Topic: Immune status and viral load. Model of CD4 count after HIV infection without therapy Stages of HIV infection by CD cells

CD4 (T-CELL) TESTS

WHAT ARE CD4 CELLS?
. WHY ARE CD4 CELLS IMPORTANT IN HIV?
. WHAT FACTORS AFFECT THE QUANTITY OF CD4?
. HOW ARE ANALYSIS RESULTS DISPLAYED?
. WHAT DO THE NUMBERS MEAN?

WHAT ARE CD4 CELLS?

CD4 cells are a type of lymphocyte (white blood cell). They are an important part of the immune system. Sometimes CD4 cells are called T cells. T-4 cells, or CD4+ cells, are called “helper” cells. They are the first to attack infections. T-8 cells (CD8+) are suppressive cells that complete the immune system response. CD8+ cells are also sometimes called “killer” cells because they kill cancer cells and cells infected by a virus.
Scientists are able to distinguish these cells thanks to specific proteins on the cell surface. A T-4 cell is a cell with CD4 molecules on its surface. This type of T cells is also called “CD4 positive” or CD4+.

WHY ARE CD4 CELLS IMPORTANT IN HIV?

When a person is infected with HIV, CD4 cells are first infected.

The genetic code of the virus becomes part of the cell. When CD4 cells divide, they make new copies of the virus.

If a person is infected with HIV for a significant period of time, the number of CD4 cells decreases. This is a sign that the immune system is gradually weakening. The lower the CD4 count, the more likely a person is to get sick.
There are millions of different families of CD4 cells. Each family is designed to combat a specific type of microorganism. As HIV reduces the number of CD4s, some families may be eliminated completely. Therefore, a person may lose the ability to fight certain types of microorganisms that these families were intended to fight. If this happens, you may develop opportunistic infections (See Booklet 500).

WHAT IS A CD4 TEST?

A small amount of blood is drawn from the finger and the presence of certain types of cells is measured. CD4 cannot be counted directly and is therefore calculated based on all white blood cells. CD4 cell count is imprecise.

WHAT FACTORS AFFECT THE QUANTITY OF CD4?

The number of CD4 cells fluctuates constantly. Time of day, fatigue, stress can affect test results. It is best to draw blood for analysis at the same time of day, all the time in the same laboratory.
Infections can greatly influence the amount of CD4. When the body fights an infection, the number of white blood cells (lymphocytes) increases, and the number of CD4 and CD8 cells also increases. Vaccination can have the same effect. Try not to take a CD4 test for several weeks after an illness or vaccination.

HOW ARE ANALYSIS RESULTS DISPLAYED?
Typically, CD4 test results are displayed as the number of cells per cubic millimeter of blood, or mm3. There is some disagreement about the normal range for CD4 counts, but typically it is between 500 and 1600; for CD8 cells the range is between 375 and 1100. In people with HIV, CD4 counts drop dramatically, in some cases dropping to zero.
The ratio of CD4 cells to CD8 cells is often indicated. This ratio is determined by dividing the CD4 value by the CD8 value. For healthy people, this ratio ranges from 0.9 to 1.9, which means that for every CD8 cell there are 1 to 2 CD4 cells. In people with HIV, this ratio is much lower, meaning there are significantly more CD8 cells than CD4 cells.
Because the CD4 count can fluctuate significantly, some doctors prefer to track the percentage of CD4 to the total lymphocyte count. If the test results show that % CD4 is 34%, this means that 34% of your lymphocytes are CD4 cells. This percentage is more stable than the amount of CD4. The normal range is 20% to 40%. A CD4 percentage below 14% means significant damage to the immune system and is a sign of AIDS in people with HIV.

WHAT DO THE NUMBERS MEAN?
The significance of the number of CD8 cells is unclear, but research in this area is ongoing.
The CD4 count is key to measuring the health of the immune system. The lower the number, the more damage HIV has caused. According to experts from the US Center for Disease Control, people with a CD4 cell count of less than 200 or 14% of cells are at the AIDS stage.

