 200,000 copies/ml) by the time the CD4 cell count drops to 200 cells/mm3.

A viral load test is used after starting treatment to check whether the medications are working.

If ARV therapy reduces the viral load to 50 copies/ml, then treatment can continue for many years.

Viral load tests showed that HIV was never a dormant virus. It is a gradually progressive infection that is always active.

These tests measure the amount of virus in small blood samples, making calculations easier. But this means that the individual results of any one test are not sufficiently accurate and may have a threefold error.

So if the viral load test result is 30,000, the actual result could potentially be between 10,000 and 90,000 copies/mL.

When using CD4 tests, it is important to evaluate the trend of multiple test results to monitor for any changes.

Never make any treatment decisions based on the results of one test.

What happens to your viral load after infection?

Infection This is the time when the virus infects the first cells. It takes several hours for these infected cells to travel to the lymph nodes.

Over the next few days or weeks, the virus continues to multiply. At this time, the level of viral load increases very quickly.

Seroconversion– as the viral load increases, high levels of viral activity cause symptoms in 50-80% of people, which include sweating, fever, temperature, weakness, fatigue, etc.

The body mounts an immune response to this new infection and begins producing antibodies to fight the virus. After infection, it may take 1 to 3 months for an immune response (antibody to HIV) to be strong enough to be detected by an HIV test.

^ Primary HIV infection – also called early or acute infection. The term "primary infection" is usually used to describe the first six months after infection.

^ Chronic infection is the term for HIV infection after the first six months. Chronic infection can last for many years. It takes two to ten years before most people need treatment. With treatment, chronic infection can last 20, 30, 40 or more years.

^ Late stage of infection - AIDS is the term used to describe the most serious stage. It occurs in people who do not have access to medications, are diagnosed late, or for whom treatment fails.

^ Impact of co-infections on viral load

Other infections can affect your HIV viral load.

Sexually transmitted infections, such as herpes, gonorrhea, and syphilis, increase the level of HIV in sexual fluids (sperm and vaginal fluids).

Viral infections such as influenza can increase viral load levels when the infection is active.

Reactions to some vaccines can also temporarily increase your viral load.

^ Reservoirs in the body where drugs cannot affect the virus

Although we measure viral load in the blood as a distinct environment of the body, several other important areas of the body that have barriers limit the freedom of movement of HIV and HIV drugs.

These include the genitals, CSF - the cerebrospinal fluid - the fluid that circulates in the brain and spine, and the brain itself.

HIV may develop differently in these environments. Some drugs penetrate these environments better than others.

Resistance may differ in different environments - it usually develops in one environment and can spread to other parts of the body. Viral load levels may vary in each environment.

This makes HIV a very complex disease. In practice, because most tests use blood, it is impossible to know exactly what is happening in other areas of the body.

^ Importance of viral load with and without treatment

Without treatment:

When a person is not taking ARVs, CD4 counts are more important than viral load.

Viral load tests are also useful, but they are not as important in preventing the risk of infections or in determining when to start treatment.

An exception can be made when your viral load is very high. If your viral load is more than 100,000 to 500,000 copies, this may be a reason to start treatment if your CD4 count is above 200.

During treatment:

If you are taking treatment for HIV, viral load tests may be more important than CD4 level tests. If a patient is on therapy, it is likely that their CD4 counts are already rising.

In treatment, the viral load is a good indicator of how long treatment with the prescribed regimen may last. Sometimes viral load tests are used to check adherence.

If your viral load drops to 50 copies/ml, treatment with the prescribed regimen can last for many years. If the viral load is low, resistance can only develop if you are late or miss taking your medications.

If it has decreased, but, for example, only to 500 copies/ml, then enough HIV is produced every day to develop resistance to your combination of drugs.

If a viral load test is not available, your doctor will rely on CD4 tests or clinical symptoms.

Without treatment, the viral load in children is higher than in adults, but when using therapy in children, it is just as important to reduce the viral load to 50 copies/ml or below.

It is not known how often viral load testing should be done. UK and US guidelines recommend viral load testing every 3–6 months when the patient is not on therapy and every 3 months while the patient is on therapy. It is also recommended to take a viral load test one month after starting treatment or after making any changes to the treatment regimen.

^ Viral life cycle, drug resistance and adherence

All HIV-positive people who are not on treatment produce several billion copies of HIV in their bodies per day. By making so many copies of itself, the virus often makes mistakes. They are called mutations.

When you are not taking treatment, there is no reason for any particular mutation to occur because they are usually not as strong as the original virus.

However, when you are on treatment, some mutations that appear will be immune to the drugs you are taking. These resistant mutations will continue to multiply and eventually become the main type of virus in your body. Then you develop resistance to the medications you are taking and to some similar medications. This is called cross-resistance.

The higher your viral load while you are on treatment, the more likely you are to develop resistance. Therefore, it is very important to reduce the viral load as much as possible (ideally to 20 copies/ml) and to do this as quickly as possible.

Resistance and commitment are closely related. If you miss or are late taking one or all of your medications, your chances of developing resistance increase. This occurs because during this period the level of drugs in the blood is much lower than the minimum safe level.

^ What is the relationship between CD4 and viral load?

Although they measure completely different things, viral load test results and CD4 counts are usually related:

Typically, when your viral load is low, your CD4 cell count will be high.

Likewise, if the CD4 count is low, the viral load will be high.

A few weeks after infection, when HIV levels are very high, the CD4 count drops.

As the immune system reduces the viral load, the CD4 count may rise again.

Sometimes there is a lag period between changes in viral load and CD4 count:

1) after starting treatment, the viral load drops very quickly, but sometimes several months pass before CD4 counts begin to increase.

2) if treatment does not help and the viral load begins to rise again, CD4 counts may continue to rise for some time, despite the fact that CD4 cell counts usually fall as viral load levels increase.