Treatment of HIV / AIDS

The purpose of treatment for HIV infection is to maximize the patient's life and preserve its quality. Life expectancy without treatment in children is less than 6 months in 30% of cases, 75% of children survive to 6 years of age and up to 9 years of age to 50%.

It is necessary to conduct complex strictly individualized therapy of patients with HIV infection, with careful selection of antiretroviral drugs, timely treatment of secondary diseases. The treatment plan is constructed taking into account the stage of the pathological process and the age of the patients.

Treatment is carried out in three directions:

• impact on the virus with the help of antiretroviral drugs (etiotropic);
• chemoprophylaxis of opportunistic infections;
• treatment of secondary diseases.

At the heart of the appointment of antiretroviral drugs is the impact on the mechanisms of HIV replication, which are directly related to the life cycles of the virus.

Four classes of antiretroviral drugs are used that inhibit the replication of the virus at various stages of its life cycle. The first two classes include nucleoside and non-nucleoside reverse transcriptase inhibitors. These drugs disrupt the virus enzyme, reverse transcriptase, which converts HIV RNA to DNA. The third class includes protease inhibitors that act during the assembly of new viral particles, preventing the formation of full-fledged virions that can infect other host cells. Finally, the fourth class includes drugs that prevent the attachment of the virus to target cells-fusion inhibitors, interferons, interferon inducers-cycloferon (meglumine acridone acetate).

Monotherapy is used only as a chemoprophylaxis for transmission of the virus from the mother to the baby in the first 6 weeks of life. In this case, the chemoprophylaxis of a child born to an HIV-infected woman begins in the first 8-12 hours of life and is carried out with azidothymidine. The drug in the syrup is given internally at a dose of 2 mg / kg every 6 hours. If it is not possible to take inside, azidothymidine is administered intravenously at a rate of 1.6 mg / kg every 6 hours. Chemoprophylaxis can also be administered with nevirapine in the syrup for the first 72 hours of life, mg / kg (if the mother did not receive chemoprophylaxis during pregnancy and / or childbirth - with the first day).

In all other cases, in the treatment of HIV-infected children, combinations of antiretroviral drugs of various classes should be used. Preference is given to a combination of highly active (aggressive) therapy with three drugs, including various combinations of reverse transcriptase inhibitors and protease inhibitors.

Antiretroviral therapy is initiated with acute HIV infection in the manifest form, as well as in clinical manifestations of HIV infection (B, C and CDC categories) regardless of age and viral load.

In addition to the development of clinical symptoms, indications for prescribing therapy can be high or increasing levels of HIV RNA and a rapid decrease in the percentage of CD4 + T-lymphocytes to levels corresponding to moderate immunosuppression (2nd immune category, CDC). However, the level of HIV RNA, which could be considered an unconditional indication for the beginning of treatment, is not determined in young children.

The criterion for the effectiveness of therapy is an increase in CD4 + T-lymphocytes by at least 30% of the baseline level at 4 months from the start of therapy in patients who have not previously received antiretroviral drugs and a 10-fold decrease in viral load after 1-2 months of treatment. By 4 months, the viral load should decrease no less than 1000 times and by 6 months - to an undetectable level. With regard to clinical criteria for the effectiveness of treatment, due to the slow dynamics of HIV infection, the progression of the disease or the appearance of a secondary disease during the first 4-8 weeks of therapy is not always a sign of its inadequacy and can not be objective enough.

No less important task in the treatment of patients with HIV infection is the suppression of opportunistic (opportunistic) flora, which complicates the course of the underlying disease and threatens the life of the patient. For this purpose, antibacterial drugs are widely used, including various antibiotics, sulfonamides, and others.

To treat HIV infection, specific antiretroviral therapy is used. The goal of combined (highly active) antiretroviral therapy (HAART) of HIV infection is to suppress the virus replication to the undetectable level for the longest possible period, preserve or restore the immune system functions, and prevent the progression of the disease and the development of complications of HIV infection (opportunistic infections).

Correctly selected first scheme of therapy gives the best effect, and the child can be on it for many years. With improperly selected medications, there is a need to replace therapy. With each subsequent replacement of drugs, the effectiveness of antiretroviral therapy is reduced by 20-30%.

