HIV and AIDS

HIV infection is an infection caused by the human immunodeficiency virus infection ( HIV-infection). HIV infection is a slowly progressing anthroponotic disease with a contact transmission, characterized by the defeat of the immune system with the development of AIDS. Clinical manifestations of AIDS leading to the death of an infected person are opportunistic (secondary) infections, malignant neoplasms and autoimmune processes.

HIV infection is caused by one of two retroviruses (HIV-1 and HIV-2), which destroy CD4 + lymphocytes and disrupt the cellular immune response, thereby increasing the risk of certain infections and tumors. Initially, the infection may manifest as a nonspecific febrile fever. The likelihood of subsequent manifestations depends on the degree of immunodeficiency and is proportional to the level of CD4 + lymphocytes. Manifestations range from asymptomatic flow to acquired immunodeficiency syndrome (AIDS), which is manifested by severe opportunistic infections or tumors. Diagnosis of HIV infection is carried out by detecting antigens or antibodies. The goal of HIV treatment is to suppress HIV replication with a combination of drugs that inhibit the activity of the virus enzymes.

ICD-10 codes

• 820. Disease caused by the human immunodeficiency virus (HIV), manifested as infectious and parasitic diseases.
• 821. Disease caused by the human immunodeficiency virus (HIV), manifested as malignant neoplasms.
• 822. Disease caused by the human immunodeficiency virus (HIV), manifested as other specified diseases.
• 823. Disease caused by the human immunodeficiency virus (HIV), manifested as other conditions.
• 824. Disease caused by the human immunodeficiency virus (HIV), unspecified.
• Z21. Asymptomatic infectious status caused by the human immunodeficiency virus (HIV)

Epidemiology of HIV infection and AIDS

HIV is transmitted by contact with body fluids: blood, semen, vaginal secretions, breast milk, saliva that is separated from wounds or skin and mucous membrane damage that contain free virions or infected cells. Transmission of the virus is all the more likely, the higher the concentration of virions, which can be very high in primary HIV infection, even if it is asymptomatic. Transmission through saliva or droplets, formed by coughing and sneezing, is possible, but very unlikely. HIV is not transmitted through normal communication and even with close non-sexual contacts at work, at school, at home. Infection occurs with the direct transfer of physiological fluids during sexual intercourse, the use of blood-contaminated acute household items, in childbirth, breastfeeding, medical manipulation (blood transfusion, use of contaminated tools).

Some sexual methods, such as fellatio and cunnilingus, have a relatively low risk of transmission of the virus, but are not completely safe. The risk of HIV transmission is not significantly increased by swallowing sperm or vaginal secretions. However, if there are open wounds on the lips, the risk of HIV transmission increases. Sexual techniques that cause mucosal trauma (eg, sexual intercourse) have a very high risk. The highest risk of HIV transmission during anal sex. Inflammation of the mucous membranes promotes the transmission of the virus; STIs, such as gonorrhea, chlamydia, trichomoniasis, as well as those that cause ulceration of the mucous membranes (chancroid, herpes, syphilis), increase the risk of HIV transmission.

HIV is transmitted from mother to child transplacental or when passing through the birth canal in 30-50% of cases. HIV enters breast milk, and breastfeeding can transmit 75% of newborns at risk who have not been infected before.

The infection of a large number of women of childbearing age has led to an increase in AIDS cases in children.

The risk of HIV transmission after skin damage by a medical instrument contaminated with infected blood is on average 1/300 without special treatment; Urgent antiretroviral therapy probably reduces this risk to 1/1500. The risk of infection becomes higher if the wound is deep or if there is an inoculation of the blood (for example, using a contaminated needle). The risk of infection from infected medical personnel, provided that the appropriate measures to prevent the infection of patients are not fully understood, is however minimal. In the 1980s. One of the dentists infected HIV 6 or more of his patients in an unidentified way. However, extensive studies of patients treated with HIV-infected doctors, including surgeons, found several other reasons.

[1], [2], [3], [4], [5], [6], [7]

The risk of HIV transmission for various types of sexual activity

In the absence of wounds

The risk of HIV transmission is absent

• friendly kiss petting and massage
• use of individual sex devices
• (with masturbation partner, without sperm and vaginal secretions)
• joint bath and shower wash
• contact with intact skin of feces or urine

The theoretical very low risk of HIV transmission

In the presence of wounds

• wet kiss
• oral sex to a man (without / with ejaculation, without / with the ingestion of sperm)
• oral sex to a woman (without / with a barrier)
• oral-anal contact
• finger stimulation of the vagina or anus in or without a glove
• use of non-individual prodezin-infected sex devices

Low risk of HIV transmission

• vaginal or anal intercourse (with proper use of the condom)
• use of non-individual and non-disinfected sex devices

High risk of HIV transmission

• vaginal or anal intercourse (without / with ejaculation, without or with an incorrectly used condom)

Although donor screening has minimized the risk of transmission of the virus through blood transfusions, there is still a small risk, as screening tests may be negative in the early stages of HIV infection.

HIV is divided into two epidemiologically distinct groups. The first group includes predominantly male homosexuals and people who have come in contact with contaminated blood (intravenous drug users using non-sterile needles, blood recipients, before the introduction of effective donor screening methods). This group prevails in the US and Europe. In the second group heterosexual transmission of the virus prevails (the infection of men and women is approximately the same). 
 