The CD4 count, along with viral load, is used to estimate how long a person will remain healthy. See Booklet 125 for more information on viral load testing.
The CD4 count is also used as an indicator of the need to initiate drug therapy.
When to start antiretroviral therapy (ART)?
If your CD4 count falls below 350, most doctors will recommend starting ART (see Booklet 403). Additionally, some doctors believe that a CD4 count below 15% is a sign to start aggressive ART, even if the CD4 count is quite high. More conservative doctors may suggest waiting until the CD4 count drops below 200 to begin therapy. One recent study showed that starting therapy when CD4 is below 5% produces poor results in most cases.
When to start taking medications to prevent opportunistic infections:
Most doctors prescribe medications to prevent opportunistic infections at these CD4 levels.

HIV is a virus that attacks the immune system. Our immune system contains a large number of cells that perform different functions:

• Leukocytes;
• Phagocytes;
• Macrophages;
• Neutrophils;
• T helper cells (CD4 lymphocytes);
• Killer T cells.

Each of these cells is responsible for a certain stage of the response to a foreign object. HIV affects only one group of cells – CD4 lymphocytes (T lymphocytes). They are responsible for recognizing foreign genes.

Based on the number of certain cells, the doctor draws conclusions about the patient’s condition. The AIDS test is based on the number of T lymphocytes (CD4 lymphocytes) in a blood sample.

Diseases for which a doctor may prescribe an AIDS test

If a blood test shows vague connective tissue diseases or an inflammatory process, an HIV test may be prescribed. A good marker of HIV is a sharp decrease in CD4 lymphocytes. In cases where other infections and a predisposition to a certain group of diseases (colds, for example) are identified, an HIV test is not performed.

Important! If an inflammatory process that has no basis is detected, it is necessary to take an HIV test.

Don't be alarmed if your doctor starts talking about testing for HIV. The diagnosis may not be confirmed. If the result is positive, it is important to start treatment as quickly as possible.

Norms

• Overwork of the body;
• Menstrual cycle;
• Epidemiological environment;
• Some medications.

The number of T-lymphocytes (helpers) is restored after rest.

If the absolute CD4 count does not recover within a certain period, your doctor may order an HIV test.

Decoding the result of an AIDS test

In a healthy person, all indicators should be normal. If one of the parameters changes, a viral load test is prescribed. Afterwards, the results of the blood test are compared with this indicator. This will help you determine the cause of the violation.

The lymphocyte count decreases in the case of an infectious disease, but is restored to normal levels after treatment. There will be no improvement in system performance in HIV patients. This is what the test is based on.

What is immune status

When determining a person’s immune status, blood parameters are examined:

• Total and relative number of lymphocytes;
• Number of helper t-lymphocytes;
• Phagocytic activity of macrophages;
• Changes in immunoglobulins of different classes.

Of all the above, only T-lymphocytes are specific to HIV.

Important! A decrease in CD4 lymphocytes indicates a terrible disease. An increase in their level indicates another inflammatory process.

What does the CD4 count tell you?

CD4 cells are found in the blood in a certain amount. If they decrease, the body quickly restores its numbers. When the immune system is suppressed, the number of lymphocytes decreases; the activity of T-suppressors, on the contrary, leads to the activation of defenses.

Viral cells multiply very quickly, so when infected with HIV, the level of T cells cannot return to normal levels.

Changes in CD4 count

CD4 cells are the first to respond to the penetration of a foreign agent into the body. A decrease in level indicates high activity of the virus.

The number of cells/µl may vary depending on:

• Time of day (it is higher in the morning);
• The presence of infectious diseases;
• Blood processing process (if the procedure is incorrect, cells may be destroyed);
• Medicines taken (hormonal and steroid drugs significantly affect this indicator).

CD4 percentage

When performing an HIV test, blood counts are often expressed as a percentage.

Helper cells CD3, D8, CD19, CD16+56, as well as the CD4–CD8 ratio decrease with a decrease in immune status. But these parameters do not indicate HIV.