This is of particular importance in the treatment of HIV-infected children, since the amount of antiretroviral drugs in children's practice is limited.

Currently, there are the following main recommendations for the treatment of children with HIV in the world:

• "Recommendations on antiviral therapy for HIV infection in children" USA, Atlanta, CDC 24.03.2005;
• "Recommendations on antiviral therapy for HIV infection in children" PENTA, 2004 - European recommendations;
• "WHO Protocols for the CIS countries on providing care and treatment for HIV and AIDS", March 2004.

According to the experience of work, the most progressive of the above are American recommendations, based on the results of the most recent clinical studies. European recommendations summarize the experience in the treatment of HIV infection in children accumulated in European countries. Approaches to the tactics of HIV treatment in the American and European recommendations are very similar.

Absolute indications for the onset of HAART are the clinical manifestations of HIV infection and / or severe immunodeficiency.

When deciding on the use of specific therapy, the doctor must take into account the fact that HAART is prescribed to the child for life (continuous treatment), includes at least three drugs with a regimen 2-3 times a day. Therefore, HAART should be administered only according to the indications, taking into account the individual characteristics of each child and the course of HIV infection in each individual case.

Thus, HAART should be assigned to qualified specialists only on absolute indications, with the preparedness of the child's family for the initiation of therapy. The key to the success of antiretroviral therapy is the desire of parents to treat their child and strict compliance with their doctor's prescriptions.

Unreasonable prescription of HAART can significantly reduce a child's quality of life.

In children of the first year of life, the main criterion for prescribing therapy is the degree of immunosuppression. The level of viral load in infants is not an indication for the appointment of HAART.

The amount of HIV RNA in infants is significantly higher than in older children and adults, and the clinical manifestations of HIV infection may be quite scarce. The level of viral load of HIV is not a prognostic criterion for the course of the disease in children of the first year of life.

At the same time, severe immunodeficiency, regardless of the level of viral load, is a prognostically unfavorable sign and is an indication for the appointment of HAART.

Indications for HAART in children younger than 12 months (Guidelines for Antiretroviral Treatment of HIV Infection in Children, CDC 2005)

Clinical Categories	CD4 T lymphocytes	Viral load	Recommendations
Presence of symptoms (clinical categories A, B or C)	<25% (immunological category 2 and pi 3)	Any	Treat
Asymptomatic stage (category I)	> 25% (immunological category 1)	Any	The possibility of therapy

Indications for early HAART in children> 1 year

Clinical categories	CD4 T lymphocytes	Viral load	Recommendations
AIDS (clinical category C)	<15% (immunological category 2 or 3)	Any	Treat
Presence of symptoms (clinical categories A. B or C)	15% -25% (immunological category 2)	> 100,000 copies / ml	The possibility of therapy
Asymptomatic stage (category N)	> 25% (immunological category I)	<100,000 copies / ml	There is no need for therapy

In children older than 1 year with the appointment of HAART, in addition to the degree of immunosuppression, the level of viral load is also taken into account. According to the United States and Europe, the risk of developing AIDS and death during the year in this age group increases dramatically with a viral load of more than 100,000 copies / ml.

Combined antiviral therapy for children with HIV began to be carried out since 1997.

Drug therapy for HIV infection includes basic therapy (which is determined by the stage of the disease and the level of CD4 lymphocytes), as well as the treatment of secondary and concomitant diseases.

Currently, the main component of HIV treatment is antiretroviral therapy, with which it is possible to achieve a controlled course of the disease, that is, in spite of the impossibility of complete cure, it is possible to stop the progression of the disease. Antiretroviral therapy should be administered for life, a continuous course.

