Sexually Transmitted Diseases - I. I. Mavrov 2005

Acquired Immunodeficiency Syndrome (AIDS)

Acquired Immunodeficiency Syndrome (AIDS) is an infectious disease characterized by immune system dysfunction and a spectrum of various clinical signs.

AIDS was first identified as a distinct disease in the USA in 1981. Initially, it was thought to affect primarily men from risk groups (homosexuals, drug users), but subsequent observations showed that women are equally susceptible to the condition. The number of infected individuals and AIDS cases is steadily growing, particularly in regions where other Sexually Transmitted Infections are prevalent and intravenous drug use is common.

Etiology. The disease is caused by the HUMAN IMMUNODEFICIENCY VIRUS (HIV), which belongs to the family Retroviridae, subfamily Lentivirus. HIV was first isolated from the Blood Leukocytes of a patient with lymphadenopathy in 1983. The virus is detected and cultured in human lymphocytes and monocytes. Currently, Two Types of virus are distinguished: HIV-1 and HIV-2, which differ in their structural and antigenic characteristics. A complete viral particle (virion) consists of a core containing double-stranded viral RNA, Reverse Transcriptase (revertase), integrase, and protease (Fig. 42). The core is surrounded by an envelope bearing a glycoprotein that mediates the attachment of HIV to CD4 receptors on human Cells. Upon entry into The Cell, under the action of reverse transcriptase, viral DNA is synthesized and integrates into the host cell DNA, which subsequently begins to produce Viral Particles. The HIV genome contains genes responsible for The production of envelope Proteins, revertase, and core structures, respectively. The HIV-2 genome differs from HIV-1 by the substitution of one Gene for another. Depending on The Structure of specific gene fragments, subtypes or clades are distinguished. Different subtypes may predominate in various HIV-affected populations. No clear correlation has been established between HIV subtype Classification and the clinical manifestations of the disease. However, it is well established that HIV Replication is strictly dependent on specific host cells.

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Fig. 42. STRUCTURE OF THE CAUSATIVE AGENT OF AIDS (HIV).

HIV is capable of actively invading cells On the surface of which the CD4 receptor is located, serving as the attachment site for the virus. These cells are mainly circulating elements of blood, lymph, and tissue fluid, as well as nonspecific elements of Nervous Tissue. HIV retains its viability for a prolonged period in cell-free Blood Plasma and semen. To date, the virus has also been detected in female genital secretions, saliva, lacrimal fluid, and breast milk. Active HIV replication is observed in lymphocytes and certain types of macrophages, indicating the essential involvement of these cells in The Development of the infectious process.

When HIV-infected lymphoid cells are dried at a Temperature of 30 °C, viral activity disappears after 3 days. When cell-free fluid with added human plasma is dried, the virus is inactivated at 23-27 °C within 7 days, and at 54-56 °C within 5 hours. In a liquid medium at 23-27 °C, HIV remains active for 15 days, and at 36-37 °C for 11 days. Recent studies have shown that under natural conditions, the virus in a dried state can persist for several hours or even days only in fluids containing a high concentration of HIV (blood, ejaculate). In blood intended for transfusion, HIV survives for years, and in frozen serum its activity persisted for about 10 years, according to observations by A. Srinivasan, D. York, McComick et al. (1986). In frozen semen, HIV persists for several months. Low concentrations of the virus in other fluids lead to its inactivation, thereby limiting the probability of HIV transmission.

Experimental infection in rabbits can be induced by intraperitoneal administration of virus-infected cells. AIDS develops in these animals within 8–10 months. Following the administration of blood plasma from AIDS patients to chimpanzees, the animals develop a condition resembling acquired immunodeficiency syndrome. These animals serve as the best experimental model for studying AIDS, including the testing of diagnostic and therapeutic agents.

Routes of transmission. The causative agent of AIDS in adults is transmitted primarily through sexual intercourse (vaginal or anal), transfusion of HIV-infected blood, intravenous administration of medications or drugs using non-sterile syringes upon reuse, and through Body Fluids of infected individuals (blood, semen, vaginal/cervical secretions). Anal and vaginal intercourse with an infected partner are the most frequently tracked routes of infection. Intrauterine transmission of the fetus from an infected mother is also possible.

To date, it is known that a vast number of people living on Earth and infected with HIV acquired the infection sexually. According to estimates by WHO experts and the Joint United Nations Programme on HIV/AIDS (UNAIDS), heterosexual contacts account for more than 90% of the 24.5 million HIV/AIDS cases in Africa.

In rare cases, when a woman is infected with HIV via a blood transfusion shortly after childbirth, transmission of the infection to the infant through breastfeeding is possible. Such observations are atypical, and the risk of transmitting the virus via breast milk is much lower compared to Other types of infection, including diarrheal diseases that may develop in newborns and infants if breastfeeding is withheld. Therefore, WHO strongly recommends the active promotion of breastfeeding among all women, including those infected with the AIDS virus.

HIV has been isolated from many body fluids, including saliva and tears, but no cases of transmission through any medium other than blood, semen, and vaginal-cervical secretions have been documented thus far. Intensive, so-called "wet" kisses (deep Tongue kissing) may pose a certain risk.

HIV transmission to healthcare workers may occur through occupational exposure to infected tissues or blood, e.g., during surgical Procedures (a case of AIDS in a female surgeon has been described), therapeutic interventions, examination of AIDS patients, autopsies, and the like.

Epidemiology and general pathology. Data from the UN AIDS Commission indicate that there are more than 50 million HIV-infected individuals worldwide, 16 million of whom have already died from AIDS. The number of second-generation AIDS patients—namely children, as well as women—increases annually.

As of April 1, 2002, about 45,000 HIV-infected individuals were registered in Ukraine, including nearly 2,000 children; 2,500 adults and 80 children have been diagnosed with AIDS. To date, over 1,250 adults and more than 50 children have died from this disease in our country. In terms of the epidemic's growth rate, Ukraine outpaces other Eastern European countries. More than 500 new infection cases are registered here every month, and AIDS is diagnosed in 50–60 patients. In reality, the situation is far more tragic: experts believe that only about one in ten actual virus carriers is detected.

The source of infection is an infected person or a virus carrier. The duration of the carrier state has not been established. There are reports that certain Donors whose semen was used for Artificial Insemination turned out to be carriers of the AIDS virus; consequently, this method of insemination is considered a potential source of infection.

The incubation period of AIDS ranges from a few months to 5 years, although the virus can remain inactive in The Human Body for even longer periods. It is estimated that the incubation period prior to manifest clinical disease has increased (according to recent data) from 4–5 to 8–10 years.

HIV transmission does not necessarily lead to the development of infection. In the majority of cases (60–70% of exposed individuals), the infection remains asymptomatic for an indefinite period, with no signs of disease for several years. In a subset of infected individuals (10–20%), acute manifestations of the disease are observed, while 23–26% exhibit an AIDS-like symptom complex. Recent epidemiological data indicate that not everyone is equally susceptible to the risk of contracting AIDS—only 50–60% of individuals who have been in contact with patients become infected. This may be associated with the presence of genetic susceptibility enabling HIV entry into host cells.

AIDS is most frequently diagnosed in individuals with promiscuous Sexual Behavior (homosexuals, heterosexuals, and bisexuals), as well as drug users who become infected through shared needles; less commonly, it affects hemophiliacs receiving untested blood products. Cases of the disease in infants and young children have been described. A link between children with AIDS and adult risk groups has been established, alongside similarities in their Clinical presentation and laboratory parameters.