This group prevails in Africa, South America and South Asia. In some countries (for example, Brazil, Thailand) there is no preferred way of transfer. In countries where heterosexual transmission predominates, HIV spreads through trade and transport routes, as well as economic migration routes, first to cities and only then to rural areas. In Africa, especially in southern Africa, the HIV epidemic has claimed the lives of millions of young people. The factors that predetermine this situation are poverty, poor education, an imperfect medical support system, and the lack of effective medicines.

Many opportunistic infections are the reactivation of latent infections, thus the epidemiological factors that cause the activation of latent diseases also increase the risk of developing specific opportunistic infections. Toxoplasmosis and tuberculosis are widespread in the general population in most developing countries, in the same way as coccidioidomycosis in the southwestern United States, and histoplasmosis in the Midwest. In the US and Europe, the herpes simplex virus type 8, which causes Kaposi's sarcoma, is common in male homosexual and bisexual men, but is virtually not found in other categories of HIV-infected people. For example, more than 90% of those infected with HIV in the US who developed Kaposi's sarcoma were at this risk.

What causes HIV and AIDS?

HIV infection is caused by retroviruses. Retroviruses are RNA-containing viruses, some of which cause disease in humans. They differ from other viruses by the mechanism of replication, by reverse transcription of copies of DNA, which are then built into the genome of the host cell.

Infection with human T-lymphotropic virus type 1 or 2 causes T-cell leukemias and lymphomas, lymphadenopathy, hepatosplenomegaly, skin damage and rarely immunodeficiency. Some of the patients with immunodeficiency develop infections similar to those that develop in AIDS. HTLV-1 can also cause myelopathy. HTLV-1 can be transmitted through sexual contact and through blood. In most cases, the virus is transmitted from mother to child with breastfeeding.

AIDS is an HIV infection that results in any of the disorders listed in categories B, C or a decrease in the number of CD4-pimphocytes (T-helpers) of less than 200 in 1 μl. Violations in categories B, C are severe opportunistic infections, certain tumors, such as Kaposi's sarcoma and non-Hodgkin's lymphoma, which are caused by a decrease in the cellular immune response, as well as pathology of the nervous system.

HIV-1 accounts for the majority of cases in the Western Hemisphere, Europe, Asia, Central, South and East Africa. HIV-2 is common in parts of West Africa and is less virulent than HIV-1. In some parts of West Africa, both types of the virus are common, as a result of which a person can be infected with HIV-1 and HIV-2 simultaneously.

HIV-1 first appeared among the peasants of Central Africa in the first half of the 20th century, when the virus circulating before only among the chimpanzee first struck a man. The global spread of the virus began in the late 1970s, and the diagnosis of AIDS was first raised in 1981. Currently, more than 40 million people are infected in the world. Every year, 3 million patients die, and every day 14,000 people become infected. 95% of people living with HIV live in developing countries, half of them women, and 1/7 - children under the age of 15.

What happens with HIV infection?

HIV binds and penetrates the host T-lymphocytes, interacting with CD4 molecules and chemokine receptors. After penetrating the host cell, RNA and the enzymes of the virus are activated. Viral replication begins with the synthesis of proviral DNA by reverse transcriptase, an RNA-dependent DNA polymerase. In the course of this copying, there are many errors caused by frequent mutations. The proviral DNA penetrates into the nucleus of the host cell and is integrated into its DNA. This process is called integration. With each cell division, the integrated proviral DNA is doubled along with the host cell DNA. Proviral DNA serves as the basis for transcription of viral RNA, as well as for the translation of viral proteins, including the glycoproteins of the viral envelope, dr 40 and dr120. Viral proteins collect into HIV virions on the inner side of the cell membrane, and then bud off from the cell. In each cell, thousands of virions are formed. Another enzyme of HIV protease - splits viral proteins, transforming the virion into an active form.

In affected CD4 lymphocytes, more than 98% of HIV virions circulating in plasma are formed. Population of infected CD4 + lymphocytes is the reservoir of the virus and causes the reactivation of HIV infection (for example, with the interruption of antiretroviral therapy). The half-life of virions from the plasma is about 6 hours. On average, with severe HIV infection, 10 ⁸ to 10 ⁹ virions are formed per day and are destroyed . Given the rapid replication of the virus, as well as the greater frequency of errors in reverse transcription caused by mutations, the risk of developing resistance to therapy and immune response increases.

The main consequence of HIV infection is the inhibition of the immune system, namely the loss of CD4 + T-lymphocytes, which cause cellular immunity and to a lesser extent, humoral immunity. The depletion of CD4 + lymphocytes is due to the direct cytotoxic effect of the virus, cellular immune cytotoxicity, and also damage to the thymus, resulting in decreased lymphocyte formation. The half-life of infected CD4 + lymphocytes is about 2 days. The level of decrease in CD4 + lymphocytes correlates with the viral load. For example, in the prodromal or in the period of primary HIV infection, the viral load is maximal (> 106 copies / ml), and accordingly the number of CD4 + lymphocytes rapidly decreases. The normal level of CD4 + lymphocytes is 750 cells / μl. To maintain an adequate immune response, the CD4 + lymphocyte level should be above 500 cells / μl.

