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 inhibition of cellular and humoral immunity (infectious diseases and tumors) or with direct exposure to the human immunodeficiency virus (eg, certain neurological disorders).

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

Mycobacteriosis

Approximately 65% of patients with HIV infection are diagnosed with tuberculosis as a newly diagnosed disease, the rest of patients are found to reactivate the process. HIV significantly affects the immune system (and immuno-reactivity) in tuberculosis, disrupts the differentiation of macrophages and prevents the formation of a specific granuloma. While in the early stages of HIV infection the morphology of the specific inflammation does not change significantly, at the AIDS stage the granulomas are simply not formed. The peculiarity of pulmonary tuberculosis in patients with HIV infection is a severe course of the disease with bronchial involvement and the formation of pleural fistula, pericardium and lymph nodes. Typically, in 75-100% of cases in patients with HIV infection there is a pulmonary form of tuberculosis, however, as the increase in immunodeficiency, in 25-70% of patients noted dissemination and the development of extrapulmonary forms of the disease. Tuberculosis is one of the main causes of death of patients (at the stage of AIDS) in Ukraine. The processes occurring in the lungs of people with AIDS are the formation of root adenopathy and miliary rashes; the appearance 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 the pulmonary tissue and, consequently, the number of patients in whose sputum microscopy and culture are detected by mycobacteria of tuberculosis are noted. Very characteristic is the frequent development of tuberculous mycobacteria in AIDS patients, usually complicated by septic shock and impaired functions of various organs. Often observed defeat of lymph nodes (especially cervical), bones, CNS, meninges and organs of the digestive system: described abscesses of the prostate and liver. Approximately 60-80% of HIV-infected patients have tuberculosis only with lung damage, 30-40% reveal changes in other organs.

A group of pathogens of "non-tubercular" mycobacteriosis consists of representatives of various species of mycobacteria (over forty). Eighteen varieties of mycobacteria cause diseases in humans. Four types of microorganisms have a relatively high pathogenicity for humans, and fourteen species are considered opportunistic. Atypical mycobacteriosis caused by M. avium (included in the complex M. avium complex - MAC), - superinfection. A group of AIDS-associated opportunistic infections. Prior to the HIV pandemic, atypical mycobacteriosis was rarely diagnosed, as a rule, in persons with severe immunosuppression (for example, organ and tissue transplantation, after prolonged corticosteroid therapy, in cancer patients). Patients suffering from HIV infection sometimes develop a disseminated form of MAC infection. In the terminal stage, a localized or generalized form of the disease is recorded. With localized MAC infection, abscesses of the skin and lesions of the lymph nodes are detected, and in the generalized case, general intestinal and gastrointestinal syndromes, as well as extrabiliary obstruction syndrome. Signs of general toxication syndrome - fever, asthenia, weight loss, severe anemia, leukopenia, increased activity of alanine transaminase in the blood serum. In the gastrointestinal syndrome there is chronic diarrhea, abdominal pain: note hepatosplenomegaly, mesadenitis and malabsorption syndrome. Extrabiliary obstruction is caused by periportal and peripancreatic lymphadenitis, leading to a biliary block and toxic hepatitis. The basis for diagnosing atypical mycobacteriosis is considered to be the release of mycobacterium blood culture.

