HIV infection and AIDS - Complications

Complications of HIV infection are secondary diseases that develop against the background of immunodeficiency. The mechanism of their occurrence is associated either with the suppression of cellular and humoral immunity (infectious diseases and tumors), or with the direct impact of the human immunodeficiency virus (for example, some neurological disorders).

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Mycobacteriosis

Approximately 65% of HIV-infected patients are diagnosed with tuberculosis as a newly developed disease, while the remaining patients have a reactivation of the process. HIV significantly affects the state of the immune system (and immunoreactivity) in tuberculosis, disrupts the differentiation of macrophages and prevents the formation of specific granuloma. While in the early stages of HIV infection the morphology of specific inflammation does not change significantly, at the AIDS stage granulomas simply do not form. A feature of pulmonary tuberculosis in HIV-infected patients is the severe course of the disease with damage to the bronchi and the formation of fistulas of the pleura, pericardium and lymph nodes. As a rule, in 75-100% of cases, pulmonary tuberculosis occurs in HIV-infected patients, however, as immunodeficiency increases, dissemination and the development of extrapulmonary forms of the disease are noted in 25-70% of patients. Tuberculosis is one of the main causes of death of patients (at the AIDS stage) in Ukraine. The processes occurring in the lungs of people with AIDS are the formation of root adenopathy and miliary rashes; the occurrence of predominantly interstitial changes and the formation of pleural effusion. At the same time, a decrease in the number of cases accompanied by the disintegration of lung tissue is noted, and, consequently, the number of patients in whose sputum mycobacteria are detected during microscopy and culture. The frequent development of tuberculous mycobacteriemia in AIDS patients is considered to be quite typical, usually complicated by septic shock and dysfunction of various organs. Often, lesions of the lymph nodes (especially the cervical), bones, central nervous system, meninges and digestive organs are observed: abscesses of the prostate and liver have been described. In approximately 60-80% of HIV-infected patients, tuberculosis occurs only with lung damage; in 30-40%, changes in other organs are detected.

The group of pathogens of "non-tuberculous" mycobacterioses consists of representatives of various species of mycobacteria (over forty). Eighteen varieties of mycobacteria cause diseases in humans. Four species of microorganisms have a relatively high pathogenicity for humans, and fourteen species are considered opportunistic. Atypical mycobacteriosis caused by M.avium (part of the M.avium complex - MAC) is a superinfection. It is a component of the group of AIDS-associated opportunistic infections. Before the HIV pandemic, atypical mycobacteriosis was diagnosed extremely rarely, usually in individuals with severe immunosuppression (for example, during organ and tissue transplantation, after long-term corticosteroid therapy, in cancer patients). Patients suffering from HIV infection sometimes develop a disseminated form of MAC infection. In the terminal stage, localized or generalized forms of the disease are recorded. In localized MAC infection, skin abscesses and lymph node lesions are detected, and in generalized infection, general intoxication and gastrointestinal syndromes, as well as extrabiliary obstruction syndrome, are detected. Signs of general intoxication syndrome are fever, asthenia, weight loss, severe anemia, leukopenia, and increased activity of alanine transaminase in the blood serum. In the gastrointestinal syndrome, chronic diarrhea and abdominal pain occur: hepatosplenomegaly, mesadenitis, and malabsorption syndrome are noted. Extrabiliary obstruction is caused by periportal and peripancreatic lymphadenitis, leading to biliary block and toxic hepatitis. The basis for diagnosing atypical mycobacterioses is the isolation of mycobacterium hemoculture.

Pneumocystis pneumonia

Previously, the causative agent of this disease was classified as a protozoan, but genetic and biochemical analysis of P. carinii showed its taxonomic affiliation with yeast fungi. There are three morphological forms of P. carinii - sporozoite (an intracystic body with a diameter of 1-2 μm). trophozoite (vegetative form), a cyst with a thick wall with a diameter of 7-10 μm (consists of eight pear-shaped sporozoites).