The concentration of HIV virions in plasma stabilizes at a certain level (set point), which varies widely in different patients (on average, 4-5 1 10 / ml). It is determined by the method of amplification of nucleic acids and is recorded as the number of copies of HIV RNA in 1 ml of plasma. The higher the set point, the faster the level of CD4 + lymphocytes falls to those values at which immunity is impaired (<200 cells / μl) and, as a consequence, AIDS develops. With each increase in the viral load 3-fold (0.5 log ¹⁰ ) in patients not receiving antiretroviral therapy (APT), the risk of developing AIDS and death in the next 2-3 years increases by almost 50%, if not started by APT .

Also affects humoral immunity. In the lymph nodes, B cells (which produce antibodies) hyperplasticize, leading to lymphadenopathy and an increase in the synthesis of antibodies to previously known organism antigens, resulting in the development of hyperglobulinemia. The total number of antibodies (especially IgG and IgA), as well as the antibody titre against "old" antigens (for example, against cytomegalovirus) can be unusually high, while the reaction to "new antigens" is broken or nonexistent. The response to immune stimulation decreases along with a decrease in the level of CD4 + lymphocytes.

Antibodies to HIV can be detected several weeks after infection. At the same time, antibodies can not eliminate the infection due to the formation of mutant forms of HIV, which are not controlled by circulating antibodies in the body of the patient.

The risk and severity of opportunistic infections, AIDS and AIDS-associated tumors are determined by two factors: the level of CD4 + lymphocytes and the patient's sensitivity to potential opportunistic microorganisms. For example, the risk of developing pneumocystis pneumonia, toxoplasmosis encephalitis, cryptococcal meningitis occurs at a level of CD4 + lymphocytes of about 200 cells / μl, and the risk of infections caused by Mycobacterium avium or cytomegalovirus is at a level of 50 cells / μl. Without treatment, the risk of progression of HIV infection to AIDS is -2% per year in the first 2-3 years after infection, and 5-6% per year thereafter. In any case, AIDS develops.

HIV affects not only lymphocytes, but also dendritic skin cells, macrophages, microglia of the brain, cardiomyocytes, kidney cells, causing diseases in the corresponding systems. HIV virions in some systems, such as the nervous (brain and cerebrospinal fluid) and sex (sperm), are genetically different from those that circulate in the blood plasma. In these tissues, the concentration of the virus and its resistance may differ from those in the blood plasma.

What are the symptoms of HIV infection and AIDS?

Primary HIV infection can be asymptomatic or cause transient nonspecific symptoms of HIV infection (acute retroviral syndrome). Acute retroviral syndrome usually begins at the 1-4 th week after infection and lasts from 3 to 14 days. It occurs with fever, weakness, rash, arthralgia, generalized lymphadenopathy, and aseptic meningitis sometimes develops. These symptoms of HIV infection are often mistaken for infectious mononucleosis or nonspecific manifestations of symptoms of respiratory viral infection.

Most patients have a period of several months to several years, during which the symptoms of HIV infection are practically absent, they are mild, intermittent and nonspecific. These symptoms of HIV infection are subsequently explained when other manifestations of HIV or opportunistic infections develop. Most often develop asymptomatic generalized lymphadenopathy, oral cavity candidiasis, herpes zoster, diarrhea, weakness and fever. In some patients, depletion develops and progresses. Usually there is asymptomatic moderate cytopenia (leukopenia, anemia, thrombocytopenia).

Eventually, when the CD4 + lymphocyte count falls below 200 cells / mm3, the symptoms of HIV infection become more pronounced and one, and more often, one, AIDS-indicator disease develops (categories B, C in Table 192-1). Detection of infections caused by Mycobacterium spp, Pneumocystis jiroveci (formerly P. Carinn), Cryptococcus neoformans or other fungal infections is crucial. The remaining infections are nonspecific, but suggest the presence of AIDS due to unusual severity or recurrent course. These include: herpes zoster, herpes simplex, vaginal candidiasis, recurrent salmonella sepsis. Some patients develop tumors (eg, Kaposi's sarcoma, B-cell lymphomas) that occur more frequently, have a more severe course, or have an uncertain prognosis in HIV-infected patients. Some patients may have dysfunction of the nervous system.

Clinical groups of HIV infection

Category A

• Asymptomatic current
• Symptoms of acute primary HIV infection
• Persistent generalized lymphadenopathy
• Cryptosporidiosis, chronic gastrointestinal lesion (> 1 month)
• CMV infection (without lesions of the liver, spleen, lymph nodes)