Pneumocystis pneumonia

Earlier, the causative agent of this disease was referred to as the simplest, but the genetic and biochemical analysis of P. Carinii showed its taxonomic affiliation to yeast fungi. There are three morphological forms of P. Carinii - sporozoite (intracystic body with a diameter of 1-2 μm). Trophozoite (vegetative form), cyst with a thick wall 7-10 μm in diameter (consisting 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 when in contact with humans. Infection occurs by airborne, aerogenic, inhalation and transplacental pathway (rarely). Pneumocysts have a high tropism to the lung tissue, so even in fatal cases, the pathological process rarely goes beyond the lungs (this is associated with an extremely low virulence of the pathogen). Microorganisms attach to the pneumocytes, causing their desquamation. The main clinical signs of pneumocystosis are interstitial pneumonia and reactive alveolitis. Symptoms are nonspecific. The duration of the incubation period of pneumocystis pneumonia varies from 8-10 days to 5 weeks. The onset of the disease can not be distinguished from the banal infections of the respiratory tract. Clinical symptoms in AIDS patients develop more slowly than in patients with hemoblastosis. Dyspnea occurs very quickly (the frequency of respiratory movements is up to 30-50 per minute) and is accompanied by a dry or moist cough with scanty, viscous (sometimes foamy) sputum, cyanosis, fever. Pleural pain and hemoptysis are rare. At auscultation listen hard or weak breathing (locally or over the entire surface of the lungs), dry rales. As the progression of pneumonia, symptoms of respiratory and cardiovascular insufficiency may increase. The radiological picture at the beginning is nonspecific, then a radical decrease in the pneumatization of the lung tissue and an increase in the interstitial pattern are detected. More than half of the cases visualize bilateral cloud-like infiltrates (the "butterfly" symptom), and in the midst of the disease - abundant focal shadows ("cotton" lungs). At the beginning of the disease, a normal X-ray picture is found in a third of patients. Early involvement of the acini creates a picture of the so-called air bronchogram on radiographs (it is often mistakenly associated with interstitial lesions). However, further on the radiographs, the predominantly parenchymal nature of pneumonia is determined. In 10-30% of cases, asymmetric, as a rule, upper-annual infiltrates are noted. When CT is performed, peripheral infiltrates are detected (sometimes with foci of decay), reduced transparency ("frosted glass"), and emphysematous areas. Pneumothorax is the most common complication.

In the study of blood, hypochromic anemia, leukocytosis (up to 50x10 ⁹ / l) and eosinophilia are determined . When performing a biochemical blood test, an increase in LDH activity is observed up to 700-800 IU / L. The determination of PaO ₂ allows the identification of arterial hypoxemia. Detection of antibodies to P. Carinii is a nonspecific test; there are no culture methods. Therefore, the diagnosis is made on the basis of direct morphological imaging of pneumocysts in biological material using various methods (immunofluorescence, methods of staining Romanovsky-Giemsa and Grama samples, use of Schiff's reagents, etc.), and also carry out PCR diagnostics.

An open biopsy of the lung is performed with a progressive course of the disease. Macroscopically during the operation, the patient's lung looks enlarged, compacted, its consistency resembles rubber; note bullous and emphysematous changes, they reveal cavities of decay. Intraalveolar foamy exudate, diffuse alveolar lesions, epithelioid granulomas, desquamative interstitial pneumonitis, interstitial lymphoid infiltrates - histological changes in lung tissue in case of pneumocystis pneumonia. Survival of AIDS patients with pneumocystis pneumonia does not exceed 55%. The prognosis worsens significantly if the treatment is started against a background of acute respiratory failure, severe hypoxia, or with leukopenia. The lethality due to pneumonia and acute respiratory failure in AIDS patients is, according to different data, from 52.5 to 100%, and in the implementation of mechanical ventilation - 58-100%.

Cytomegalovirus infection

Cytomegalovirus infection, as a rule, proceeds latently. However, sometimes clinically expressed forms of the disease, caused by primary infection with cytomegalovirus, as well as reinfection or reactivation of the virus in the infected organism, are diagnosed. Generalized cytomegalovirus infection, accompanied by the emergence 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 of 10-20% of HIV-infected patients. The likelihood of occurrence and severity of the course of cytomegalovirus infection is associated with the degree of immunosuppression. If the amount of CD4 + lymphocytes in the blood is 100-200 cells per 1 μl, then the 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 in 1 μl, the probability of developing cytomegalovirus infection increases almost fourfold. With the total disappearance of CD4 + lymphocytes (less than 50 cells in 1 μl), the disease is registered in almost half of the infected patients.