Conditions for prescribing HAART (PENTA guidance on antiretroviral therapy, 2004)

Infants

1. Clinical
   • Start all infants in stage B or C (AIDS) by CDC
2. Surrogate Markers
   • Starting all babies with CD4 <25-35%
   • It is recommended to start with a viral load> 1 million copies / ml

Children aged 1-3 pp

1. Clinical
   • Beginning with all children in stage C (AIDS)
2. Surrogate Markers
   • Start all children with CD4 <20%
   • It is recommended to start with a viral load> 250,000 copies / ml

Children aged 4-8 years

1. Clinical
   • Beginning with all children in stage C (AIDS)
2. Surrogate Markers
   • Start all children with CD4 <15%
   • It is recommended to start with a viral load> 250,000 copies / ml

Children aged 9-12 years

1. Clinical
   • Start all children and stage C (AIDS)
2. Surrogate Markers
   • Start all children with CD4 <15%
   • It is recommended to begin with a viral load> 250 000 copies / ml

Adolescents aged 13-17 years

1. Clinical
   • Beginning with all children in stage C (AIDS)
2. Surrogate Markers
   • Start all teenagers with CD4 abs. The amount of 200-350 cells / mm ³

During the treatment, surveys are conducted, the purpose of which is to monitor its effectiveness and safety. In a planned manner, these examinations are conducted 4 and 12 weeks after the start of treatment, then every 12 weeks.

The following groups of antiretroviral drugs are used:

1. Preparations blocking the process of reverse transcription (synthesis of viral DNA on the matrix of viral RNA) - inhibitors of reverse transcriptase, Among them, two groups of drugs are distinguished:
   • Nucleoside analogues (NRTIs) altered nucleoside molecules) embedded in the synthesized DNA chain and stopping its further assembly: azidothymidine (AZT), phosphazide (F-AZT), d4T, ddA, ZTS), abzkavir (ABC), combivir;
   • non-nucleoside analogues (NNRTIs) blocking the viral enzyme necessary for reverse transcription - reverse transcriptase: efavirenz (EFV), nevirapine (NVP).
2. Drugs that block the formation of full-fledged HIV proteins and, ultimately, the assembly of new viruses - HIV protease inhibitors (HIV): saquinanir (SQV), indinavir (IDV), nelfinavir (NFV), ritonavir (RTV), lopinavir / ritonavir (LPV / RTV).
3. Drugs that affect the receptors used by the virus to infiltrate HIV into the host cell are fusion inhibitors.

Many of these drugs are used in the form of different dosage forms (including those intended for the treatment of young children). In addition, combined preparations containing two or more drugs in one tablet (capsule) are registered.

The combination of two NRTIs is the basis of various antiretroviral therapy regimens.

For children, therapy regimens are recommended, including 2 NRTIs and 1 IP or 2 NRTIs and 1 NNI0T.

When choosing the optimal therapy regimen for a particular patient, the following is taken into account: the effectiveness and toxicity of the drugs, the possibility of combining them, the tolerability of the drugs by the patient, the convenience of taking medications - the brevity of intake, the combination of antiretroviral drugs with drugs that are (or may be) used for treatment the patient's secondary and associated diseases.

Clinical and laboratory criteria are used to evaluate the effectiveness of HAART.

Of the laboratory criteria for evaluating the effectiveness of treatment, the most informative is the level of CD4 lymphocyte and the concentration of HIV RNA.

With correctly selected HAART, the level of RNA-HIV is expected to decrease approximately 10-fold by 4-3 weeks after its initiation, and by 12-24 weeks of treatment it is below the detection level (below 400 or 50 copies per ml). The number of CD4 lymphocytes is also increased by 12-24 weeks from the onset of HAART.

Further, with effective HAART, the HIV RNA level should be below the detection level, but rises not exceeding 1000 copies / ml are possible. Neither the increase in the level of CD4-lymphocytes regress secondary diseases.

If HAART is ineffective and this is not related to disturbances in the regimen of taking the drug, taking antagonist medications, etc., it is recommended that a test for the resistance of the virus to drugs and the appointment of a new therapy regimen taking into account the results of this test be recommended.

Forecast

Very heavy. At clinically expressed forms the lethality is about 50%. From diagnosis to death, from 2-3 months to 2 years and more. In no case, normal immune functions are restored spontaneously or under the influence of treatment. Among the patients diagnosed before 1982, about 90% have died so far. However, recently there have been reports of a more favorable prognosis, especially in the case of HIV infection of the second type. Patients with Kaposi's sarcoma have a better prognosis than patients with opportunistic infections. There is an opinion that patients with Kaposi's sarcoma have less damage to the immune system.

Prognosis in children is more serious than in adults. Children die from opportunistic infections and rarely from Kaposi's sarcoma and other blastomas.