Category B

• Bacterial angiomatosis
• Cytomegalovirus retinitis (with loss of vision)
• Oropharyngeal candidiasis
• Vulvovaginal candidiasis: persistent, frequent, poorly treatable
• Cervical dysplasia (moderate or severe) / cervical cancer in situ
• Common symptoms are fever> 38.5 ° C or diarrhea lasting more than 1 month
• Hairy leukoplakia of the mouth
• Herpes zoster - at least 2 proven episodes of infection or lesion of more than 1 dermatome
• Autoimmune thrombocytopenic purpura
• Listeriosis
• Inflammatory diseases of the pelvic organs, especially if complicated by a tubo-ovarian abscess
• Peripheral Neuropathy
• HIV-related encephalopathy
• Herpes simplex: chronic rashes (lasting more than 1 month) or bronchitis, pneumonitis, esophagitis
• Common or extrapulmonary histoplasmosis
• Isosporiasis (chronic gastrointestinal lesion> 1 month)
• Kaposi's Sarcoma
• Burkitt's lymphoma
• Immunoblastic lymphoma
• Primary CNS lymphoma
• Common or extrapulmonary lesions caused by Mycobacterium avium or Mycobacterium kansasii
• Pulmonary and extrapulmonary diseases caused by Mycobacterium tuberculosis
• Common or extrapulmonary damage caused by Mycobacterium of other species or unspecified species

Category C

• Candidiasis of bronchi, trachea, lungs
• Candidiasis of the esophagus
• Invasive cervical cancer
• Common or extrapulmonary coccidioidomycosis
• Extrapulmonary cryptococcosis
• Pneumonia caused by Pneumocystis proved (before P. Carinii)
• Recurrent pneumonia
• Progressive multifocal leukoencephalopathy
• Recurrent salmonella septicemia
• Toxoplasmosis of the brain
• Cachexy caused by HIV

The most frequent neurologic syndromes in HIV infection

• AIDS-dementia
• Cryptococcal meningitis
• Cytomegalovirus encephalitis
• Primary CNS lymphoma
• Progressive multifocal leukoencephalopathy
• Tuberculous meningitis or focal encephalitis
• Toxoplasmic encephalitis

[8], [9], [10], [11], [12], [13], [14], [15], [16]

Tumors often found in HIV-infected patients

Kaposi's sarcoma, non-Hodgkin's lymphoma, cervical cancer are AIDS-indicator tumors in HIV-infected patients. Other tumors: Hodgkin's lymphoma (especially mixed-cell and lymphopenic subtypes), primary CNS lymphoma, anal cancer, testicular cancer, melanoma and other skin tumors, lung cancer occur more frequently and are more severe. Leiomyosarcoma is a rare complication of HIV infection in children.

Non-Hodgkin's Lymphoma

The incidence of non-Hodgkin's lymphoma in HIV-infected patients increases 50 to 200 times. Most of them are B-cell aggressive histologically highly differentiated lymphomas. In this disease, extranodal structures such as red bone marrow, gastrointestinal tract and other organs that are rarely affected by non-HIV-associated non-Hodgkin's lymphoma are involved in the process, the central nervous system and the body cavity (pleural, pericardial and abdominal).

Typically, the disease manifests itself by a rapid increase in lymph nodes or extranodal formations or systemic manifestations, such as weight loss, night sweats and fever. Diagnosis is established by biopsy with histological and immunochemical examination of tumor cells. Abnormal lymphocytes in the blood or unexplained cytopenia indicate the involvement of the red marrow in the process and require a biopsy. Determining the stage of the tumor may require the study of CSF, as well as CT or MRI of the chest, abdominal cavity and all other localizations where a tumor is suspected. The prognosis is poor for CD4 + lymphocytes <100 cells / μl, age over 35 years, poor functional state, red bone marrow affection, opportunistic infections in the history and highly differentiated histological subtype of lymphoma.

Non-Hodgkin's lymphoma is treated with systemic polychemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone), usually in combination with antiretroviral drugs, blood growth factors, prophylactic antibiotics and antifungal agents. Therapy may be limited to the development of severe myelosuppression, especially when a combination of myelosuppressive antitumor drugs and antiretroviral drugs is used. Another possible option is the use of intravenously anti-CD20 monoclonal antibodies (rituximab), which are effective in treating non-Hodgkin's lymphoma in patients without HIV infection. Radiation therapy reduces the size of large tumors and reduces pain and bleeding probability.

Primary lymphoma of the central nervous system

Primary CNS lymphomas develop in HIV-infected patients at a higher frequency than in the general population. The tumor consists of moderately and highly differentiated malignant B cells derived from CNS tissue. It is manifested by the following symptoms: headache, epileptic seizures, neurological defects (paralysis of the cranial nerves), change in mental status.

Urgent therapy includes the prevention of cerebral edema and radiation therapy of the brain. A tumor is usually sensitive to radiation therapy, but the average life expectancy does not exceed 6 months. The role of anti-tumor chemotherapy is unknown. Life expectancy increases with the use of HAART.

Cervical cancer

Cervical cancer in HIV-infected patients is difficult to treat. In HIV-infected women, the incidence of human papillomavirus is increased, the persistence of its oncogenic subtypes (types 16, 18, 31, 33, 35 and 39), as well as intraepithelial dysplasia of the cervix (60%), but they do not a significant increase in the incidence of cervical cancer. Cervical cancer in these women is more severe, more difficult to treat and has a higher incidence of relapse after recovery. The commonly recognized risk factors for HIV-infected patients are: infection with human papillomavirus subtypes 16 or 18, the number of CD4 + lymphocytes <200 cells / μl, age over 34 years. HIV infection does not worsen the course of VIDM and cervical cancer. To control the progression of the process it is important to often take smears on Papanicolaou. Carrying out HAART can cause the cessation of papillomavirus infection, regression of VDSM, its effect in cervical cancer has not been studied.