In nature, pneumocysts are found in rats, mice, dogs, cats, pigs, rabbits and other mammals, but human infection is possible only through contact with humans. Infection occurs through airborne, aerogenic, inhalation and transplacental (rare) routes. Pneumocysts have a high affinity for lung tissue, so even in fatal cases the pathological process rarely goes beyond the lungs (this is associated with the extremely low virulence of the pathogen). Microorganisms attach to pneumocytes, causing their desquamation. The main clinical signs of pneumocystosis are interstitial pneumonia and reactive alveolitis. Symptoms are nonspecific. The incubation period of pneumocystis pneumonia varies from 8-10 days to 5 weeks. The onset of the disease cannot be distinguished from common respiratory tract infections. Clinical symptoms in AIDS patients develop more slowly than in patients with hemoblastoses. Shortness of breath occurs very quickly (respiratory rate up to 30-50 per minute) and is accompanied by a dry or wet cough with scanty, viscous (sometimes foamy) sputum, cyanosis, and an increase in body temperature. Pleural pain and hemoptysis occur rarely. During auscultation, harsh or weakened breathing (locally or over the entire surface of the lungs) and dry wheezing are heard. As pneumonia progresses, symptoms of respiratory and cardiovascular failure may increase. The radiographic picture is nonspecific at first, then a hilar decrease in pneumatization of the lung tissue and an increase in the interstitial pattern are detected. In more than half of the cases, bilateral cloud-like infiltrates are visualized (the "butterfly" symptom), and at the height of the disease - abundant focal shadows ("cotton wool" lung). At the onset of the disease, a normal radiographic picture is found in a third of patients. Early involvement of the acini creates a picture of the so-called air bronchogram on radiographs (often mistakenly associated with interstitial damage). However, later on radiographs determine the predominantly parenchymatous nature of pneumonia. In 10-30% of cases, asymmetrical, usually upper lobe infiltrates are noted. When performing CT, peripheral infiltrates (sometimes with foci of decay), decreased transparency ("ground glass") and emphysematous areas are detected. Pneumothorax is the most common complication.

Blood tests reveal hypochromic anemia, leukocytosis (up to 50x10 ⁹ /l) and eosinophilia. Biochemical blood tests reveal increased LDH activity up to 700-800 IU/l. Determination of PaO ₂ reveals arterial hypoxemia. Detection of antibodies to P. carinii is a non-specific test; there are no culture methods. Therefore, the diagnosis is based on direct morphological visualization of pneumocysts in biological material using various methods (immunofluorescence, Romanovsky-Giemsa and Gram staining methods, use of Schiff reagent, etc.), and PCR diagnostics are also performed.

Open lung biopsy is performed in case of progressive course of the disease. Macroscopically during the operation the patient's lung looks enlarged, compacted, its consistency resembles rubber; bullous and emphysematous changes are noted, cavities of decay are detected. Intraalveolar foamy exudate, diffuse alveolar damage, epithelioid granulomas, desquamative interstitial pneumonitis, interstitial lymphoid infiltrates are histological changes in lung tissue in case of pneumocystis pneumonia. The survival rate of AIDS patients in case of pneumocystis pneumonia does not exceed 55%. The prognosis worsens significantly if treatment is started against the background of acute respiratory failure, severe hypoxia or leukopenia. Mortality due to pneumonia and acute respiratory failure in AIDS patients, according to various sources, ranges from 52.5 to 100%, and in case of mechanical ventilation - 58-100%.

Cytomegalovirus infection

Cytomegalovirus infection is usually latent. However, clinically expressed forms of the disease are sometimes diagnosed, caused by primary infection with cytomegalovirus, as well as reinfection or reactivation of the virus in the infected organism. Generalized cytomegalovirus infection, accompanied by the occurrence of clinical symptoms, occupies an important place in the structure of opportunistic diseases of HIV-infected patients. This pathology is recorded in 20-40% of AIDS patients who do not take antiretroviral drugs. Cytomegalovirus infection is the immediate cause of death in 10-20% of HIV-infected patients. The probability of occurrence and severity of cytomegalovirus infection are associated with the degree of immunosuppression. If the number of CD4+ lymphocytes in the blood is 100-200 cells per 1 μl, then manifest cytomegalovirus infection is diagnosed in 1.5% of HIV-infected people. With a decrease in the number of CD4+ lymphocytes to 50-100 cells per 1 μl, the probability of developing cytomegalovirus infection increases almost fourfold. With the total disappearance of CD4+ lymphocytes (less than 50 cells per 1 μl), the disease is registered in almost half of infected patients.