If the content of CD4 + lymphocytes in the blood is large enough (more than 200 cells in 1 μl), then the manifestation of cytomegalovirus infection is rarely noted. This disease, as a rule, develops gradually, while detecting symptoms-precursors. Preceding the formation of pronounced organ disorders. In adults, a prolonged wave-like fever of the wrong type with a rise 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. With the defeat of the lungs, these symptoms are supplemented by a gradually increasing dry or sparse cough cough. At autopsy of deceased patients suffering from cytomegalovirus injury of respiratory organs, fibro-teleleuktas of the lungs with cysts and encapsulated abscesses are often found. The most severe symptom of cytomegalovirus infection is retinitis (diagnosed in 25-30% of patients). Patients complain of floating spots before their eyes, then there is a decrease in visual acuity. Loss of vision is irreversible, because this process develops as a result of inflammation and necrosis of the retina. With ophthalmoscopy, exudates and perivascular infiltrates are found on the retina. With cytomegalovirus esophagitis, the patient with swallowing has pain behind the sternum. In endoscopy, in a typical case, an extensive surface ulcer of the mucosa of the esophagus or stomach is visualized. Histological methods allow the detection of cytomegal cells in a biopsy specimen: the DNA of the virus can be determined using the PCR method. Cytomegalovirus infection can affect various organs of the digestive system, but more often colitis develops. The patient is concerned about abdominal pain, loose stool, weight loss and loss of appetite. Perforation of the intestine is the most formidable complication. As possible clinical symptoms of cytomegalovirus infection, ascending myelitis and polyneuropathy (subacute flow) also diagnose: encephalitis, characterized by dementia; cytomegalovirus hepatitis with simultaneous damage to the biliary tract and development of sclerosing cholangitis; adrenaline. Manifested by a sharp weakness and a decrease in arterial pressure. Sometimes there is epididymitis, cervicitis. Pancreatitis.

Specific lesion of vessels mainly microcirculatory bed and vessels of small caliber - a morphological feature of the pathological process with cytomegalovirus infection. To establish a clinical diagnosis of cytomegalovirus infection, it is necessary to conduct laboratory tests. Studies have shown that the presence of IgM antibodies (or high titers of IgG class antibodies) in the patient's blood, as well as the presence of virions in saliva, urine, semen and vaginal secretion is not enough either to establish the fact of active replication of the virus or to confirm the diagnosis of a manifest cytomegalovirus infection. Detection of the virus (its antigens or DNA) in the blood has a diagnostic value. A cytomegalovirus DNA titer is a reliable criterion for the high activity of cytomegalovirus, which proves its etiological role in the development of certain clinical symptoms. With an increase in the concentration of DNA virus in the plasma 10 times the probability of developing cytomegalovirus disease increases threefold. Determination of a high concentration of virus DNA in blood leukocytes and plasma requires the immediate initiation of etiotropic therapy.

[7], [8], [9], [10], [11], [12]

Toxoplasmosis

Toxoplasmosis is a disease caused by T. gondii, which most often occurs in HIV-infected patients against AIDS. Injection of toxoplasm into the human body leads to the formation of volumetric formations in the central nervous system (in 50-60% of cases) and the development of primary epileptic seizures (in 28% of cases). Toxoplasma - intracellular parasite; human infection occurs when eating foods (meat and vegetables) containing oocysts or tissue cysts. It is believed that the development of toxoplasmosis - the reactivation of a latent infection, since the presence of antibodies to toxoplasm in the serum of the blood, the probability of occurrence of toxoplasmosis increases tenfold. 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 in a few years or even decades after infection with HIV. In the form of cysts, toxoplasma persists up to 10-15 years. Mainly in the tissues of the brain and the organ of vision, as well as in internal organs. Pathomorphological changes in toxoplasmosis have a phase character. In the parasitemic phase, toxoplasm enters the regional lymph nodes, then penetrates the bloodstream and spreads to organs and tissues. In the second phase, there is fixation of toxoplasma in the visceral organs, leading to the development of necrotic and inflammatory changes and the formation of small granules. During the third (final) stage of toxoplasm, true cysts form in the tissues; The inflammatory reaction disappears, the foci of necrosis undergo calcification. Although toxoplasm can affect all organs and tissues, but, as a rule, in the HIV-infected patients, the cerebral form of the disease is recorded. They note a fever, headaches, appearance in 90% of cases of various focal neurological symptoms (hemiparesis, aphasia, mental and some other disorders). In the absence of adequate treatment, confusion, stunnedness, sopor and to whom as a result of cerebral edema are observed. When performing MRI or CT with contrast, they reveal multiple foci with ring-shaped amplification and perifocal edema, rarely - a single focus. Differential diagnosis is performed with lymphoma of the brain, tumors of another etiology, AIDS-dementia syndrome, multifocal leukoencephalopathy and tuberculomas. In almost every case, the primary lesion of certain organs and systems is diagnosed. Sometimes toxoplasmosis proceeds without formation of volumetric formations in the brain (such as herpetic encephalitis or meningoencephalitis). Extra-cerebral localization of toxoplasmosis (for example, interstitial pneumonia, myocarditis, chorioretinitis and digestive system damage) in AIDS patients is recorded in 1.5-2% of cases. The maximum number of foci of extra-cerebral localization is found in the study of the eye's visual apparatus (approximately 50% of cases). Dissemination (at least two localizations) occurs in 11.5% of cases. To diagnose toxoplasmosis is extremely difficult. Likvor with spinal puncture can be intact. The diagnosis is based on the clinical picture, MRI or CT, as well as the presence of antibodies to toxoplasma in the blood serum. A brain biopsy is performed if it is impossible to correctly establish a diagnosis. When biopsy in the affected areas, inflammation is observed with a necrosis zone located in the center.