According to recent data, less than 75% of HIV infections are attributable to sexual transmission, predominantly through heterosexual contact. The risk of transmission from a single instance of vaginal intercourse has not been precisely established, but it is thought to be low (1 in 500, or 0.2%) compared to the risk of transmitting other pathogens, such as Gonorrhea (about 30%). However, in some cases, a single heterosexual contact is quite sufficient for HIV transmission. There is compelling evidence that the presence of other sexually transmitted infections causing genital ulceration (Syphilis, Chancroid) increases the risk of HIV acquisition from a single sexual contact by 10-20 times.

In regions where HIV infection is rare or absent, the risk of sexual or otherwise acquired transmission is practically nonexistent. However, in most PARTS OF THE world, the prevalence of HIV infection is steadily increasing, and consequently, the risk of contact with an infected sexual partner is also growing. Therefore, selecting a sexual partner who does not belong to risk groups is of paramount importance for infection Prevention. Undoubtedly, the risk of infection escalates with an increasing number of sexual partners.

The degree of risk of HIV transmission is also related to the type of sexual contact. The highest risk is borne by the passive sexual partner in both heterosexual and homosexual intercourse. Consequently, women who play a passive role during intercourse may be at a greater risk of acquiring infection from an infected male partner than a man from an infected female partner.

Currently, a widespread dissemination of the infection is noted among intravenous drug users. The proportion of drug users among individuals suffering from AIDS increased from 13% in 1982 to 40% in 1987. According to American authors, the majority of women (61%) among AIDS patients suffer from substance dependence. Among male drug users with AIDS, 86% are African American or of Latin American descent.

Until recently, the primary route of HIV transmission in Ukraine was injection drug use. The proportion of injection drug users among all HIV-infected individuals was 83.4% in 1997, 76.6% in 1998, and 64.7% in 1999. Today, the HIV/AIDS epidemic has extended beyond high-risk groups. Sexual transmission increased from 11% in 1987 to 21% in 1999. The number of cases of mother-to-child HIV transmission from pregnant women is rising. In 1997, 0.09% of all pregnant women were infected with HIV, compared to 0.16% in 1999. An increasing number of HIV infections are being registered among individuals with multiple sexual partners (from 0.55% to 0.80%) and among patients with Sexually Transmitted Diseases (from 0.50% to 0.63%).

An analysis of epidemiological data characterizing the incidence of AIDS in the USA and France across various social groups indicates a marked increase in the number of HIV-infected individuals among those abusing prescription drug injections. In New York, for example, they accounted for 13% in 1986 and 50% in 1987. Thus, among HIV-positive women, 83% are injection victims (it was established that their sexual partners were not the source of infection). Practically all mothers of HIV-infected children also had a history of parenteral drug abuse.

Virological and epidemiological studies have made it possible to establish several general yet highly accurate epidemiological models of HIV infection across different regions. These models account for the estimated timeframe when HIV began to spread intensively within a given population, as well as the relative frequency of the three transmission routes: sexual, parenteral, and perinatal.

First model. Primary risk groups primarily include homosexual men and intravenous drug users (though a decline in incidence among homosexual men has been observed in recent years). A similar epidemiological model is currently observed in North America, Western Europe, Australia, and New Zealand.

Second model. The heterosexual route of transmission predominates. HIV infection and AIDS are diagnosed primarily among sexually active heterosexual individuals. Perinatal transmission is widespread. This model is characteristic of Sub-Saharan Africa and several Caribbean countries.

The third model is typical of Asian, Pacific, Eastern European, North African, and Middle Eastern countries. Here, HIV was detected in the mid-1980s. Although cases of HIV infection had been noted earlier, by the 1990s the prevalence of AIDS and HIV remained relatively low, and in most countries, no single transmission route was registered as dominant. However, over the past decade, the spread of HIV has accelerated primarily among sex workers and intravenous drug users.

Pathogenesis. HIV infection leads to the progressive destruction of the body's immune system. Host cell infection by HIV is determined by cellular properties and viral tropism. The primary target cell for HIV is the helper T-lymphocyte, which bears specific CD4 receptors on its membrane. In addition to T-4 lymphocytes, CD4 receptors are present on macrophages, monocytes, certain B-cell clones, epidermal Langerhans cells, follicular and other lymph node dendritic cells, as well as certain cells of The Nervous system.

Beginning with the earliest cycles of viral replication in the body, HIV infection leads to the progressive destruction of a specific population of T-lymphocytes—CD4⁺ lymphocytes—which play a key role in forming and maintaining the effector-level response of the infected individual's immune system. The fact that CD4⁺ lymphocytes serve as target cells for HIV is due to the structural Homology between their surface CD4 molecule and the envelope Glycoproteins of HIV. This enables the virus to recognize CD4⁺ lymphocytes, bind to them, and penetrate the cell interior, subsequently initiating the HIV replication cycle.

Active HIV replication is accompanied by progressive damage to The Immune System. Without effective suppression of viral replication via antiretroviral therapy, nearly all HIV-infected individuals experience a progressive decline in Immunity, increasing their susceptibility to opportunistic infections, oncological and neurological disorders, rare malignancies, and cachexia (Fig. 43).

According to preliminary estimates, clinical manifestations of AIDS develop annually in 28% of infected individuals. The disease progresses through six stages: the incubation period, acute infection, the latent period, persistent generalized lymphadenopathy, AIDS-related complex, and overt AIDS. However, this exact sequence of stages is not observed in all infected individuals.

On average, the incubation period lasts about 10 years. When infection occurs via blood transfusion, it is shortened to anywhere from 2 months to 4 years. In children, the average interval between infection and the onset of symptoms is twice as short as in adults.

The acute phase of HIV infection is typically preceded by the appearance of Antibodies to the virus in the blood (seroconversion). The body begins producing antibodies 6 to 12 weeks, and occasionally up to 8 months, after infection. However, it is now established that some individuals develop acute infection without antibody production as early as one week after HIV exposure. The acute stage is accompanied by fever, lymphadenopathy, night sweats, headache, and cough. Acute encephalopathy may also occur. During this period, only a single one of these symptoms may manifest.

Fig. 43. Cachexia in an AIDS patient.

During the latent period of HIV infection, symptoms are absent. However, the possibility of secondary coinfection must be kept in mind. Frequently, standard virological, immunological, and even histological diagnostic Methods prove insufficiently sensitive during this stage.

Persistent generalized lymphadenopathy is clinically manifested by enlarged Lymph Nodes (exceeding 1 cm in diameter). Typically, patients experience rapid enlargement of Lymph Nodes in 2–3 anatomical sites (excluding the genital area), with no preceding illness or medication use. This condition persists for at least 3 months. In one-third of HIV-infected individuals, this period, like the previous one, is asymptomatic.

The AIDS-related complex is characterized by clinical signs and immunological abnormalities similar to those seen in AIDS patients, but of lesser severity. Unlike AIDS patients, these individuals do not suffer from opportunistic infections, though weight loss may occur. Malaise, fatigue, lethargy, and loss of appetite are common. Abdominal discomfort may appear, and gastroenteritis or diarrhea is frequently diagnosed. Fever, night sweats, headaches, and Skin itching are observed in the majority of cases. Objective Examination reveals enlargement of the LYMPH NODES AND Spleen, along with tenderness upon Palpation. Additionally, patients quite often exhibit dermatitis, eczema, staphyloderma, fungal and viral infections, vascular changes, and papular rashes, which are frequently the initial signs of AIDS.

Overt AIDS represents the most severe form of HIV-related disease and is characterized by the presence of opportunistic infections and malignant tumors. This stage features the same clinical signs as the AIDS-related complex, but in a much more pronounced form.