If the content of CD4+ lymphocytes in the blood is high enough (more than 200 cells in 1 μl), then the manifestation of cytomegalovirus infection is rare. This disease, as a rule, develops gradually, while precursor symptoms are detected. preceding the formation of pronounced organ disorders. In adults, a long-term wave-like fever of an irregular type with increases in body temperature above 38.5 ° C is noted. weakness, rapid fatigue, loss of appetite, significant weight loss; less often - sweating (mainly at night), arthralgia or myalgia. If the lungs are affected, these symptoms are supplemented by a gradually increasing dry cough or cough with scanty sputum. During autopsy of deceased patients suffering from cytomegalovirus damage to the respiratory organs, fibroatelectasis of the lungs with cysts and encapsulated abscesses is often found. The most severe symptom of cytomegalovirus infection is retinitis (diagnosed in 25-30% of patients). Patients complain of floating spots before the eyes, then there is a decrease in visual acuity. Loss of vision is irreversible, since this process develops as a result of inflammation and necrosis of the retina. Ophthalmoscopy reveals exudates and perivascular infiltrates on the retina. With cytomegalovirus esophagitis, the patient experiences pain behind the breastbone when swallowing. Endoscopy typically visualizes an extensive superficial ulcer of the mucous membrane of the esophagus or stomach. Histological methods make it possible to detect cytomegalovirus cells in a biopsy: the PCR method can determine the DNA of the virus. Cytomegalovirus infection can affect various organs of the digestive system, but colitis most often develops. The patient is bothered by abdominal pain, loose stools, weight loss and loss of appetite. Intestinal perforation is the most formidable complication. As possible clinical symptoms of cytomegalovirus infection are also diagnosed ascending myelitis and polyneuropathy (subacute course): encephalitis, characterized by dementia; cytomegalovirus hepatitis with simultaneous damage to the bile ducts and the development of sclerosing cholangitis; adrenalitis. manifested by severe weakness and decreased arterial pressure. Sometimes there is epididymitis, cervicitis, pancreatitis.

Specific vascular lesions, mainly of the microcirculatory bed and small-caliber vessels, are a morphological feature of the pathological process in cytomegalovirus infection. Laboratory tests are required to establish a clinical diagnosis of cytomegalovirus infection. Studies have shown that the presence of IgM antibodies (or high titers of IgG antibodies) in the patient's blood, as well as the presence of virions in saliva, urine, sperm, and vaginal secretions, are insufficient to establish the fact of active virus replication or to confirm the diagnosis of manifest cytomegalovirus infection. Detection of the virus (its antigens or DNA) in the blood has diagnostic value. The titer of cytomegalovirus DNA serves as a reliable criterion for high cytomegalovirus activity, proving its etiologic role in the development of certain clinical symptoms. With a 10-fold increase in the concentration of viral DNA in plasma, the likelihood of developing cytomegalovirus disease increases threefold. The detection of a high concentration of viral DNA in blood leukocytes and plasma requires immediate initiation of etiotropic therapy.

