bubble_chart Overview

Acquired Immune Deficiency Syndrome, abbreviated as AIDS, is a newly recognized sexually transmitted disease identified in 1981. It is a fatal syndrome caused by the human immunodeficiency virus (HIV), leading to defects in the body's cellular immune function, resulting in a series of opportunistic infections and the development of tumors.

bubble_chart Epidemiology

The disease was first discovered in New York, USA, in 1978, with 7 cases in 1979, 12 cases in 1980, 204 cases in 1981, 750 cases in 1982, and a cumulative total of 1,739 cases by 1983, showing a steady annual increase. The World Health Organization announced that by the end of July 1992, statistics indicated the disease had spread to 164 countries, with approximately 500,000 people suffering from AIDS. The cumulative number of patients continued to rise over the years. By June 30, 1995, the World Health Organization reported that the number of registered Acquired Immune Deficiency Syndrome cases worldwide had reached nearly 1.17 million. The WHO believes the actual number is much higher, estimating that the total number of AIDS cases worldwide may have exceeded 5 million, with the total number of HIV-infected individuals surpassing 20 million, increasing by about 600 people daily. The death toll has reached nearly 1 million, earning it the title of the "disease of the century." Currently, the Americas have the highest number of cases, followed by Asia, with Europe ranking third. However, the number of HIV infections in Asia is rising rapidly. By the end of this century and the initial stage of the next, Asia will be in the diffusion phase of Acquired Immune Deficiency Syndrome. In Thailand and India, the virus has spread from high-risk groups to the general population, with 20% of adults already infected. The HIV-positive rate among pregnant women is as high as 8%. Within the next five years, most new infections will originate from Asia.

In mainland China, the first case was discovered in 1986 when an American-Argentinian fell ill in Xi'an and was diagnosed with AIDS after multiple examinations. This occurred four years after the first reported case worldwide. The same year, four HIV carriers were detected among hemophiliac patients in Zhejiang Province, marking the first discovery of HIV carriers in China. Subsequently, about 17 foreign HIV carriers were identified in China. By 1989, 146 HIV carriers were found in Yunnan, and three more were discovered in Beijing and Hebei.

Entering the 1990s, the HIV situation in China developed even more rapidly and unstoppably. According to figures released by the Ministry of Health, there were 492 HIV carriers and only 5 AIDS cases in 1990. The numbers rose annually, reaching 3,341 HIV carriers and 117 AIDS cases by 1995. Experts estimate that the actual number of HIV-infected individuals in China should be between 50,000 and 100,000. The growth rate over just five years is astonishing.

Many people still believe that Acquired Immune Deficiency Syndrome is more common in the United States, Europe, and Africa. However, with China's economic development and opening-up, AIDS has already spread across the country. Cases of HIV infection through imported Factor VIII injections have been reported, and major cities have successively reported AIDS cases. These developments demand heightened attention from the public.

Source of pestilence: AIDS patients and HIV carriers. The most infectious are those who are clinically asymptomatic but test positive for HIV antibodies, as they have the highest HIV isolation rate. Asymptomatic carriers are a major reason why the AIDS epidemic is difficult to control. Even more dangerous are those who are virus-positive but antibody-negative, a phenomenon more common in early-stage and advanced-stage patients.

Transmission routes: HIV is present in the blood, semen, vaginal secretions, saliva, tears, bone marrow fluid, urine, breast milk, and other bodily fluids of carriers, as well as in tissues such as the brain, skin, lymph nodes, and bone marrow. The primary sources of infection are blood, semen, vaginal secretions, and breast milk, with saliva being a rare but not negligible route.

Sexually transmitted infection: The essence of AIDS is a sexually transmitted disease, primarily contracted through sexual activity, especially among male homosexuals via "anal intercourse," which has the highest infection rate. The concentration of HIV in blood and semen is almost equal, making them the most potent sources of infection. Due to the vulnerability of the rectal mucosa to damage and bleeding during anal intercourse, HIV transmission is more common through this route. The more sexual partners one has, the younger the age at which sexual activity begins, and the presence of drug use further increase the likelihood of infection.

Sexual contact between men and women is most likely to lead to infection, with prostitution being the most severe, as prostitutes have a high chance of HIV infection, making pestilence highly probable. The HIV carrier rate among prostitutes in major U.S. cities is nearly 93%. In Africa, HIV transmission primarily occurs through heterosexual intercourse.