[17], [18], [19], [20], [21], [22], [23]

Squamous cell carcinoma of the anus and vulva

Squamous cell carcinoma of the anus and vulva is caused by human papillomavirus and is more common in HIV-infected patients. The reason for the high frequency of this pathology in HIV-infected patients is the frequent occurrence of high-risk behaviors among them, that is, anal intercourse, and not HIV itself. Often there is anal dysplasia, against which squamous cell carcinoma of the anus can be very aggressive. Treatment includes surgical extirpation of the tumor, radiotherapy, combined modal chemotherapy with mitomycin or cisplatin in combination with 5-fluorouracil.

How is HIV and AIDS diagnosed?

Screening tests for HIV (for detecting antibodies) are periodically recommended to people at risk. People from the very high risk group, especially sexually active, having many sexual partners and not practicing safe sex, should be examined every 6 months. This survey is anonymous, available and most often free of charge in many public and private institutions around the world.

HIV infection is suspected in patients with persistent unexplained generalized lymphadenopathy or in the presence of any of the conditions listed in categories B or C. It should also be suspected of HIV infection in high-risk patients if they have nonspecific symptoms that may be a manifestation of acute primary HIV infection. After the diagnosis of HIV infection should be determined stage of the disease by the level of viral load in the blood plasma and the number of CD4 + lymphocytes. The level of CD4 + lymphocytes is calculated based on the number of leukocytes, the percentage of lymphocytes and the percentage of lymphocytes that have CD4. The normal level of CD4 + lymphocytes in adults is 750 ± 250 cells / μl. Determination of antibodies to HIV is a sensitive and specific test, with the exception of the first few weeks after infection. Enzyme-linked immunosorbent assay (ELISA) -analysis for antibodies to HIV-is highly sensitive, but it can sometimes give false positive results. That is why the positive result of the ELISA test should be confirmed by such a more specific test as Western blotting. New rapid tests for blood and saliva are performed quickly, do not require technically complicated manipulations and equipment, and also allow testing under various conditions and immediately inform the patient of the result. The positive results of these tests should be confirmed by standard blood tests.

If HIV infection is likely despite the absence of antibodies in the blood (within the first few weeks after infection), plasma can be tested for HIV RNA. The tests based on the amplification of nucleic acids are sensitive and specific. The detection of HIV-antigen p24 by ELISA is less specific and sensitive than the direct determination of HIV in the blood. Determining the concentration of HIV RNA (virions) requires such complex methods as reverse transcriptional PCR (RT-PCR) or a brush DNA test that is sensitive to very low levels of HIV RNA. The quantitative determination of HIV RNA in plasma is used to determine the prognosis and control the effectiveness of treatment. The level of HIV in the plasma or the viral load reflects replication activity. A high level of set point (a relatively stable level of viral load, remaining at the same level as in the primary infection) indicates a high risk of a decrease in CD4 + lymphocyte count and development of opportunistic infections even in patients without clinical manifestations, as well as in immunocompetent patients (patients with CD4 + lymphocyte count> 500 cells / μl).

HIV infection is divided at the stage on the basis of clinical manifestations (in order of increasing severity - categories A, B, C) and the number of CD4 + lymphocytes (> 500, 200-499, <200 cells / μl). The clinical category is set according to the most severe condition that the patient had or is experiencing. Thus, the patient can not be transferred to a lower clinical category.

Diagnosis of various opportunistic infections, tumors and other syndromes developing in HIV-infected patients is described in most guidelines. Most of the issues unique to HIV infection.

Hematologic disorders occur frequently, and therefore puncture and biopsy of the red bone marrow can be very useful in explaining some syndromes (eg, cytopenia, lymphoma, cancer). They also help in the diagnosis of disseminated infections caused by MAC, Mycobacterium tuberculosis, Criptococcus, Histoplasma, human parvovirus B19, Pneumocystis jiroveci (formerly P. Carinii), Leishmania. In most patients, the red bone marrow is normal regenerative or hyperregenerative, despite peripheral cytopenia, which reflects the peripheral destruction of blood cells. The level of iron is usually normal or elevated and reflects the anemia of a chronic disease (a violation of the reutilization of iron). Usually there are light or moderate plasmacytosis, lymphoid aggregates, a large number of histiocytes, dysplastic changes in the hematopoietic cells.
The diagnosis of HIV-associated neurological syndromes often requires CT with contrast or MRI. 

How is HIV and AIDS treated?

The goal of HAART is to suppress viral replication as much as possible. Complete suppression of replication to undetectable levels is possible, provided that patients will take drugs> 95% of the time. However, it is difficult to achieve such a degree of compliance. Partial suppression of replication (failure to reduce plasma HIV RNA level to undetectable levels) indicates the stability of HIV and the high probability of ineffectiveness of subsequent treatment. After the onset of HAART, a part of the patients deteriorate their clinical state, despite the increase in the number of CD4 + lymphocytes. This is due to the reaction of the immune system to subclinical pre-existing opportunistic infections or to the antigens of microorganisms that have remained after their successful cure. These reactions can be expressed and are called inflammatory syndromes of immune regeneration (IRIS).