The exact mechanism underlying the onset and manifestation of the disease remains fully undetermined, and it is still unclear why AIDS develops in some individuals with HIV antibodies while not in others. It is believed that a specific trigger mechanism for HIV disease progression exists, though it has not yet been identified. At the same time, it cannot be ruled out that comorbid conditions may play a role in the clinical behavior of HIV.

A particularly significant role in activating HIV is played by sexually transmitted infections (syphilis, herpesvirus infection, chlamydia, mycoplasmosis, etc.). These conditions are quite common in this patient demographic, fostered by casual sexual behaviors and multiple sexual partners. The co-occurrence of AIDS and syphilis is of major practical importance. The poor prognosis associated with the concurrence of HIV infection and a veneral disease is driven by pathogenesis (pathogens of sexually transmitted infections cause immune system dysfunction—"transitory" immunodeficiency—while AIDS is an infectious disease characterized predominantly by sustained cellular immune deficiency). HIV and sexually transmitted pathogens share several common traits: marked instability in the external environment leading to rapid inactivation; sexual transmission; prevalence within so-called risk groups; The ability to remain clinically latent for prolonged periods (months or years) upon entering the Organism; periodic disease flare-ups and severe clinical consequences; and early-stage Diagnosis via serological (immunological) methods.

Of the total number of identified HIV cases worldwide, more than one-third are women, predominantly of reproductive age (WHO, 1990). It remains unclear whether there are differences in the pathogenesis of HIV infection between men and women, and designing and conducting comparative studies in this direction is practically unfeasible. However, the assumption that no substantial differences exist appears quite compelling.

The prevalence of HIV among women varies widely across countries and social groups, ranging from high levels (1 in 4 women) to low levels (less than 1 in 20,000 women). In Germany, for instance, The ratio of infected women to men aged 20 to 29 is estimated at 1:2.8.

Initial reports on HIV infection indicated a potential acceleration of its clinical progression during Pregnancy. Common obstetric complications included fetal immaturity and low birth weight, Premature Rupture of membranes, and intrauterine death. Physicians recommend pregnancy termination for women with AIDS, as the vast majority of infants born to HIV-seropositive women show HIV antibodies in their blood.

According to WHO data, 15 to 45% of pregnant women can transmit HIV to their children before, during, or shortly after childbirth. Most of these women are unaware that they are infected. HIV does not impair reproductive function, and infected women may give birth to multiple children. There is still no definitive answer as to why the virus affects some newborns while leaving others uninfected. HIV crosses the Placenta During the first trimester of pregnancy and infects the fetus in 30–60% of cases.

HIV infection in a fetus or newborn leads to the development of an immunodeficiency that differs from both adult HIV and pediatric diseases of other origins. The mechanisms of disease progression in HIV-infected children are not yet fully understood. In a certain number of children infected before birth, symptoms appear within the first year of life, and only a few survive past the age of 2. Other children fall ill toward the end of this period or in early childhood, surviving up to 4–5 years. However, There are also cases where the first symptoms do not manifest until school age. Pediatric AIDS cases can be categorized into groups: (1) children of infected mothers or mothers who had sexual contact with men from high-risk AIDS groups; (2) children who underwent blood transfusions; and (3) children (20%) born to mothers who used drugs or had sexual relations with intravenous drug users.

Children with congenital HIV infection exhibit growth failure (75%), microcephaly (70%), and craniocerebral abnormalities (20%). Kaposi's Sarcoma and B-cell lymphomas are rare in children with AIDS. Unlike adult AIDS patients, children are characterized by a high frequency of bacterial diseases and acute infections of viral, fungal, protozoal, and mycobacterial etiologies.

Symptoms in infants during their first year of life typically appear around 5–6 months of age. As a rule, they suffer from chronic diarrhea, failure to thrive, various neurological disorders, lymphadenopathy, and hepatosplenomegaly. Such patients may experience Pneumonia, recurrent infections during the first 6 months of life, and very early-onset neurological complications.

Older children most commonly present with cutaneous and mucosal candidiasis, Pneumocystis pneumonia, and salmonella enteritis. Newborns and young children with AIDS frequently develop mumps, which is otherwise rare in these age groups—a detail that can be crucial for diagnosing congenital AIDS.

Many childhood illnesses (such as measles and diarrhea) follow a more severe course in HIV-infected patients. Therefore, the WHO recommends that all children born to HIV-positive mothers be vaccinated against diphtheria, tetanus, pertussis, poliomyelitis, measles, and tuberculosis, regardless of whether they have contracted the infection themselves. The BCG vaccine (against tuberculosis) should not be administered to children showing signs of progressive HIV infection due to the potential for severe adverse effects on a weakened immune system. However, even children with advanced infection must be vaccinated against other common childhood diseases that are normally preventable.

To reduce transmission rates before and during childbirth, women wishing to have a child, as well as their sexual partners, should be advised to voluntarily undergo HIV antibody testing. If either partner tests positive for the infection, they will need to carefully weigh the decision of whether to conceive, knowing in advance the risk of vertical transmission during pregnancy.

Research concerning mother-to-child transmission of HIV focuses on elucidating the biological mechanisms of HIV infection during pregnancy.

Based on modern epidemiological theory, as well as the localization of HIV within various biosubstrates of the infected human body (blood, semen, vaginal and cervical secretions, saliva, breast milk, tears, CEREBROSPINAL FLUID) and its routes of excretion, airborne-droplet and fecal-oral mechanisms of transmission can be ruled out. HIV infection is best classified as a bloodborne infection or an integumentary infection transmitted sexually. The most intriguing and paradoxical aspect of HIV epidemiology is that the possibilities of transmission are severely limited by the pathogen's restricted localization within the body and its low environmental stability. Despite this, HIV continues to spread rapidly among the global population.

Clinical Presentation

AIDS manifests through symptoms of previously rare diseases. These include Kaposi's sarcoma, lymphoreticular neoplasms, and other malignancies, as well as opportunistic Infections caused by pneumocysts, nocardiae, legionellae, Fungi, Mycoplasmas, chlamydiae, and other microorganisms. Tumors and infections may occur independently or in combination.

Upon HIV infection, the case fatality rate ranges from 38% to 65%. Mortality is 40% one year after disease onset, 80% after two years, and nearly 100% after three years.

Alongside genuine disease manifestations, certain individuals experience obsessive-compulsive states characterized by an overwhelming dread of AIDS, known as AIDS phobia. There are several levels of this pathological fear of AIDS. The first involves society at large, alarmed by epidemiological data—sometimes sensationalized by the press (in the U.S., for instance, Materials were published claiming that AIDS posed a greater threat to the public than nuclear weapons). The second comprises individuals from high-risk groups who have not contracted AIDS but have altered their lifestyles and sexual practices to engage in safer behavior. The third includes individuals from low-risk groups who are consumed by the fear of falling ill and constantly search themselves for signs of disease despite numerous negative laboratory results. It is this latter category of patients for whom the term "AIDS phobia" is most appropriate.

Psychopathy is less frequently observed in hypochondriacs, in whom the fear of contracting AIDS has transformed into the unshakable conviction that they are already infected. Fear of AIDS can trigger various mental disorders, obsessive states, Affective Disorders, Schizophrenia, and more.

One of the most characteristic signs of HIV infection is lymphadenopathy, most commonly involving the axillary, posterior and anterior cervical, and inguinal lymph nodes, and less frequently the supraclavicular and epitrochlear nodes. Lymphadenopathy is detected in 83% of patients. However, only half of these exhibit generalized persistent lymphadenopathy (enlargement of more than two non-inguinal lymph node groups persisting for over 3 months). Typically, the severity of lymphadenopathy varies significantly over time.