Blood and blood product pestilence: Transfusion of HIV-contaminated blood or blood products introduces the virus directly into the body, leading to infection, as well as puerperium infections and intravenous drug use through needle sharing. So far, no cases of AIDS infection through acupuncture have been reported. Among hemophiliac patients receiving Factor VIII transfusions, one-third have tested positive for HIV antibodies, and the numbers are now increasing exponentially. The primary reason is the lack of thorough HIV screening for blood donors. In Africa, the sharing of contaminated needles among drug users, where residual blood remains on the needle tips, directly injects the virus into the body, leading to widespread infection. This is especially common among women with sexually transmitted diseases. Organ transplants and artificial insemination are also significant transmission routes.

Vertical pestilence from mother to child: HIV-carrying mothers can transmit the virus to their infants through the placenta (intrauterine infection), during childbirth, or via breastfeeding.

Occupational risk factors: Medical personnel may come into contact with the virus through needle injuries or exposure to contaminated blood splashes on mucous membranes. There have been reports of healthcare workers developing the disease after being pricked by needles contaminated with HIV-infected blood. Although such cases are rare, they warrant serious attention.

bubble_chart Pathogen

Since the first case of Acquired Immune Deficiency Syndrome was discovered in 1981, scientists from various parts of the world have conducted arduous research on the disease. It was found that the HIV-1 virus is the pathogen of this disease, which has a significant inhibitory effect on the helper T-cell (CD4) immune system and is the main target of the virus. Additionally, macrophages and the mononuclear system are also cell populations with CD4 receptors and are target cells as well. Examining changes in the number of peripheral blood CD4 cell populations can help explore the progression of immune system abnormalities. Although extensive and persistent efforts have been made in the scientific foundational research of this disease, progress in prevention and treatment has been limited.

In the early 1980s, foreign scholars isolated lymphadenopathy-associated virus (LAV) and human T-lymphotropic virus type III (HTLV-III) from patients with Acquired Immune Deficiency Syndrome. At the time, HTLV-III/LAV was used to represent the Acquired Immune Deficiency Syndrome virus, but it has now been confirmed that the two are the same virus. In 1986, the International Committee on Taxonomy of Viruses decided to uniformly name it the human immunodeficiency virus (HIV).

HIV belongs to the Lentivirus genus of the Retroviridae family. It is a diploid-converting virus capable of transforming single-stranded viral RNA into double-stranded DNA, integrating it into the host cell's genome. This new hybrid is produced through the catalytic action of viral polymerase and reverse transcriptase. Members of this viral family also coexist in spherical forms, sharing a unified structure around the viral RNA and polymerase, as well as within the lipid membrane embedded with glycoproteins of a specific envelope.

HIV-1 structurally consists of two distinct units: the viral envelope and the viral core, surrounded by a host-derived lipid bilayer. Two major envelope glycoproteins, gp120 and gp41, are formed by enzymatic cleavage of a precursor protein, gp160, and together constitute a non-covalent peripheral protein complex. The gp41 protein is the transmembrane component, while gp120 protrudes from the viral surface and mediates viral attachment to host cells. The lipid bilayer is also embedded with host-derived proteins. The reassembled gp160 is synthesized in both mammalian and non-mammalian cell lines and is currently being tested for use in clinical vaccines for non-HIV-infected individuals, as well as to induce more effective immune responses in HIV-infected patients.

The viral core is composed of the nucleocapsid and viral enzymes. The former consists of four proteins: P7, P9, P17, and P24, all synthesized as a 53-kilodalton precursor protein, which is cleaved by HIV-1 protease.

Proteins P7 and P9 are tightly bound to viral RNA and form the nucleocapsid. Protein P24 is the primary protein in the inner shell surrounding the viral enzymes. Protein P17 adjoins the inner side of the lipid bilayer and stabilizes the viral particle components. The viral RNA within the nucleocapsid is critical for the viral enzymes: reverse transcriptase (RNA-dependent DNA polymerase), RNase H, integrase, and viral protease.

HIV is heat-sensitive and can be inactivated at 56°C for 30 minutes. It can also be inactivated by 50% ethanol or ether, 0.2% sodium hypochlorite, 0.1% household bleach, 0.3% hydrogen peroxide, or 0.5% Lysol after 5 minutes of treatment. However, it is not sensitive to ultraviolet light.

bubble_chart Pathogenesis

1. The Impact of HIV Infection on CD4 T Lymphocytes

The HIV virus is a retrovirus, meaning its genetic information exists in two identical single-stranded RNA templates. The virus can bind to human cells with CD4+ receptors, particularly CD4 T helper lymphocytes, and also interacts with galactocerebroside on the surface of neural cells. Reverse transcriptase converts the viral RNA into DNA, which then integrates into the human genome. The viral DNA sequence is carried for life by the infected cells and their progeny.