The effectiveness of HAART is estimated by the level of viral RNA in plasma after 4-8 weeks in the first months, and then in 3-4 months. With successful therapy, HIV RNA ceases to be detected within 3-6 months. The increase in viral load is the earliest sign of treatment failure. If the treatment is ineffective by studying the sensitivity (resistance) to the drugs, the sensitivity of the dominant HIV variant to all available drugs can be established to adequately correct the treatment.

An increase in the number of patients receiving inadequate treatment regimens promotes the formation of mutant forms of HIV, which have a higher resistance to drugs, but are similar to wild type HIV and show less ability to reduce CD4 + lymphocyte levels.

Preparations of three out of five classes inhibit reverse transcriptase, blocking its RNA-dependent or DNA-dependent polymerase activity. Nucleoside reverse transcriptase inhibitors (NRTIs) are phosphorylated and converted to active metabolites that compete for inclusion in viral DNA. They competitively inhibit HIV reverse transcriptase and stop the synthesis of DNA chains. Nucleotide reverse transcriptase inhibitors inhibit it just like nucleoside, but, unlike the latter, do not require prior phosphorylation. Non-nucleoside reverse transcriptase inhibitors bind directly to the enzyme itself. Protease inhibitors inhibit the viral protease, which is critical for the maturation of HIV daughter virions upon exit from the host cell. Inhibitors of fusion block the binding of HIV to the CD4 + -lymphocyte receptors, which is necessary for the penetration of the virus into the cells.

To completely suppress the replication of wild HIV, a combination of 3-4 drugs of different classes is usually needed. Antiretroviral therapy is selected taking into account the concomitant diseases (for example, a violation of the liver function) and other medications used by the patient (to prevent drug interactions). To achieve the maximum agreement between the doctor and the patient, it is necessary to use available and well tolerated regimens of therapy, as well as to apply the drugs 1 time per day (preferably) or 2 times. The recommendations of experts on the initiation, selection, replacement and discontinuation of therapy, as well as the specific treatment of women and children, are regularly updated and presented on the website www. Aidsinfo. Nih. Gov / guidelines.
With the interaction of antiretroviral drugs with each other, their effectiveness can synergistically increase. For example, a subtherapeutic dose of ritonavir (100 mg) can be combined with any other drug from the class of protease inhibitors (lopinavir, amprenavir, indinavir, atazonavir, tipronavir). Ritonavir inhibits the activity of hepatic enzymes that metabolize other protease inhibitors, thereby increasing the concentration and effectiveness of the latter. Another example is the combination of lamivudine (ZTS) and zidovudine (ZDV). With the use of these drugs in the form of monotherapy, resistance develops rapidly. However, a mutation that causes the development of resistance in response to the use of ZTS, simultaneously increases the sensitivity of HIV to HFA. Thus, these two drugs are synergists.

However, the interaction between antiretroviral drugs can lead to a decrease in the effectiveness of each of them. One of the drugs can accelerate the excretion of another (by inducing hepatic enzymes of the cytochrome P-450 system responsible for elimination). The second, poorly understood mechanism of interaction of some NRTI (zidovudine and stavudine) is a decrease in antiviral activity without accelerating the elimination of the drug.

Combination of drugs often increases the risk of side effects, compared to monotherapy with the same drugs. One of the possible reasons for this is the metabolism of protease inhibitor class drugs in the liver in the cytochrome P-450 system, as a result of which the metabolism (and, correspondingly, the concentration) of other drugs is inhibited. Another mechanism is to summarize the toxicity of drugs: the combination of such NRTIs as d4T and ddl increases the likelihood of developing unwanted metabolic effects and peripheral neuropathy. Given that enough medications can interact with antiretroviral drugs, it is always necessary to check their compatibility before starting a new drug. In addition, it should be said that grapefruit juice and the decoction of St. John's wort reduce the activity of some antiretroviral drugs, and therefore should be excluded.

Side effects: severe anemia, pancreatitis, hepatitis, impaired glucose tolerance - can be detected in blood tests before the appearance of the first clinical manifestations. Patients should be monitored regularly (clinically and with appropriate laboratory tests, especially with the appointment of a new drug or the appearance of incomprehensible symptoms.

Metabolic disorders include interconnected syndromes of fat redistribution, hyperlipidemia and insulin resistance. Quite often a redistribution of subcutaneous fat from the face and distal segments of the limbs on the trunk and abdomen is developing. This leads to disfigurement and the development of stress in patients. Cosmetic therapy with the injection of collagen or polyactic acid has a beneficial effect. Hyperlipidemia and hyperglycemia due to insulin resistance, as well as non-alcoholic steatohepatitis can be accompanied by lipodystrophy. Preparations of all classes are capable of causing these metabolic disturbances. Some drugs, such as ritonavir or d4T, usually increase lipid levels, while others, such as atazanavir, have minimal effect on their level.

There are probably many mechanisms that lead to metabolic disorders. One of them is mitochondrial toxicity. The risk of development of mitochondrial toxicity and, accordingly, metabolic disturbances varies depending on the class of the drug (the highest in NRTI and PI), and also within each class: for example, among NRTI, the highest risk is with d4T. These disorders are dose-dependent and occur usually in the first 1-2 years of treatment. Remote disorders and optimal therapy of metabolic disorders have not been studied. You can use lipid-lowering drugs (statins) and drugs that increase the sensitivity of cells to insulin (glitazones).