Only the CD4 helper is specific to the immunodeficiency virus:

• If its content is 12-15%, then calculated in the blood there are 200 cells/mm 3 ;
• With values ​​from 29%, the cell content is from 450 cells/mm 3;

For an HIV-negative person, the value of this parameter is 40%.

When immune cells are damaged, immunity decreases. To determine the speed of this process, the viral load is calculated - the amount of foreign RNA per ml of blood. This parameter is prognostic in nature.

Women's immune systems are weaker, so the viral load, according to the study results, begins to decline much earlier than in men.

What does undetectable viral load mean?

The viral load may not be determined for several months. Depending on the activity of the virus, its number in the blood may vary. Then, if the sensitivity of the device is low, it will not detect the virus.

Important! An undetermined viral load does not mean that the virus has completely disappeared. Treatment for AIDS cannot be stopped, since without treatment, remission will occur and the amount of virus will increase.

Effect of vaccinations and infections

Vaccination or an infectious disease temporarily increases the viral load. Taking preventive medications, on the contrary, reduces it. To accurately determine the immune status after the listed procedures, you should wait some time. The period will be determined by the doctor depending on the circumstances.

What are the benefits of having an undetectable viral load?

HIV-positive people may have an undetectable viral load if:

• Correct antiretroviral therapy;
• Low level of virus progression.

This helps normalize the patient's condition. With numerous repeated courses, immunological tolerance may develop. The immunological response in this case stops responding to treatment. In this case, it is necessary to change the course of treatment. This can happen if:

• The course of treatment was not completed;
• The same course was repeated several times in a row;
• Individual insensitivity to prescribed medications.

Natural variations

The virus can be in the body in several stages:

• Incubation stage;
• Period of acute infection;
• Latent stage;
• Stage of secondary diseases;

During different periods of activity, viral load indicators change significantly. Within a few days, this parameter can change threefold, regardless of the course of treatment. Sharp short-term jumps may not affect the patient’s health. Determination of drug resistance is carried out several times. The final result is calculated as an average.

Taking suppressors leads to stabilization of the number of viruses in the blood.

Significant changes

If the number of HIV viruses remains high for several months, it is worth paying attention to this. Indicators that exceed the norm by 3 to 5 times are important. If the increase in CD4 counts goes away during treatment, you may need to change medications because your body has become desensitized to them.

Minimizing deviations

When taking an analysis for the amount of immunodeficiency virus and CD4 lymphocytes in the blood, it is worth understanding that different devices have different sensitivity. It may differ depending on the brand of the device or the calibration value. In order to minimize the error associated with devices, the analysis should be taken in the same clinic on the same device.

If one of the partners in a family is HIV-positive, there is a certain schedule in sexual life. If the viral load increases, you should completely abstain from sexual contact, as the likelihood of infection increases significantly.

When the virus threshold is reduced, using certain medications on the recommendation of a doctor, sexual activity can be resumed.

What is the threshold for determining current tests

Sensitive modern tests for diagnosing HIV are gradually increasing. Most devices in Russia are sensitive to virus numbers of 400-500 pieces/ml of blood. Some more expensive devices detect the virus using a standard method at a number of 50 pieces/ml.

Literature data indicates that some modern models are capable of recognizing HIV in numbers of only 2 pieces/ml of blood, but such technologies are not yet used in hospitals and private clinics.

Errors

Despite the high sensitivity of modern devices, errors still occur in determining viral load values. They are related to:

• Incorrect calibration of the device;
• Poor processing of flasks after previous analyses;
• Improperly prepared blood sample;
• The presence of drugs in the blood that reduce sensitivity.

These errors are corrected by retesting the same blood sample or a new portion.

The decision to start antiretroviral therapy

If tests show a high viral load over a long period of time, the doctor decides to prescribe a course of treatment. The start of treatment for HIV infection and taking medications does not begin immediately, but gradually. Most drugs are introduced into the course of treatment over a certain period so that the body gets used to a significant number of chemical aggressive components. The number of CD4 lymphocytes in the blood plays an important role in making this decision.