Kaposi's Sarcoma

Kaposi's sarcoma is a multifocal vascular tumor that affects the skin, mucous membranes and internal organs. The development of Kaposi's sarcoma is associated with the human herpesvirus type 8, which was first detected in the skin of a patient with this tumor. Unlike endemic and classical variants of the disease, the epidemic form of sarcoma is recorded only in HIV-infected patients (mainly in homosexuals). In the pathogenesis of Kaposi's sarcoma, the leading role is assigned not to malignant degeneration of cells, but to the disruption of the production of cytokines controlling cell proliferation. Invasive growth for this tumor is not characteristic.

In a histological study, Kaposi's sarcoma shows an increased proliferation of spindle-shaped cells, similar to endothelial and smooth muscle cells of the vessels. Sarcoma in HIV-infected patients is not the same. Some patients are diagnosed with an easy form of the disease, others have a heavier form of the disease. The clinical signs of Kaposi's sarcoma are varied. Most often develop lesions of the skin, lymph nodes, the digestive system and the lungs. Tumor overgrowth can lead to lymphatic edema of surrounding tissues. In 80% of cases, the defeat of internal organs is combined with involvement in the pathological process of the skin. At the initial stages of the disease on the skin or mucous membrane, small rising red-lilac knots, often appearing at the site of injury, form. Around the nodular elements, sometimes there are small dark spots or a yellowish rim (resemble bruises). The diagnosis of Kaposi's sarcoma is based on histological data. At a biopsy of the amazed sites, proliferation of spindle-shaped cells, diapedesis of erythrocytes; they detect hemosiderin-containing macrophages, as well as inflammatory infiltrates. Shortness of breath is the first sign of lung damage in Kaposi's sarcoma. Sometimes hemoptysis is observed. On chest radiographs, bilateral darkening is defined in the lower lobes of the lungs, merging with the mediastinal boundaries and the contour of the diaphragm; often show an increase in the basal lymph nodes. Kaposi's sarcoma should be differentiated with lymphomas and mycobacterial infection that occurs with skin lesions. In 50% of patients, the digestive system is diagnosed, and in severe cases, intestinal obstruction or bleeding occurs. Involving the pathological process of the biliary tract leads to the development of mechanical jaundice.

Mortality and causes of death in HIV infection

The death of patients with HIV infection comes either from the progression of secondary diseases, or from any other concomitant diseases not associated with HIV. Generalized tuberculosis is the main cause of death of AIDS patients. In addition, the cause of death is considered pulmonary pathology (with the subsequent development of respiratory failure) and a manifest cytomegalovirus infection. Recently, the increase in mortality due to liver cirrhosis due to the development of viral hepatitis C on the background of chronic alcohol intoxication is recorded. Progression of chronic hepatitis in cirrhosis in these patients occurs within 2-3 years.