Early symptoms of AIDS include fever of unknown origin, generalized weakness, headaches, increased fatigue, weight loss, persistent diarrhea, cough, and hepatosplenomegaly. HIV-infected children often exhibit growth and developmental delays, frequently in the absence of other clinical signs for extended periods.

The most typical signs of AIDS are associated with opportunistic infections, malignant neoplasms, and neurological disorders. Approximately 80% of all AIDS patients present with one or two concurrently rare conditions: Pneumocystis pneumonia, a parasitic lung disease caused by Pneumocystis carinii; and Kaposi's sarcoma, a malignant vascular tumor that typically develops on specific areas of the skin or within the Oral Cavity and subsequently metastasizes to The Lymphatic system in the manner of malignant reticulosis (see insert XVI, 6). In AIDS patients, Kaposi's sarcoma frequently appears in atypical locations, including mucous membranes, progresses rapidly, and is observed in young individuals.

Other infections occurring in AIDS patients include extremely severe Yeast-like fungal infections (candidiasis of the Esophagus, Trachea, Bronchi, and Lungs; extrapulmonary cryptococcosis—meningoencephalitis, chronic diarrhea lasting over a month without other apparent causes); cytomegalovirus diseases (generalized cytomegalovirus infection affecting multiple Organ Systems, with the exception of lymph nodes and Liver); herpes infections with lesions extending beyond mucous membranes, accompanied by herpetic ulcers; and protozoan infections (such as cerebral Toxoplasmosis).

Severe complications of HIV infection include generalized mycobacteriosis, including typical tuberculosis, and interstitial lymphoid pneumonia in children under 13 years of age, both of which frequently result in death.

Populations with a high prevalence of AIDS more frequently exhibit undifferentiated forms of lymphoma, which differ from Hodgkin's lymphoma and primary Central Nervous System lymphoma (primary cerebral lymphoma), the latter detectable exclusively via computed tomography.

Central nervous system involvement—such as papovavirus-induced leukoencephalopathy—leads to serous encephalitis or meningoencephalitis accompanied by severe neurological symptoms. Indications of CNS involvement include apathy, fear, anxiety, irritability, restlessness, confusion, and loss of concentration.

The psychological profile of HIV-infected men exhibits certain specific features. Psychoneurotic states characterizing the acute phase are more common among heterosexual men (84.9%). Symptoms of organic CNS damage of varying severity are more frequently detected in homosexual men (78.2%). The predominance of organic symptomatology in this group is presumably linked both to the patient's behavioral patterns during the incubation period and to the presence of secondary sexually transmitted infections (in 37.4% of cases), notably syphilis (V.V. Belyaeva et al., 1990).

Depression and a sense of alienation are characteristic of many AIDS patients. They frequently experience anxiety driven by the fear of infecting individuals with whom they are in close contact.

In the later Stages of the disease, complications may include visual impairments caused by retinitis and retinal opacification; testicular atrophy and suppression of Spermatogenesis; and diffuse or focal alopecia.

Gastrointestinal disorders are significantly less common in adult patients than in children. They manifest as nausea, vomiting, diarrhea, and ulcerations across various Regions of the digestive tract. These ulcers can be accompanied by severe pain, intestinal bleeding, or perforation.

Renal function deterioration in AIDS patients may be linked to hypovolemia resulting from Water and Electrolyte loss through vomiting and diarrhea.

Cutaneous and mucosal lesions occupy a prominent place among the clinical manifestations of HIV infection (Fig. 44). Their nature is highly diverse. The most frequent include seborrheic dermatitis, candidiasis, viral skin infections, pyodermas, vascular alterations, and other integumentary and mucosal pathologies. Throughout the course of the disease, these lesions may regress, recur, succeed one another, present in various combinations, and eventually become widespread and severe (N.S. Potekaev, 1990).

Seborrheic dermatitis occurs in 50% of AIDS patients, presenting as large, clearly demarcated lesions. An unusual anatomical distribution—affecting the shoulders, buttocks, and thighs—is characteristic.

Candidiasis is a frequent clinical sign of HIV infection, distinguished by specific features: it affects young individuals, predominantly men; it frequently involves the mucous membranes of the oral cavity, genitals, and perianal region; and it tends to form large, painful foci prone to erosion and ulceration. Oral candidiasis frequently extends to the Pharynx and Esophagus. This accounts for difficulties in swallowing, retrosternal burning sensations, and pain during meals. Clinical manifestations of candidiasis frequently involve the vermilion border of the Lips, the corners of the Mouth, the perioral region, the inguinal folds, the torso, and the nail beds. Generalized dissemination of the process is also possible.

In addition to candidiasis, AIDS patients frequently present with rubrophytosis, tinea cruris, and pityriasis versicolor. Their common features include rapid generalization with The formation of large lesions that can localize on any part of the skin, including the scalp, face, hands, and feet. These mycotic infections follow a chronic course and respond poorly to Treatment.

Viral infections of the skin and mucous membranes are also common in HIV-infected individuals. Herpes simplex affects the oral cavity, genitalia, and perianal region. The condition is characterized by an Abundance of eruptive elements, occasionally leading to disease dissemination. Frequent relapses, along with a tendency toward erosion and ulceration, are consistently observed. Frequent recurrences of oral herpes lead to the formation of erosions that take a torpid course, fail to heal, and become increasingly painful during meals. The infection may spread to the oropharyngeal area, esophagus, and bronchi. Eruptions frequently involve the perioral zone, forming large lesions covered with thick crusts. Herpes lesions on the genitalia and in the perianal region are particularly prone to ulceration. The resulting ulcers do not exhibit a polycyclic outline; instead, they feature round, annular edges, show no tendency to heal, and cause severe pain. A highly painful herpetic proctitis may develop, clinically manifesting as mild edema and hyperemia of the rectal mucosa extending onto the perianal skin. Solitary vesicles are occasionally observed against this Background. Atypical localizations of herpes simplex manifestations, including primary lesions, are also possible, such as on the hands (especially the fingers) and legs, where chronic ulcers may develop.

Fig. 44. Skin and mucosal lesions of the face in an AIDS patient.

Herpes zoster can develop at various stages of HIV infection. It frequently serves as an early and solitary indicator of the disease (e.g., herpes zoster in the Trigeminal nerve distribution), occasionally manifesting even prior to seroconversion. Typically, a significant portion of the skin is involved, resulting in diffuse lesions; disseminated forms are also possible. The rashes often follow the path of Cranial Nerves and appear in the sacral region, are accompanied by severe pain, leave scars (frequently extensive ones), and recur—a phenomenon uncommon in immunocompetent individuals. Recurrences of herpesvirus infection indicate the progression of the disease to its final stage (N. S. Potekayev, 1990).

Cytomegalovirus skin and mucosal manifestations are rare. They present as petechial, purpuric, and vesiculobullous rashes. The localization, quantity, mutual arrangement, and dissemination of these elements are highly variable. Perianal cytomegalovirus lesions are typically associated with proctitis, colitis, and diarrhea.

Molluscum Contagiosum may also occur in the context of HIV infection. In adults, it is localized on the face and is characterized by rapid dissemination extending to the neck and scalp, an increase in the size of the elements, and their coalescence into massive growths. Relapses are virtually inevitable following the removal of these lesions.