If a person cannot or does not want to start treatment, he must constantly get tested and monitor the level of lymphocytes in the blood.

Advice! If you have not started antiretroviral therapy, be regularly tested for HIV and your CD4 blood count. If you miss the critical minimum, the body may not cope. Recovery will take much more time, money and effort.

If your viral load increases while on therapy

If your viral load continues to increase after starting treatment, there are two options:

• Not enough treatment time has passed to restore normal values;
• The body is not sensitive to prescribed medications.

The decision on further actions is made by the doctor based on the tests and the patient’s condition.

How to improve your viral load test results

As a result of proper treatment, the amount of CD4 in the blood should gradually recover.

This will also be facilitated by:

• Proper nutrition;
• Rejection of bad habits;
• No stress;
• No overwork.

If you are not taking antiretroviral therapy

When deciding whether to start treatment or not, it is important to understand what antiretroviral therapy for HIV/AIDS is. These medications are aimed at suppressing the activity of the virus outside the body's cells. Due to this, during therapy the immune system of patients is restored.

The complex of drugs also includes those that help restore the body's natural defenses.

In the absence of such therapy, the virus is able to multiply unhindered, infecting more and more cells of the host’s immune system.

The first study is always a leukocyte count (see chapter “Hematological studies”). Both relative and absolute values ​​of the number of peripheral blood cells are assessed.

Determination of the main populations (T-cells, B-cells, natural killer cells) and subpopulations of T-lymphocytes (T-helpers, T-CTLs). For the initial study of immune status and identification of severe immune system disorders WHO recommended determination of CD3, CD4, CD8, CD19, CD16+56, CD4/CD8 ratio. The study allows us to determine the relative and absolute number of the main populations of lymphocytes: T cells - CD3, B cells - CD19, natural killer (NK) cells - CD3- CD16++56+, subpopulations of T lymphocytes (T helper cells CD3+ CD4+, T-cytotoxic CD3+ CD8+ and their ratio).

Research method

Immunophenotyping of lymphocytes is carried out using monoclonal antibodies to superficial differentiation tonsillitis on cells of the immune system, using flow laser cytofluorometry on flow cytometers.

The selection of the lymphocyte analysis zone is made based on the additional marker CD45, which is present on the surface of all leukocytes.

Conditions for taking and storing samples

Venous blood taken from the ulnar vein in the morning, strictly on an empty stomach, into a vacuum system to the mark indicated on the tube. K2EDTA is used as an anticoagulant. After collection, the sample tube is slowly inverted 8-10 times to mix the blood with the anticoagulant. Storage and transportation strictly at 18–23°C in an upright position for no more than 24 hours.

Failure to meet these conditions leads to incorrect results.

Interpretation of results

T lymphocytes (CD3+ cells). An increased amount indicates hyperactivity of the immune system, observed in acute and chronic lymphocytic leukemia. An increase in the relative indicator occurs with some viral and bacterial infections at the onset of the disease and exacerbations of chronic diseases.

A decrease in the absolute number of T-lymphocytes indicates a failure of cellular immunity, namely a failure of the cellular-effector component of immunity. It is detected in inflammation of various etiologies, malignant neoplasms, after injury, surgery, heart attack, smoking, and taking cytostatics. An increase in their number in the dynamics of the disease is a clinically favorable sign.

B lymphocytes (CD19+ cells) A decrease is observed with physiological and congenital hypogammaglobulinemia and agammaglobulinemia, with neoplasms of the immune system, treatment with immunosuppressants, acute viral and chronic bacterial infections, and the condition after removal of the spleen.

NK lymphocytes with the CD3-CD16++56+ phenotype Natural killer cells (NK cells) are a population of large granular lymphocytes. They are capable of lysing target cells infected with viruses and other intracellular antigens, tumor cells, as well as other cells of allogeneic and xenogeneic origin.

An increase in the number of NK cells is associated with activation of anti-transplant immunity, in some cases observed in bronchial asthma, occurs in viral diseases, increases in malignant neoplasms and leukemia, and in the period of convalescence.