After entering the human body, HIV selectively targets lymphocytes with CD4 receptors, primarily CD4 T lymphocytes. When the viral envelope protein gp120 binds to the CD4 receptor on the surface of CD4 T lymphocytes, the viral membrane fuses with the cell membrane with the assistance of the transmembrane protein gp41, allowing the virus to enter the cell. Once inside, the virus rapidly sheds its outer shell, preparing for replication. Recent studies indicate that, in addition to the CD4 receptor, HIV entry into cells requires interaction between cell surface proteases and the V3 loop of gp120.

HIV replication in host cells begins with the reverse transcription of its two RNA strands into DNA by viral reverse transcriptase. This DNA serves as a template for further DNA replication by DNA polymerase. Some of this DNA remains in the cytoplasm, enabling low-level replication, while another portion integrates into the host cell's chromatin DNA, forming a provirus and entering a latent phase. After a latent infection period of 2–10 years, when the infected cell is activated, the proviral DNA is transcribed into RNA by transcriptase, and the RNA is then translated into proteins. These proteins are assembled into numerous new viral particles, which, upon release, continue to attack other CD4 T lymphocytes. The functional impairment and destruction of large numbers of CD4+ T lymphocytes by HIV are the primary causes of immune deficiency in AIDS patients.

Following HIV infection of CD4+ T lymphocytes, cellular dysfunction occurs. This manifests as defects in recognizing and responding to soluble antigens like tetanus toxin, despite normal responses to mitogens such as phytohemagglutinin (PHA). There is also reduced cytokine production, decreased IL-2R expression, and diminished ability to assist B lymphocytes. When HIV replicates extensively within host cells, it leads to cell lysis and rupture. During viral budding, HIV can cause membrane injury to the host cell. By inhibiting the synthesis of membrane phospholipids, HIV disrupts cell membrane function, resulting in cytopathic effects. Additionally, HIV can infect bone marrow stem cells, leading to a reduction in CD4+ T lymphocytes.

When the gp120 present on the surface of HIV-infected CD4+ T lymphocytes is expressed, it can bind to the CD4 molecules of uninfected CD4+ T lymphocytes, forming syncytia, thereby altering the permeability of the cell membrane and leading to cell lysis and destruction. Free gp120 can also bind to uninfected CD4+ T lymphocytes, acting as an antigen for antibody-dependent cellular cytotoxicity, making CD4+ T lymphocytes target cells that are attacked and injured by K cells. The transmembrane protein gp41 can inhibit the proliferative response of lymphocytes to mitogens and antigens, thereby reducing the number of CD4+ T lymphocytes. After HIV infection, there is usually an initial grade I to grade II reduction in CD4 T lymphocytes, with the total count remaining stable for several years, indicating that the virus is suppressed by the immune response. Over time, the CD4+ T cells progressively decline, indicating that the virus is gradually escaping immune control. Once the CD4+ T lymphocyte count drops to 0.2×10⁹/L (200 cells/μl) or lower, opportunistic infections may occur.

II. The Impact of HIV Infection on Other Immune Cells.

The impairment of immune function caused by HIV infection is not only due to the destruction of CD4+ T lymphocytes but also affects other immune cells to varying degrees.

(1) Monocytes and Macrophages: Because they also express CD4 receptors on their surface, they are susceptible to HIV infection, though the infection rate is much lower than that of CD4+ T lymphocytes. Studies have found that HIV-infected monocytes and macrophages play a role in disseminating HIV infection, as they can carry HIV into the central nervous system. In brain cells, the primary targets of HIV infection are monocytes and macrophages, such as microglial cells. HIV-infected monocytes and macrophages release toxic factors that can damage the nervous system. When a certain number of monocytes and macrophages become functionally impaired, the body's ability to resist HIV and other infections is reduced. Additionally, the impairment of CD4+ T lymphocyte function is also related to the functional damage of monocytes and macrophages.

(2) CD8+ T Lymphocytes: CD8+ T lymphocytes possess HIV-specific cytolytic activity. In the initial stage of HIV infection, they help suppress viral replication and spread. When CD8+ T lymphocyte function is impaired, the progression of HIV infection worsens. During the advanced stages of HIV infection, the number of HIV-1-specific cytotoxic T lymphocytes (CTLs) progressively decreases, suggesting that the loss of HIV-specific cytolytic activity in CD8+ T lymphocytes may be partly related to the reduction in CTLs. Selective mutations in HIV and the destruction of CD4+ T lymphocytes also contribute to the loss of HIV-specific cytolytic activity.

(3) B Lymphocytes: After HIV infection, B lymphocytes can be polyclonally activated, leading to an increase in their numbers in peripheral blood and the secretion of immunoglobulins, elevating IgG and IgM levels. However, B lymphocytes exhibit reduced responsiveness to new antigen stimulation. As a result, during the progression of HIV infection, pyogenic infections increase, while antibody responses to influenza A virus and hepatitis B vaccines decline. The mechanism behind the polyclonal activation of B lymphocytes in HIV infection remains unclear but may involve the lack of normal T-cell regulation, activation of B lymphocytes by Epstein-Barr virus, or direct activation by HIV.