Of particular note is a group of viral infections comprising proliferative disorders (oral hairy Leukoplakia, common warts, condylomata acuminata). The Emergence of hairy leukoplakia is linked to the Epstein-Barr virus and human papillomavirus. The lesion develops on the lateral surfaces of the tongue, usually unilaterally, and appears as a whitish-gray plaque that slightly rises above the surrounding tissue, featuring rounded outlines and indistinct borders; it sometimes extends to both lateral surfaces, other areas of the tongue, or even the buccal mucosa.

Common warts in HIV infection also tend to enlarge and spread, typically affecting the hands, feet, and face. Condylomata acuminata in HIV patients are localized on the external genitalia and in the perianal region, progressing rapidly. Their proliferation in number and size causes severe distress to patients. Relapses invariably occur following the removal of these warts.

Observations indicate that the most frequent clinical markers of HIV infection are vegetative, diffuse, and, notably, Chancriform Pyoderma. Vegetative pyoderma predominantly affects major skin folds and clinically mimics broad condylomas. Chancriform pyoderma, aside from its typical genital localization, develops on the upper lip and in the gluteal region. It appears as an erosive-ulcerative skin defect 1.0–1.5 cm in diameter with rounded contours and sharp borders. Palpation reveals a firm, elastic infiltrate at the Base of the erosion that extends well beyond its visible margins. Chancriform pyoderma may be accompanied by a false-positive Wassermann reaction. The diffuse variant of chancriform pyoderma is observed in infants and young children, manifesting as large infiltrated areas with bluish-pink skin covered with scales, serous and serosanguinous crusts, erosions, and phlyctenes. When localized on the face, it may be associated with angular cheilitis (perleche). Extensive lesions spanning large skin surfaces, such as the lower back, are frequently observed.

The potential emergence and progression of fistulas, abscesses, and other pyococcal skin lesions (folliculitis, acneform folliculitis, Various Forms of impetigo, etc.) against the background of HIV infection should also be considered.

Clinically detectable telangiectasias may be observed in HIV infection, frequently forming a large, crescent-shaped lesion extending from one shoulder to the other. These telangiectasias are located on and around the auricles, palms, fingers, and lower legs. They are frequently accompanied by erythematous macules, which, in such cases, typically localize in the oral cavity, on the hard palate, and on the inner surface of the lips. In addition to these vascular manifestations, leukoplastic vasculitis, generalized pseudothrombophlebitic syndrome, and livedo reticularis ("cutis marmorata") have been described.

Skin disorders in HIV infection are generally accompanied by lymphadenopathy. The process predominantly involves lymph nodes situated above the waist (sub- and supraclavicular, pre- and retroauricular, submandibular, and cervical nodes). Inguinal, femoral, and even popliteal lymph nodes may also become enlarged.

Skin alterations in HIV infection exhibit a persistent course and, when evaluated alongside other objective findings, provide a valid basis for a clinical suspicion of HIV infection.

Currently, for practical purposes, a clinical-morphological classification of AIDS forms is utilized: pulmonary, central nervous system-involved, gastrointestinal, and malignant neoplasms.

The pulmonary form manifests as dyspnea, Hypoxia, and chest pain. Radiological examination reveals diffuse pulmonary infiltrates. Pneumonia caused by Pneumocystis carinii is the most frequent fatal infection in these patients. Severe clinical presentations are also caused by pulmonary infections involving Legionella, cytomegalovirus, and other pathogens. Such pneumonias are characterized by an indolent course and a high rate of relapse following the cessation of therapy. They typically develop in young, previously healthy individuals.

The form characterized by central nervous system involvement is observed in approximately 30% of patients. It is caused by infections such as toxoplasmic cerebral abscess, Cryptococcal meningitis, progressive multifocal leukoencephalopathy, subacute cytomegalovirus encephalitis, and other infections, as well as neoplastic processes (e.g., primary central nervous system lymphoma), vascular complications (nonbacterial thrombotic endocarditis and cerebral hemorrhages associated with thrombocytopenia), and CNS involvement with focal neurological deficits and benign aseptic meningitis. Approximately one-third of AIDS patients suffer from dementia. It generally develops gradually, with patients exhibiting tremors and slowed movements that progress to severe dementia, loss of speech, urinary and fecal incontinence, and limb paralysis.

The gastrointestinal form is accompanied by diarrhea, nausea, vomiting, and weight loss, and is associated with infections caused by Cryptosporidium and other microorganisms. Diarrhea (intermittent or continuous) typically responds poorly to treatment administered over a 2–3 month period. In some cases, painful, bleeding gastric or intestinal ulcers develop. In a subset of patients, AIDS presents with a fever of unknown origin accompanied by stomatitis, esophageal lesions, nocturnal hyperhidrosis, malaise, asthenia, and weight loss of up to 10–15 kg unrelated to diet or steatorrhea. Some patients develop generalized mycotic processes.

Malignant neoplasms are detected in more than 30% of patients, notably Kaposi's sarcoma, which represents one of the clinical presentations of AIDS. The tumor originates from reticular elements of the perivascular Connective Tissue. The disease begins with the appearance of erythematous or hemorrhagic macules and nodular infiltrates of varying sizes. Nodular and plaque-like elements coalesce, and hematomas are frequently observed at ulceration sites. Typical localizations include the bony prominences of the lower extremities (ankles, toes, dorsum of the FOOT). The disease may manifest on any area of the skin, mucous membranes (most commonly the oral cavity), and external genitalia. Edema of the extremities (ranging up to elephantiasis) is quite common and may precede the appearance of core disease symptoms by several months or even years (Fig. 45). In some cases (averaging 10% of patients), Kaposi's sarcoma is accompanied by visceral involvement, most frequently affecting the lymph nodes, gastrointestinal tract, lungs, liver, Heart, and bones. Patients may develop a cough, dyspnea, hemoptysis, and arrhythmia. Atypical localizations of Kaposi's sarcoma include tumors in the soft palate, Larynx, trachea, esophagus, and eyes.

Other malignancies (lymphomas), including primary cerebral lymphoma, Burkitt's lymphoma, and immunoblastic sarcoma or lymphoma, are also observed in AIDS patients. Rare manifestations of AIDS include carcinomas, such as small-cell carcinoma of the rectum and oral cavity. Such patients generally develop Listeriosis pneumonia or Sepsis, as well as splenic abscesses.

Fig. 45. Kaposi's sarcoma in AIDS.

The clinical manifestations of AIDS in children mirror those in adults, although chronic diarrhea, anemia, and stomatitis predominate, exerting a detrimental impact on the child's GROWTH AND DEVELOPMENT.

Diagnosis

The diagnosis of AIDS is established by taking into account the epidemiological history, clinical symptoms, Assessment of the patient's immune status, detection of specific antibodies in the blood, and, in certain instances, Isolation of the HIV culture.

Laboratory Diagnostics. A diagnosis of AIDS cannot be established without laboratory confirmation of HIV infection. Specific diagnostics of HIV infection is based on the detection of specific Antigens, DNA and RNA fragments, viral activity (viral cultures), as well as the detection of antibodies (total and against specific antigens or viral antigen epitopes) of classes G and M.

HIV detection by cell culture. This technique was previously used to establish HIV-1 as the cause of AIDS. Mononuclear cells from HIV-infected patients were cultured in a nutrient medium along with lymphocytes from healthy donors, previously stimulated with PHA and supplemented with fetal bovine serum, L-glutamine, and interleukin-2. Positive cultures can be identified within 10 days. A negative result is determined in 1–1.5 months.

Quantitative cell culture methods. A method that measures the relative amount of virus in cells or serum. The culturing technique is the same as described above. To determine the viral load, $10\times 10^6$ ($10-20\times 6$) donor lymphocytes are cultured with serially diluted mononuclear cells ($10^6$; $10^5$; $10^4$; $10^3$; $10^2$; $10^1$) from HIV-infected individuals or with plasma dilutions obtained from patients. A positive culture with the smallest number of cells or the highest plasma dilution (detection of p24 or others) after 7 and 14 days of culturing characterizes The amount of virus present in the patient.