Helper T-lymphocytes with the CD3+CD4+ phenotype An increase in absolute and relative amounts is observed in autoimmune diseases, possibly in allergic reactions, and in some infectious diseases. This increase indicates stimulation of the immune system to the antigen and serves as confirmation of hyperreactive syndromes.

A decrease in the absolute and relative number of T cells indicates a hyporeactive syndrome with a violation of the regulatory component of immunity and is a pathognomic sign for HIV infection; occurs in chronic diseases (bronchitis, pneumonia, etc.), solid tumors.

T-cytotoxic lymphocytes with the CD3+ CD8+ phenotype An increase is detected in almost all chronic infections, viral, bacterial, protozoal infections. Is characteristic of HIV infection. A decrease is observed in viral hepatitis, herpes, and autoimmune diseases.

CD4+/CD8+ ratio The study of the CD4+/CD8+ ratio (CD3, CD4, CD8, CD4/CD8) is recommended only for monitoring HIV infection and monitoring the effectiveness of ARV therapy. Allows you to determine the absolute and relative number of T-lymphocytes, subpopulations of T-helpers, CTLs and their ratio.

The range of values ​​is 1.2–2.6. A decrease is observed with congenital immunodeficiencies (DiGeorge, Nezelof, Wiskott-Aldrich syndrome), with viral and bacterial infections, chronic processes, exposure to radiation and toxic chemicals, multiple myeloma, stress, decreases with age, with endocrine diseases, solid tumors. It is a pathognomic sign for HIV infection (less than 0.7).

An increase in value of more than 3 – in autoimmune diseases, acute T-lymphoblastic leukemia, thymoma, chronic T-leukemia.

The change in ratio may be related to the number of helpers and CTLs in a given patient. For example, a decrease in the number of CD4+ T cells in acute pneumonia at the onset of the disease leads to a decrease in the index, but CTL may not change.

For additional research and identification of changes in the immune system in pathologies requiring assessment of the presence of an acute or chronic inflammatory process and the degree of its activity, it is recommended to include a count of the number of activated T-lymphocytes with the CD3+HLA-DR+ phenotype and TNK cells with the CD3+CD16++56+ phenotype.

T-activated lymphocytes with the CD3+HLA-DR+ phenotype A marker of late activation, an indicator of immune hyperreactivity. The expression of this marker can be used to judge the severity and strength of the immune response. Appears on T-lymphocytes after the 3rd day of acute illness. With a favorable course of the disease, it decreases to normal. Increased expression on T lymphocytes can occur in many diseases associated with chronic inflammation. Its increase was noted in patients with hepatitis C, pneumonia, HIV infection, solid tumors, and autoimmune diseases.

TNK lymphocytes with the CD3+CD16++CD56+ phenotype T-lymphocytes carrying CD16++ CD 56+ markers on their surface. These cells have properties of both T and NK cells. The study is recommended as an additional marker for acute and chronic diseases.

A decrease in them in the peripheral blood can be observed in various organ-specific diseases and systemic autoimmune processes. An increase was noted in inflammatory diseases of various etiologies and tumor processes.

Study of early and late markers of T-lymphocyte activation (CD3+CD25+, CD3-CD56+, CD95, CD8+CD38+) additionally prescribed to assess changes in IS in acute and chronic diseases, for diagnosis, prognosis, monitoring the course of the disease and therapy.

T-activated lymphocytes with the CD3+CD25+ phenotype, IL2 receptor CD25+ is a marker of early activation. The functional state of T-lymphocytes (CD3+) is indicated by the number of receptors expressing IL2 (CD25+). In hyperactive syndromes, the number of these cells increases (acute and chronic lymphocytic leukemia, thymoma, transplant rejection), in addition, their increase may indicate an early stage of the inflammatory process. In peripheral blood they can be detected in the first three days of illness. A decrease in the number of these cells can be observed with congenital immunodeficiencies, autoimmune processes, HIV infection, fungal and bacterial infections, ionizing radiation, aging, and heavy metal poisoning.