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Toxoplasmosis

Toxoplasmosis is a disease caused by T.gondii, which most often occurs in HIV-infected patients against the background of AIDS. When toxoplasma enters the human body, it leads to the formation of space-occupying lesions in the central nervous system (in 50-60% of cases) and the development of primary epileptic seizures (in 28% of cases). Toxoplasma is an intracellular parasite; humans become infected when eating foods (meat and vegetables) containing oocysts or tissue cysts. It is believed that the development of toxoplasmosis is a reactivation of a latent infection, since the presence of antibodies to toxoplasma in the blood serum increases the likelihood of toxoplasmosis by ten times. However, approximately 5% of HIV-infected patients do not have antibodies to T. gondii at the time of diagnosis of toxoplasmosis. Infection usually occurs in childhood. Cysts are foci of smoldering infection, the aggravation or relapse of which may occur several years or even decades after HIV infection. In the form of cysts, toxoplasma persists for up to 10-15 years, mainly in the tissues of the brain and visual organ, as well as in the internal organs. Pathomorphological changes in toxoplasmosis are of a phased nature. In the parasitemic phase, toxoplasma enters the regional lymph nodes, then penetrates the bloodstream and spreads throughout the organs and tissues. In the second phase, toxoplasma is fixed in the visceral organs, leading to the development of necrotic and inflammatory changes and the formation of small granulomas. During the third (final) stage, toxoplasma forms true cysts in the tissues; the inflammatory reaction disappears, and the foci of necrosis undergo calcification. Although toxoplasma can affect all organs and tissues, as a rule, the cerebral form of the disease is recorded in HIV-infected patients. Fever, headaches, the occurrence of various focal neurological symptoms in 90% of cases (hemiparesis, aphasia, mental and some other disorders) are noted. In the absence of adequate treatment, confusion, stupor, and coma are observed as a result of cerebral edema. When performing MRI or CT with contrast, multiple foci with annular enhancement and perifocal edema are detected, less often - a single focus. Differential diagnosis is carried out with brain lymphoma, tumors of other etiologies, AIDS-dementia syndrome, multifocal leukoencephalopathy and tuberculomas. In almost every case, a predominant lesion of certain organs and systems is diagnosed. Sometimes toxoplasmosis occurs without the formation of volumetric formations in the brain (like herpes encephalitis or meningoencephalitis). Extracerebral localizations of toxoplasmosis (for example, interstitial pneumonia, myocarditis, chorioretinitis and damage to the digestive system) in patients with AIDS are recorded in 1.5-2% of cases. The maximum number of foci of extracerebral localizations are detected during examination of the visual apparatus of the eye (approximately 50% of cases). Dissemination (at least two localizations) occurs in 11.5% of cases. Diagnosing toxoplasmosis is extremely difficult. Cerebrospinal fluid during spinal puncture may be intact. The diagnosis is made on the basis of the clinical picture, MRI or CT data, as well as the presence of antibodies to toxoplasma in the blood serum. A brain biopsy is performed if it is impossible to establish a correct diagnosis. During biopsy, inflammation with a necrotic zone located in the center is observed in the affected areas.

Kaposi's sarcoma

Kaposi's sarcoma is a multifocal vascular tumor affecting the skin, mucous membranes, and internal organs. The development of Kaposi's sarcoma is associated with the human herpes virus type 8, which was first discovered in the skin of a patient with this tumor. Unlike the endemic and classical variants of the disease, the epidemic form of sarcoma is registered only in HIV-infected patients (mainly in homosexuals). In the pathogenesis of Kaposi's sarcoma, the leading role is given not to the malignant degeneration of cells, but to the disruption of the production of cytokines that control cellular proliferation. Invasive growth is not typical for this tumor.

Histological examination of Kaposi's sarcoma reveals increased proliferation of spindle-shaped cells similar to endothelial and smooth muscle cells of blood vessels. Sarcoma in HIV-infected patients progresses differently. Some patients are diagnosed with a mild form of the disease, while others have a more severe form. The clinical signs of Kaposi's sarcoma are varied. Most often, lesions develop in the skin, lymph nodes, digestive system organs, and lungs. Tumor growth can lead to lymphatic edema of surrounding tissues. In 80% of cases, damage to internal organs is combined with involvement of the skin in the pathological process. In the initial stages of the disease, small raised red-purple nodes form on the skin or mucous membrane, often arising at the site of injury. Small dark spots or a yellowish rim (resembling bruises) are sometimes found around the nodular elements. The diagnosis of Kaposi's sarcoma is made taking into account histological data. Biopsy of the affected areas reveals proliferation of spindle-shaped cells, erythrocyte diapedesis, hemosiderin-containing macrophages, and inflammatory infiltrates. Dyspnea is the first sign of lung damage in Kaposi's sarcoma. Hemoptysis is sometimes observed. Chest X-rays reveal bilateral darkening in the lower lobes of the lungs, merging with the borders of the mediastinum and the contour of the diaphragm; enlargement of the hilar lymph nodes is often detected. Kaposi's sarcoma should be differentiated from lymphomas and mycobacterial infection, which occurs with skin lesions. In 50% of patients, damage to the digestive system is diagnosed, and in severe cases, intestinal obstruction or bleeding occurs. Involvement of the bile ducts in the pathological process leads to the development of mechanical jaundice.

Mortality and causes of death in HIV infection

Death of HIV-infected patients occurs either from the progression of secondary diseases or from any other concomitant diseases not related to HIV. Generalized tuberculosis is the main cause of death in AIDS patients. In addition, pulmonary pathology (with subsequent development of respiratory failure) and manifest cytomegalovirus infection are considered to be the cause of death. Recently, an increase in mortality due to liver cirrhosis caused by the development of viral hepatitis C against the background of chronic alcohol intoxication has been recorded. The progression of chronic hepatitis to cirrhosis in such patients occurs within 2-3 years.