Detection of HIV antigens. Determination of p24 using solid-phase enzyme-linked immunosorbent assay (ELISA) with antibodies to this antigen coated on the solid phase.

Determination of proviral DNA and HIV genomic mRNA. It is possible to use Amplification methods for specific DNA sequences (in the case of RNA, reverse METABOLISM/31.html">Transcription is performed first). The sensitivity of this method is very high. With its help, target DNA fragments can be detected using a single cell. At the same time, high sensitivity is the cause of false-positive results due to contamination of material and Reagents.

Antibody detection. Antibodies to HIV-1 and HIV-2 can be detected using various methods (agglutination, immunoprecipitation, immunofluorescence, enzyme immunoassay, etc.) and test systems. A method for confirming HIV infection using a combination of three tests has been proposed.

Immunoblotting. Most frequently used to confirm HIV infection. In this assay, a complex of HIV proteins is fractionated by Polyacrylamide gel Electrophoresis. A nitrocellulose membrane is placed on the gel, and the separated HIV proteins are transferred to it by electroelution. The results are evaluated by detecting antibodies to individual HIV antigens in the analyzed sera (positive if at least one antigen of the env region is identified).

It should be noted that HIV-infected patients require dynamic follow-up. All laboratory and clinical data must be analyzed comprehensively and, if necessary, rechecked.

Establishing the diagnosis of HIV infection. The initial diagnosis is based on the results of Laboratory tests using confirmatory ELISA test systems that diagnose the presence of HIV antibodies, manufactured by ABBOT (coefficient of 6.5 and above), Genelavia mixt (coefficient of 10 and above), and Vironostika Uniform-2 (coefficient of 6 and above). If the test coefficients are below the specified levels, the laboratory performs additional analyses of the same serum sample using Serodia test systems (Table 22). In addition, re-examination of the patient's blood serum is recommended after 2 weeks to 1.5 months.

To clarify the diagnosis and conduct an initial medical examination upon receiving a positive result from a single screening test, the prospective HIV-infected individual is invited to the regional Center for the Prevention and Control of AIDS (AIDS Center). At the same time, a repeated blood draw is performed to rule out errors possible during initial screening (mandatory verification of the patient's identity based on identity documents). Blood is drawn strictly in accordance with the requirements of the Instruction of the Ministry of Health of Ukraine "On the Organization OF WORK in Laboratories for the Diagnostics of HIV Infection" (1994). The serum is sent directly to the laboratory of the regional AIDS Center with an individual referral form, and the "code" field must indicate "D" (dispensary registration).

Laboratory examination of individuals who have been in contact with HIV/AIDS patients. Individuals who have had sexual, parenteral, or medical contact with HIV/AIDS patients are placed under dispensary observation at their place of residence. Laboratory examination (specific testing) along with a clinical examination is performed at 3 and 6 months, and then annually. In the case of cohabitation (sexual contact), the contact person is subsequently examined once every 6 months.

Table 22 Scheme of using combinations of three different tests (excluding immunoblotting) in the diagnosis and confirmation of HIV infection (Van der Groen et al., 1991)

Organization of examinations for seropositive individuals. Specialized offices (departments) and AIDS control rooms (KIZ) keep records of individuals who tested positive for HIV by ELISA using two out of three test systems (ABBOT, Vironostika Uniform, Genelavia mixt). Patients are registered in a separate logbook and are subject to repeat laboratory examinations; blood collection (after 2 weeks, 1.5 months) is performed by a specialist of the office (department).

Organization of dispensary observation for children born to HIV-infected mothers (parents). Such children are subject to dispensary registration and observation for 18 months. Laboratory testing is performed after birth (cord blood is collected) and at 3, 6, 12, and 18 months (or upon clinical indication). To definitively establish the diagnosis in children, a comprehensive examination must be performed, including determination of total HIV antibodies, antibodies and p24 antigen, and immunoblot testing. After 18 months, following the analysis of (negative) test results, children are removed from the "D"-registry.

Repeat scheduled examinations. These are performed depending on the patient's clinical status and laboratory test results. In the absence of clinical manifestations (in the asymptomatic period) and a CD4 count above 500 cells/µL — once a year (Clinical and immunological studies). Scheduled examinations are performed more frequently in the presence of lymphadenopathy, prolonged fever, encephalopathy, or opportunistic infections. The frequency of tests is determined by the patient's clinical condition and immunological parameters. Hospitalization of individuals is based on clinical indications and the need to perform therapeutic and diagnostic procedures (bronchoscopy, etc.).

When establishing a diagnosis, assessing the immune status of patients is also important, although the immune abnormalities detected in AIDS are not pathognomonic exclusively for this disease.

Upon entering the body (into the bloodstream or through mucous membranes), HIV or HIV-infected cells enter the Circulation or Lymphatic vessels. The entry of HIV or HIV-infected cells into lymph nodes and other lymphoid tissues, where immune responses to antigens take place, promotes viral activation and leads to HIV replication and infection of T cells, macrophages, and dendritic cells.

Following the incubation period (typically 2 to 4 weeks), some patients show signs of primary HIV infection with the acute development of a mononucleosis-like syndrome, which includes fever, headache, lymphadenopathy, myalgia, rash, gastrointestinal disturbances, neurological symptoms, etc. This period is characterized by:

a) intense viremia with the detection of $10^3-10^4$ tissue culture infectious doses (TCID50) (50%) or an increase in genomic RNA copies to $10^5-10^6$ per mL of plasma. Isolation or detection of high infectious doses of HIV-1 from host Cells and Tissues reflects the rapid spread of the virus during the first few days. This also indicates that the antigenemia of the acute period reflects true viremia and that the patient is potentially highly contagious during the period of primary HIV-1 infection;

b) the number of lymphocytes in peripheral blood rapidly decreases; then, by 2–3 weeks, lymphocytosis may develop, mainly due to CD8⁺ lymphocytes with the possible appearance of atypical cells. Reverse Changes in the proportion of neutrophils are recorded, respectively, during the aforementioned time periods;

c) moderate thrombocytopenia is detected during the first 2 weeks, but it rarely has clinical significance;

d) acute-phase reactions are recorded (ESR may be elevated, C-reactive protein levels are increased in an average of 50% of patients). There are no characteristic changes in Hemoglobin levels;

e) the count of CD4⁺ T lymphocytes in peripheral blood sharply decreases, followed by recovery (in some cases incomplete) upon seroconversion; the CD4⁺/CD8⁺ mononuclear cell ratio undergoes similar changes;

f) in individuals in the asymptomatic period after primary infection, IgG antibodies are detected. Variations in the duration of the antibody detection period for identifying the latent form of the disease indicate The Need for sequential testing of the patient's serum from 3 to 6 months. Immunoblotting shows that antibodies to p24 or gp41 are detected first. Two weeks or slightly longer after the onset of symptomatic primary HIV-1 infection, immunoblot results were positive (H. Gaines et al., 1987). Antibodies to regulatory HIV viral proteins (from rev, tat, and other genes) are usually detected simultaneously, but in some cases even before the detection of antibodies to structural glycoproteins and proteins. The peak of IgM antibodies to HIV-1, which appear within 2 weeks of the illness preceding the IgG response, is observed between 2 and 5 weeks;

e) an increase in the functional activity of specific cytotoxic lymphocytes is recorded; a rapid decline in HIV replication during primary infection correlates with the emergence of a cytotoxic response (Znut et al., 1993);