T-cytotoxic lymphocytes with the CD8+CD38+ phenotype The presence of CD38+ on CTL lymphocytes was noted in patients with various diseases. An informative indicator for HIV infection and burn disease. An increase in the number of CTLs with the CD8+CD38+ phenotype is observed in chronic inflammatory processes, cancer and some endocrine diseases. During therapy, the indicator decreases.

Subpopulation of natural killer cells with the CD3- CD56+ phenotype The CD56 molecule is an adhesion molecule widely present in nervous tissue. In addition to natural killer cells, it is expressed on many types of cells, including T-lymphocytes.

An increase in this indicator indicates an expansion of the activity of a specific clone of killer cells, which have less cytolytic activity than NK cells with the CD3- CD16+ phenotype. The number of this population increases in hematological tumors (NK-cell or T-cell lymphoma, plasma cell myeloma, aplastic large cell lymphoma), chronic diseases, and some viral infections.

A decrease is observed with primary immunodeficiencies, viral infections, systemic chronic diseases, stress, treatment with cytostatics and corticosteroids.

CD95+ receptor– one of the apoptosis receptors. Apoptosis is a complex biological process necessary to remove damaged, old and infected cells from the body. The CD95 receptor is expressed on all cells of the immune system. It plays an important role in controlling the functioning of the immune system, as it is one of the receptors for apoptosis. Its expression on cells determines the cells' readiness for apoptosis.

A decrease in the proportion of CD95+ lymphocytes in the blood of patients indicates a violation of the effectiveness of the last stage of culling defective and infected own cells, which can lead to relapse of the disease, chronicization of the pathological process, the development of autoimmune diseases and an increase in the likelihood of tumor transformation (for example, cervical cancer with papillomatous infection ). Determination of CD95 expression has prognostic significance in myelo- and lymphoproliferative diseases.

An increase in the intensity of apoptosis is observed in viral diseases, septic conditions, and drug use.

Activated lymphocytes CD3+CDHLA-DR+, CD8+CD38+, CD3+CD25+, CD95. The test reflects the functional state of T-lymphocytes and is recommended for monitoring the course of the disease and monitoring immunotherapy for inflammatory diseases of various etiologies.

This is a train that takes a person from the starting station - the moment of infection to the final station - the stage of AIDS. Immune status is the remaining distance to the final station. Viral load is the speed of a train. Therapy is a stop valve that stops the train and turns it back on. But if you pull the stop valve too late and at high speed, then the inertia of the train will no longer allow you to effectively brake it and engage reverse.

Immune status- This:

1. General condition of the immune system (e.g. “low SI”, “high SI”)
2. A special blood test to assess the state of the immune system (for example, “donate blood for I.S.”).

Immunodeficiency is a reduced immune status.

Why is immune status determined?

CD4 cell

An immune status test determines the number of different cells of the immune system. For people with HIV, the number of CD 4 cells (or T 4 lymphocytes) matters.

CD 4 or T 4 lymphocytes are white blood cells that are responsible for “recognizing” various pathogenic bacteria, viruses and fungi, which the immune system must destroy.

Information about the number of CD 4 cells allows the doctor to assess the level of health of the immune system, whether it is worsening or improving. The word "status" means state.

Respectively, the more of them, the better.

How is immune status measured?

Another CD4 cell

Immune status is measured using a special analyzer and is expressed as the absolute number of CD 4 cells in one microliter of blood (that is, not in the entire body). It is usually written as "cells/μl" or "μl -1".

In addition, the doctor can estimate the percentage that CD 4 makes up of the total number of white cells. This is the percentage (relative) number of CD 4 cells. Its normal value is 30-60%.

Why might immune status change over time?

HIV can infect CD 4 and make copies of itself in them, causing these cells to die. Although cells are killed by HIV every day, millions of CD 4s are produced to replace them. However, over a long period of time (years), the CD 4 count may decrease and even drop to dangerous levels. For most people with HIV, the CD 4 count usually declines over a period of years.