Bony complications of HAART include asymptomatic osteopenia and osteoporosis, which are common among patients with metabolic disorders. Rarely develops avascular necrosis of large joints (hip, shoulder), accompanied by severe pain and joint dysfunction. The causes of bone complications are poorly understood.

Interruption of HAART is relatively safe, provided that all drugs are canceled simultaneously. Discontinuation of therapy may be necessary for surgical treatment, as well as when drug toxicity can not be treated or it is necessary to eliminate it. After the interruption of therapy to establish a toxic drug, the same medicines are prescribed as monotherapy for several days, which is safe for most drugs. An exception is abacavir: in patients who have fever and rash on primary administration of abacavir, severe and even potentially lethal hypersensitivity reactions may occur if it is repeated.

Lifetime care

Despite the fact that due to new methods of treatment, the hopes of HIV-infected people for survival have significantly increased, the condition of many patients worsened and they died. Death in HIV infection is rarely sudden. Patients usually have time to think about their intentions. Despite this, the intentions should be recorded as early as possible in the form of a long-term power of attorney for treatment with clear instructions for lifelong care. All legal documents, including powers of attorney and will, must be in place. These documents are especially important for homosexual patients because of the complete lack of protection of inheritance rights and other rights (including visits and decision-making) of the partner.

When patients are at death, doctors should prescribe pain medication, drugs that relieve anorexia, fear and all other symptoms of stress. Significant weight loss in patients in the late stages of AIDS makes good skin care especially important. Comprehensive support for hospices is a good option for people dying from AIDS. However, until now hospices are supported only by individual donations and the help of all those who only want and can help, so their support is still at home.

How is HIV and AIDS prevented?

HIV vaccines are very difficult to develop because of the high variability of HIV surface proteins, which provides a wide variety of antigenic HIV variants. Despite this, a large number of potential vaccines are at different stages of research into the ability to prevent or improve the course of infection.

Prevention of HIV transmission

Education of people is a very effective measure. It significantly reduced the prevalence of infection in some countries of the world, especially in Thailand and Uganda. Given that sexual contact in most cases is the cause of infection, training aimed at eliminating the practice of unsafe sex is the most appropriate measure. Even if it is known that both partners are not HIV-infected and have never changed each other, safe sex is still mandatory. Condoms provide the best protection, but oil lubricants can damage latex, increasing the risk of a condom break. APT of HIV-infected patients reduces the risk of sexual transmission of the virus, but the degree of reduction is unknown.

Safe sex remains appropriate for the protection of both the HIV-infected people themselves and their partners. For example, unprotected sex between HIV-infected people can lead to the transmission of a resistant or more virulent HIV strain, as well as other viruses (CMV, Epstein-Barr virus, HSV, hepatitis B virus) that cause severe illness in AIDS patients.

Drug users who use intravenous drugs should be warned about the risk of using non-sterile needles and syringes. Prevention may be more effective in combination with the provision of sterile needles and syringes, drug dependence treatment and rehabilitation.

Anonymous research on HIV infection with the possibility of consulting a specialist before or after the test should be available to all comers. Pregnant women, whose test result was positive, explains the risk of transmission of the virus from mother to the fetus. The risk is reduced by 2/3 when using ZDV monotherapy or nevirapine, and perhaps even more when using a combination of 2-3 drugs. Treatment can be toxic to the mother or fetus and can not be guaranteed to prevent the transmission of the virus. Some women prefer to interrupt their pregnancy for these or other reasons.

In countries of the world where donor blood and organs undergo a worldwide screening using modern methods (ELISA), the risk of HIV transmission during blood transfusion is probably between 1: 10,000 and 1: 100,000 transfusions. Transmission is still possible, because tests for detecting antibodies can be false-negative at the onset of infection. At present, screening of the blood for the detection of both antibodies and p24 antigen is introduced in the US and, possibly, further reduces the risk of transmission of the virus. To further reduce the risk of HIV transmission for people with risk factors for HIV infection, even those who have not yet detected antibodies to HIV in the blood, they are asked not to become donors of blood and organs.

To prevent the transmission of HIV from patients, medical workers should wear gloves in situations in which contact with the mucous membranes or body fluids of the patient is possible, and also how to prevent pricks and cuts. Social workers caring for patients at home should wear gloves if there is a possibility of contact with biological fluids. Surfaces or tools contaminated with blood or other body fluids should be rinsed and disinfected. Effective disinfectants are: heating, peroxides, alcohols, phenols, hypochlorite (bleach). Isolation of HIV-infected patients is not needed, except when this is indicated by opportunistic infections (eg tuberculosis) that have developed. An agreement providing measures to prevent the transmission of the virus from HIV-infected medical workers to patients has not yet been achieved.