f) several studies have noted a decreased in vitro lymphocyte response to mitogens and antigens during primary infection, along with a documented reduction in the functional activity of B lymphocytes;

g) in individuals with symptomatic primary HIV-1 infection, antibodies typically appear within a few weeks after the onset of clinical signs of primary infection, predominantly around the time symptoms subside or disappear. IgG antibodies are generally detected 2 to 6 weeks following disease onset. IgM antibodies to HIV-1 emerge within 2 weeks of infection and can be tested during the primary infection period. The initial IgM antibodies are typically directed against Gag or Env proteins. However, IgM antibodies are far from always detectable, and therefore a negative result cannot be considered definitive;

h) detecting p24 antigen in serum is crucial when the Differential diagnosis includes primary HIV-1 infection, as the p24 antigen can be detected here and in the cerebrospinal fluid prior to the detection of antibodies against Gag and Env proteins within the first few days (24 hours to 18 days) of the acute phase (H. A. Kessler et al., 1987; von Sydow et al., 1988). Therefore, p24 can serve as a laboratory marker during the primary infection period. However, the occurrence of false-positive reactions in p24 testing should also be noted.

The asymptomatic period is characterized by the following features:

a) viremia decreases. Titers characterized by 50% tissue culture infectious doses (TCID₅₀) and the number of quantified genomic RNA copies decline. Thus, the level of RNA copies in the blood of HIV-infected individuals during this period can range from undetectable (400-500 copies/mL) to high (30,000-100,000 copies/mL). The ISOLATION OF A high number of RNA copies or the determination of high infectious doses of HIV-1 from host cells and tissues reflects rapid progression of the viral infection. A subsequent "spontaneous" reduction in viral replication to minimal levels is possible (including following the resolution of opportunistic conditions that favored the activation of HIV replication during specific treatments), or it can be induced by specific courses of antiretroviral therapy;

b) upon seroconversion and the detection of p24 antibodies in blood serum, the p24 antigen is not detected;

c) clinical manifestations in some patients presenting with minimal symptoms, along with decreased lymphocyte and platelet counts in peripheral blood that generally lack independent clinical significance, can be attributed to this period;

d) the count of CD4⁺ T lymphocytes in peripheral blood recovers and typically fluctuates depending on time and other factors, including concurrent acute or underlying chronic illnesses, generally without dropping persistently (upon repeated tests after 1-2 weeks) below 400-500 cells/μL;

e) the reduced in vitro lymphocyte response to mitogens and antigens observed during primary infection may persist even after the completion of this period; a decrease in the functional activity of B lymphocytes has also been documented;

f) IgG antibodies are detected in patients following primary infection. Variations in the detection period of antibodies for diagnosing the latent form of the disease emphasize the necessity of sequential patient serum testing over a 3- to 6-month period. Immunoblotting shows that antibodies to p24 or the primary DR41 appear first. Two weeks or slightly more after the onset of symptomatic primary HIV-1 infection, immunoblotting results were positive (H. Gaines et al., 1987). Antibodies to regulatory HIV proteins (from rev, tat, and other genes) are usually detected simultaneously, but in some cases, prior to the detection of antibodies against structural glycoproteins and proteins. The peak of IgM antibodies to HIV-1, which appear within 2 weeks of disease onset preceding the IgG response, is observed between 2 and 5 weeks, with subsequent detection within 3 months.

Disease progression (pre-AIDS, AIDS). The progressive course of HIV infection is diagnosed based on a combination of laboratory and clinical criteria. Among laboratory changes, the following are noteworthy:

a) increase in viremia; the level of RNA copies in the blood of HIV-infected individuals during this period rises to 30,000-100,000 per 1 mL;

b) alteration of the HIV viral phenotype. While the early stage of the disease in patients during primary infection is characterized by relatively minor genome variations (especially in the env region), disease progression leads to the isolation of highly heterogeneous strains with more active replication in infected individuals. It should be noted that the tropism of the isolated strains also changes in the process (during the early period, it is predominantly macrophage-tropic, unable to infect resting T cells; subsequently, tropism toward T cells increases). As the disease progresses, syncytium-inducing human immunodeficiency Viruses are predominantly isolated from infected patients;

c) antibody titers to HIV proteins in blood serum gradually decrease, levels of antibodies to p24 decline, and the p24 antigen begins to be detected again (acidification of the serum releases the antigen from immune complexes, facilitating its detection);

d) the count of CD4⁺ T lymphocytes in peripheral blood is below 500/μL. When the CD4⁺ lymphocyte level drops below 200/μL, the onset of most opportunistic infections becomes possible; a decrease in mononuclear cell content to 50/μL is a very unfavorable prognostic indicator; a similar decline is observed regarding the percentage of CD4⁺ cells and the CD4⁺/CD8⁺ mononuclear cell ratio;

e) progressive reduction in the in vitro lymphocyte response to mitogens and antigens observed during primary infection; cutaneous anergy develops, and the functional activity of B lymphocytes declines;

f) anemia; decreased hematocrit and albumin levels; elevated ESR (ERYTHROCYTE SEDIMENTATION RATE);

g) increasing levels of acid-labile interferon, neopterin (3-5 ng/mL in asymptomatic infection), and β₂-microglobulin (less than 3 ng/mL).

Treatment

The management of AIDS patients involves The Use of antiviral drugs that suppress viral reproduction. After confirming the diagnosis, strategies for ongoing patient care are determined. To assess the risk of HIV progression and to determine the optimal timing for initiating or modifying antiretroviral therapy, plasma RNA levels are measured to evaluate HIV replication activity and the associated rate of CD4⁺ lymphocyte destruction (the CD4⁺ lymphocyte count indicates the degree of immune system impairment).

In cases of newly diagnosed HIV infection, It is important to know the baseline HIV RNA level prior to clinical deterioration. During the first 6 months following infection, the HIV RNA level does not allow for an accurate prognosis of disease progression risk. Over the subsequent 3 months, it stabilizes, and this value can then be used to assess the risk of disease progression. HIV RNA may remain virtually unchanged for many months and even years.

The therapeutic approach should be individualized, based on the risk level determined by HIV RNA levels and CD4⁺ lymphocyte counts. The decision of when to initiate antiretroviral therapy should be made depending on the risk of HIV progression and the severity of immunodeficiency. If antiretroviral therapy is started before immunological and virological signs of disease progression appear, its positive effect may be most pronounced and sustained.

Antiviral Therapy is prescribed to patients starting from the acute infection stage. The most crucial test at the initial stage of treatment is counting the number of CD4⁺ T lymphocytes in the peripheral blood of HIV-infected individuals. Antiviral therapy is indicated when the CD4⁺ T lymphocyte count is below 500/μL of blood. When the CD4⁺ T lymphocyte level is below 200/μL, treatment is administered continuously; when the CD4⁺ T lymphocyte level is below 500 but above 200 cells/μL, it is given in 3-month courses separated by 3-month intervals. If the CD4⁺ level is unknown during the primary manifestation stage, maintenance therapy is not prescribed; during the AIDS-related complex (ARC) stage, it is recommended in courses, and during the full-blown AIDS stage, it is administered continuously.

For sustained and profound suppression of HIV replication, a combination of two nucleoside reverse transcriptase inhibitors with a potent protease inhibitor is effective. In treatment-naive patients, suppression of HIV replication to undetectable levels has been observed when administering two nucleoside reverse transcriptase inhibitors combined with a non-nucleoside reverse transcriptase inhibitor, such as zidovudine, didanosine, or nevirapine. A combination of two antiretroviral drugs, rather than three, may also be used.