What does this or that number of CD 4 cells mean?

• from 500 to 1200 cells/μl is normal.
• from 350 to 500 cells/μl indicates a reduced functioning of the immune system (moderate immunodeficiency).
• from 200 to 350 cells/μl or begins to decline rapidly (severe immunodeficiency) is a reason to talk to your doctor about prescribing antiretroviral therapy.
• less than 200 cells/μl (profound immunodeficiency) - initiation of therapy is recommended, since with such an immune status there is a risk of AIDS-associated diseases.

What determines the number of CD4 cells?

The CD 4 cell count can rise and fall as a result of infections, stress, smoking, exercise, the menstrual cycle, birth control pills, time of day, and even the time of year.

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Exactly when does the AIDS stage begin?

In 2001, under the leadership of Academician of the Russian Academy of Medical Sciences V.I. Pokrovsky, a new edition of the domestic clinical classification of HIV infection was implemented.

Stage 1– “incubation stage” – the period from the moment of infection until the appearance of the body’s reaction in the form of clinical manifestations of acute infection and/or the production of antibodies. Its duration usually ranges from 3 weeks to 3 months, but in isolated cases it can last up to a year. During this period, HIV actively multiplies, but there are no clinical manifestations of the disease and antibodies to HIV have not yet been detected. Consequently, the diagnosis of HIV infection at this stage cannot be established using traditional laboratory methods. It can only be suspected on the basis of epidemiological data and confirmed during laboratory testing by the detection of human immunodeficiency virus, its antigens, and nucleic acids in the patient’s serum.

Stage 2– “stage of primary manifestations”, is associated with the manifestation of the body’s primary response to the introduction and replication of HIV in the form of clinical manifestations and/or the production of antibodies. The stage of primary manifestations of HIV infection can have several course options:

* 2A – “asymptomatic”, characterized by the absence of any clinical manifestations of HIV infection. The body's response to the introduction of HIV is manifested only by the production of antibodies.
* 2B – “acute infection without secondary diseases”, manifested by a variety of clinical symptoms. The most commonly recorded symptoms are fever, rashes on the skin and mucous membranes (urticarial, papular, petechial), enlarged lymph nodes, and pharyngitis. An enlarged liver, spleen, and diarrhea may occur. Sometimes aseptic meningitis develops, manifested by meningeal syndrome. In this case, lumbar puncture usually results in unchanged cerebrospinal fluid flowing out under increased pressure, and occasionally there is slight lymphocytosis in it. Similar clinical symptoms can be observed in many infectious diseases, especially in so-called childhood infections. Sometimes this variant of the course is called mononucleosis-like or rubella-like syndrome. In the blood of patients during this period, wide-plasma lymphocytes - mononuclear cells - can be detected, which further enhances the similarity of this variant of the course of HIV infection with infectious mononucleosis. Vivid mononucleosis-like or rubella-like symptoms are observed in 15-30% of patients. The rest have 1-2 of the above symptoms in any combination. Some patients may experience lesions of an autoimmune nature. With this course of the stage of primary manifestations, a transient decrease in the level of CD4 lymphocytes is often observed.
*

2B – “acute infection with secondary diseases”, characterized by a significant decrease in the level of CD4 lymphocytes. As a result, against the background of immunodeficiency, secondary diseases of various etiologies appear (candidiasis, herpetic infection, etc.). Their manifestations, as a rule, are mild, short-term, respond well to therapy, but can be severe (candidal esophagitis, Pneumocystis pneumonia) and in rare cases, even death is possible.

In general, the stage of primary manifestations, which occurs in the form of acute infection (2B and 2C), is recorded in 50-90% of patients with HIV infection. The onset of the stage of primary manifestations, which occurs in the form of an acute infection, is usually noted in the first 3 months after infection. It can precede seroconversion, that is, the appearance of antibodies to HIV. Therefore, at the first clinical symptoms, antibodies to HIV proteins and glycoproteins may not be detected in the patient’s serum.