Postexposure prophylaxis of HIV infection

Preventive treatment of HIV infection is indicated in case of penetrating wounds with HIV-infected blood wound (usually with stinging objects) or with massive contact of HIV-infected blood with mucous membranes (eyes, mouth). The risk of infection due to skin damage exceeds 0.3%, and after contact with mucous membranes is about 0.09%. The risk proportionally increases depending on the amount of biological material (higher with visible contamination of objects, damage by hollow sharp objects), the depth of damage and the viral load in the blood that has fallen. At present, a combination of 2 NRTIs (ZDV and 3TC) or 3 drugs (NRTI + PI or NNRTI) is recommended to reduce the risk of infection; nevirapine is not used because it causes hepatitis (rarely but with severe course)) for 1 month. The choice of combination depends on the degree of risk caused by the type of contact. Monotherapy ZDV, possibly, reduces the risk of transmission of the virus after injuries by sharp objects by about 80%, although there is no conclusive evidence of this.

Prevention of opportunistic infections

Effective chemoprophylaxis of HIV infection is available for many opportunistic infections. It reduces the incidence of diseases caused by P. Jiroveci, Candida, Cryptococcus and MAC. In patients with immune revival against the background of therapy, by reducing the amount of CD4 + lymphocytes above the threshold values> 3 months, prevention can be stopped.

Patients with a CD4 + lymphocyte count of <200 cells / μl should undergo primary prevention against pneumonia caused by P. Jiroveci and toxoplasmosis encephalitis. To do this, a combined preparation containing trimethoprim and sulfamethoxazole, every day or 3 times a week is used with high efficiency. Side effects can be minimized by applying the drug 3 times a week or gradually increasing the dose. Some patients who do not tolerate trimethoprim-sulfamethoxazole tolerate dapsone (100 mg once a day). For a small fraction of patients who have developed side effects (fever, neutropenia, rash) that are disturbing during their treatment, pentamidine (300 mg once a day) or atovaquone (1500 mg once a day) can be used.

Patients with a CD4 + lymphocyte count of <75 cells / μl should receive primary prophylaxis against MAC dissemination with azithromycin, clarithromycin, or rifabutin. Azithromycin is more preferable, since it can be given in the form of two 600-mg tablets per week, providing protection (70%) comparable to that provided daily by clarithromycin. In addition, it does not interact with other drugs. Patients with suspected latent tuberculosis (for any number of CD4 + lymphocytes) should be treated with rifampicin or rifabutin with pyrazinamide for 2 months daily, or with isoniazid for 9 months daily to prevent reactivation of the process.

For the primary prevention of fungal infections (esophageal candidiasis, cryptococcal meningitis and pneumonia), fluconazole is used per os daily (100-200 mg once a day) or weekly (400 mg). However, it should not be used often due to the high cost of the preventive course, good diagnosis and treatment of this pathology.

Secondary prophylaxis with fluconazole is given to patients if they develop oral, vaginal or esophageal candidiasis or cryptococcal infections. The transferred histoplasmosis is an indication for the prevention of itraconazole. Patients with latent toxoplasmosis, with the presence of serum antibodies (IgG) to Toxoplasma gondii, are prescribed trimethoprim-sulfamethoxazole (in the same doses as for pneumocystis pneumonia) to prevent reactivation of the process and subsequent toxoplasmosis encephalitis. Latent infection in the US is less common (about 15% of adults) compared with Europe and the most developed countries. Secondary prophylaxis is also indicated for patients with previous pneumocystis pneumonia, HSV infection and possibly aspergillosis.

What is the prognosis of HIV infection and AIDS?

As mentioned above, the risk of developing AIDS and / or death is predetermined by the number of CD4 + lymphocytes in the short term and the level of HIV RNA in blood plasma in the long-term. For every three-fold (0.5 log10) increase in viral load, mortality increases by 50% over the next 2-3 years. If HIV infection is effectively treated, this leads to an increase in the number of CD4 + lymphocytes, and the plasma HIV RNA level falls very quickly. HIV-associated morbidity and mortality are unique with CD4 + lymphocyte count> 500 cells / μl, low at 200-499 cells / μl, moderate at 50-200 cells / μl and high when CD4 + lymphocytes fall to less than 50 in 1 μl.

Since adequate antiviral therapy for HIV infection can cause pronounced and long-term side effects, it should not be administered to all patients. Current indications for initiating antiviral therapy for HIV infection: the number of CD4 + lymphocytes is <350 cells / μl and plasma HIV RNA levels> 55,000 copies / ml. The use of conventional combinations of antiretroviral drugs for the treatment of HIV infection (highly active antiretroviral therapy - HAART) is aimed at reducing plasma HIV RNA levels and increasing the number of CD4 + lymphocytes (immune regeneration or recovery). Reducing the number of CD4 + lymphocytes and increasing the level of HIV RNA in comparison with these parameters before treatment reduces the likelihood of the effectiveness of the prescribed therapy. However, some improvement is possible in patients with severe immunosuppression. An increase in the number of CD4 + lymphocytes means a corresponding reduction in the risk of developing opportunistic infections, other complications and death. With the restoration of immunity, the course of even those conditions that are not specifically treated (for example, HIV-induced cognitive dysfunction), or those previously recognized as incurable (for example, progressive multifocal leukoencephalopathy) may improve. The prognosis of tumors (for example, lymphoma, Kaposi's sarcoma) and opportunistic infections is also improving. Vaccines that could increase immunity to HIV in infected patients have been studied for many years, but they are still ineffective.