The best way to prevent the emergence of HIV-resistant strains is the combination therapy of highly active antiretroviral drugs, which ensures sustained maximum suppression of viral replication. During combination therapy, it is essential to follow the recommended doses and administration schedules for each antiretroviral agent (Table 23). Monotherapy is currently not prescribed. However, I. Bryson (1996) recommends treating HIV-infected pregnant women with zidovudine, which reduces The rate of mother-to-child transmission down to 8% (by comparison, this figure is 24% among untreated patients).

Pathogenetic and symptomatic treatments are administered According to the clinical manifestations. A critical practical objective is the correction of systemic pathogenetic disorders (Functions of the respiratory, cardiovascular, and nervous systems, electrolyte balance, etc.), alongside immune system stimulation. Transfusion of the patient's own blood irradiated with ultraviolet rays, combined with other therapeutic modalities, is also advisable.

The core principle of AIDS management, as with other viral diseases, is the timely Treatment of the underlying condition and its complications—most notably pneumocystis pneumonia, Kaposi's sarcoma, and central nervous system lymphoma.

It is generally considered that treating opportunistic infections and Kaposi's sarcoma in AIDS patients requires administering sufficiently high doses of Antibiotics AND CHEMOTHERAPEUTIC agents, preferably in combination. When selecting a therapeutic agent, clinicians must consider not only pathogen susceptibility but also patient tolerance and renal function, due to the risk of drug accumulation in the body. Treatment outcomes also depend on strict adherence to the therapeutic regimen and adequate treatment duration.

Table 23 Specific Anti-HIV Therapeutics

Currently, prolonged therapy lasting over 6 weeks is used to treat opportunistic infections and Kaposi's sarcoma. The treatment protocol depends on the disease phase and activity.

There are numerous guidelines and regimens specifying drug dosages and administration routes, and practically every specialist follows their own protocol. Standard treatment typically begins with high doses of an antibiotic or other chemotherapeutic agent, combining them when necessary. Subsequently, patients are maintained on baseline doses until the disease activity subsides and eventually ceases altogether.

Drawing on accumulated global clinical experience, certain recommendations can be provided for selecting therapeutic agents to treat opportunistic infections and Kaposi's sarcoma in AIDS patients. For pneumocystis pneumonia, pentamidine, Biseptol, sulfamethoxazole, and pyrimethamine are employed. For toxoplasmosis, spiramycin, sulfatidine, pyrimethamine, Biseptol, and clindamycin are indicated. Infections caused by Mycobacterium avium are difficult to treat due to the lack of specific agents; in such cases, antituberculosis drugs are prescribed: ethambutol, streptomycin, ethionamide, cycloserine, ansamycin, clofazimine, and amikacin. Mycoses are treated with amphotericin B combined with 5-fluorocytosine, nystatin, or Nizoral. For herpes infections, acyclovir and other antiviral agents are utilized.

To treat Kaposi's sarcoma in AIDS patients, the Alkaloids vincristine and vinblastine are recommended, alongside cytostatics such as sarcolysin, bruneomycin, phosphazine, fotrin, tomyzin, rongeron, and prospidin.

Despite the wide array of drugs and treatment regimens available for AIDS patients, current therapeutic outcomes remain modest and do not lead to a complete cure, as clinical remissions are characterized merely by the suppression of viral replication and, in some cases, a significant reduction in morphological disease markers rather than their complete eradication. Therefore, halting viral replication remains the primary pathway likely to restore the body's resistance to opportunistic infections and malignancies through the immune system's recovery or the replacement of destroyed immune cells.

A frequent complication in treating AIDS patients is "chemical overload" caused by medications administered in the final stages of the disease against viruses, fungi, unicellular parasites, and other microorganisms. Consequently, many patients succumb not to secondary infections, but to the Toxic effects of high drug doses.

Adequate therapy involves fostering a supportive psychological environment for the patient, timely Diagnosis and treatment of primary, background, and opportunistic diseases, and rigorous follow-up monitoring.

Prevention

Emergency prophylaxis is advisable following suspected or confirmed exposure to HIV. Antiretroviral therapy significantly reduces the likelihood of HIV transmission after unprotected sexual contact. Prophylactic treatment also prevents occupational HIV infection in healthcare workers who suffer accidental injuries from instruments contaminated with infectious blood.

Specific HIV prevention must also include vaccination. The Institute of Human Virology (Baltimore, USA) has developed an oral vaccine for HIV/AIDS prevention. Animal experiments confirm the vaccine's high immunogenicity (high titers of induced antibodies) and low reactogenicity (minimal adverse reactions). Clinical trials are currently underway.

Undoubtedly, programs aimed at preventing new HIV infections must form the cornerstone of the fight against AIDS in the coming decades. Various approaches within a comprehensive AIDS prevention strategy are currently being studied and discussed. Emphasis is placed on disease prevention through public awareness campaigns promoting safer sex practices, lifestyle modifications, risk-reduction strategies among high-risk groups, and the analysis of social conditions contributing to the spread of the disease. Both legal and medical aspects of reducing morbidity and curbing HIV transmission are actively considered.

Ethical considerations play a crucial role in combating AIDS, particularly regarding behavioral patterns in specific social groups (taking epidemiological consequences into account). Legal regulation of sexual behavior is necessary and well-founded.

Preventive outreach among homosexual individuals is of paramount importance, as they often engage in numerous sexual encounters with indiscriminate partner Selection and suffer high rates of sexually transmitted infections, including AIDS. Preventive efforts are further complicated by the fact that the erotic preferences of gay men and lesbians diverge from societal norms, generating a range of challenges for both the individuals themselves and society at large. Meanwhile, these populations comprise 35% (and potentially more) of the population. Shared sexual orientation and societal hostility drive them to seek out peers, fostering a distinct subculture. This factor must be taken into account when designing AIDS prevention initiatives.

Another key front in the fight against AIDS is the battle against drug addiction. The primary driver of HIV spread among intravenous drug users is the sharing of needles and syringes, compounded by the existence of clandestine drug dens offering rental equipment for intravenous drug administration.

Given the current lack of reliable methods to eliminate HIV from blood and blood products, screening for HIV-negative donors is of paramount importance. Systematic immunological and virological testing of donors for HIV is essential. Particular difficulties arise in preventing infection among recipients of blood products, as these are manufactured from large pools of mixed donor blood.

HIV infection does not always manifest clinically, even when antibodies against the pathogen are present in the body. Consequently, standard precautions recommended for healthcare personnel are necessary. When handling blood, tissues, semen, and similar biological materials, medical staff must exercise professional caution, as is mandatory for blood-borne and body-fluid-borne viral infections. Contact with blood, semen, urine, cervical and urethral secretions, saliva, other tissue fluids, and mucous membranes should be minimized. Instrumental examinations should be performed only when clinically indicated.

Of primary importance is strict adherence to medical instrument sterilization protocols and the widespread clinical adoption of single-use needles, syringes, and transfusion sets.

HIV is rapidly inactivated in the external environment, making the probability of transmission via casual daily contacts—such as handshakes, shared meals, coughing, or sneezing—extremely low. Nevertheless, such a possibility should not be entirely dismissed. Therefore, standard self-protection measures akin to those used for other infectious diseases should be observed, including washing dishware with hot soapy water rather than merely rinsing it under the tap, and thoroughly washing hands after contact with any bodily fluids of an infected person, especially blood.

Today, developing treatments for AIDS is just as vital as formulating sanitary education campaigns for all segments of the population, grounded in comprehensive and transparent information.