The duration of clinical manifestations in the second stage can vary from several days to several months, but they are usually recorded within 2-3 weeks. Clinical symptoms of the stage of primary manifestations of HIV infection can recur.

In general, the duration of the stage of primary manifestations of HIV infection is one year from the onset of symptoms of acute infection or seroconversion. In prognostic terms, the asymptomatic course of the stage of primary manifestations of HIV infection is more favorable. The more severe and longer (more than 14 days) this stage occurs, the greater the likelihood of rapid progression of HIV infection.

The stage of primary manifestations of HIV infection in the vast majority of patients becomes subclinical, but in some patients it can immediately pass into the stage of secondary diseases.

Stage 3– “subclinical stage” is characterized by a slow increase in immunodeficiency, which is associated with compensation of the immune response due to modification and excessive reproduction of CD4 cells. The rate of HIV reproduction during this period, compared to the stage of primary manifestations, slows down.

The main clinical manifestation of the subclinical stage is persistent generalized lymphadenopathy (PGL). It is characterized by an enlargement of at least two lymph nodes, in at least two unrelated groups (not counting the inguinal ones), in adults to a size in diameter of more than 1 cm, in children - more than 0.5 cm, persisting for at least 3 years. -x months. Upon examination, usually the lymph nodes are elastic, painless, not fused with the surrounding tissue, and the skin over them is not changed.

Enlarged lymph nodes at this stage may not meet the criteria for PGL or may not be registered at all. On the other hand, such changes in the lymph nodes can be observed in later stages of HIV infection; in some cases, they occur throughout the entire disease, but in the subclinical stage, enlarged lymph nodes are the only clinical manifestation.

The duration of the subclinical stage ranges from 2-3 to 20 or more years, but on average it lasts 6-7 years. The rate of decrease in the level of CD4 lymphocytes during this period averages 0.05-0.07x109/l per year.

Stage 4– “stage of secondary diseases”, is associated with depletion of the CD4 cell population due to ongoing HIV replication. As a result, against the background of significant immunodeficiency, infectious and/or oncological secondary diseases develop. Their presence determines the clinical picture of the stage of secondary diseases.

Depending on the severity of secondary diseases, stages 4A, 4B, 4C are distinguished.

* 4A usually develops 6-10 years after infection. It is characterized by bacterial, fungal and viral lesions of the mucous membranes and skin, and inflammatory diseases of the upper respiratory tract. Typically, stage 4A develops in patients with a CD4 lymphocyte count of 0.5-0.35x109/L (in healthy individuals, the CD4 lymphocyte count ranges from 0.6-1.9x109/L).
* 4B most often occurs 7-10 years after infection. Skin lesions during this period are deeper in nature and tend to be protracted. Damage to internal organs begins to develop. Weight loss, fever, localized Kaposi's sarcoma, and damage to the peripheral nervous system may occur. Typically, stage 4B develops in patients with a CD4 count of 0.35-0.2x109/L.
* 4B is mainly detected 10-12 years after infection. It is characterized by the development of severe, life-threatening secondary diseases, their generalized nature, and damage to the central nervous system. Typically, stage 4B occurs when the CD4 count is less than 0.2x109/L.

Despite the fact that the transition of HIV infection to the stage of secondary diseases is a manifestation of the depletion of the protective reserves of the body of an infected person, this process is reversible (at least for some time). Spontaneously or as a result of therapy, the clinical manifestations of secondary diseases may disappear. Therefore, in the stage of secondary diseases, phases of progression (in the absence of antiretroviral therapy or against the background of antiretroviral therapy) and remission (spontaneous, after previously conducted antiretroviral therapy or against the background of antiretroviral therapy) are distinguished.

Stage 5– “terminal stage”, manifested by the irreversible course of secondary diseases. Even adequately administered antiretroviral therapy and treatment of secondary diseases are ineffective. As a result, the patient dies within a few months. At this stage, the CD4 cell count is usually below 0.05x109/L.

It should be noted that the clinical course of HIV infection is highly variable. The given data on the duration of individual stages of the disease are averaged and may have significant fluctuations.