III. Factors Promoting AIDS Development

After HIV infection, the virus maintains extremely low-level replication in the body for a considerable period, which explains the prolonged asymptomatic phase of AIDS. One reason is that cellular and humoral immunity can downregulate viral replication, and another is that some HIV becomes latent after entering CD4+ T lymphocytes. Many studies have shown that certain cytokines and other viral infections can activate HIV replication and expression. Reports suggest that glucocorticoids and interleukins (such as IL-4, IL-6, and IL-10) can synergistically enhance HIV replication. Tumor necrosis factor (TNF)-α, TNF-β, and IL-1 can also induce HIV expression, particularly TNF-α. Various gene products of other viruses can promote high-level HIV replication, and some viruses may even cooperate with HIV-1 to destroy CD4+ T lymphocytes. Clinically, AIDS patients often experience co-infections with cytomegalovirus, herpes viruses, Epstein-Barr virus, and human T-lymphotropic virus, which further accelerate disease progression.

IV. Immune Response After HIV Infection

The human immune system is the last line of defense against external infections. Many pathogens infect the body but are ultimately eliminated through cellular and humoral immunity. The immune system plays a certain inhibitory role in the initial stage of HIV infection. However, as the immune system is damaged and HIV mutates, the body's immune system eventually becomes powerless against HIV infection. HIV infection can stimulate the body to produce specific cellular immune responses and corresponding antibodies against various viral antigens. The body generates T lymphocyte-mediated cytotoxic effects, and T lymphocyte infiltration is observed in the brains of HIV-infected individuals. The suppression of HIV by CD8+ T lymphocytes and the lysis of HIV-infected target cells demonstrate that T cells play a role in inhibiting HIV replication. Antibodies produced by the body can neutralize free HIV viruses and HIV particles that have bound to cells but not yet entered them. Natural killer cells (NK cells) and killer cells (K cells) can kill and lyse HIV-infected cells through antibody-dependent cellular cytotoxicity. The body's cellular and humoral immune responses can control HIV replication and spread for a period of time. However, due to viral mutation and recombination, HIV can evade immune surveillance and cannot be completely eradicated by the immune system. When the immune system is further compromised, triggering factors may cause massive HIV replication and dissemination, ultimately leading to the onset of AIDS.

V. HIV Infection and Tumors

In HIV-infected individuals, the incidence of Kaposi's sarcoma, B-cell lymphoma, Hodgkin's disease, and certain other tumors is increased, which is directly related to the destruction of immune function, but may not be the sole cause. When B-cell lymphoma occurs in HIV-infected individuals, it is associated with EBV infection. HIV does not directly cause tumors, as viral sequences cannot be detected within the DNA of tumor cells.

The pathogenesis of HIV infection can be summarized as follows: ① After HIV enters the human body, it first binds to CD4+ T lymphocytes containing CD4 receptors on the cell surface, enters the cells for replication, and partially integrates into the chromosomal DNA of the cells, becoming latent; ② The cellular and humoral immune responses of the body resist HIV, resulting in low-level replication of the initially infected HIV; ③ Under the influence of other factors, the latent HIV is activated and undergoes extensive replication, widely invading CD4+ T lymphocytes, impairing the functions of CD4+ T lymphocytes, monocytes-macrophages, B lymphocytes, CD8+ T lymphocytes, and NK cells, ultimately leading to overall immune dysfunction and the eventual occurrence of a series of intractable opportunistic infections and tumors.

bubble_chart Clinical Manifestations

The clinical manifestations of HIV infection are divided into asymptomatic latency and severe opportunistic infections and tumor-related clinical symptoms.

I. Asymptomatic Latency Period

From 2 to 12 weeks after HIV infection (most commonly 6 to 8 weeks), anti-HIV antibodies become positive. At this time, a few individuals may exhibit transient acute infection symptoms, including fever, rash, stiffness, lymphadenopathy, arthralgia, myalgia, maculopapular rash, urticaria, abdominal pain, diarrhea, and, in rare cases, aseptic meningitis. Laboratory tests show normal white blood cell counts but increased monocytes, grade I reduction in lymphocyte ratio, and grade I thrombocytopenia. This is followed by a prolonged asymptomatic period, during which symptoms begin to appear as cellular immune function declines. The asymptomatic period can last 2 to 5 years or even over 15 years. Most adults and young people infected with HIV may remain symptom-free for a long time, but viral replication can still be detected. As the immune system is injured and the virus continues to multiply, most HIV-infected individuals develop related symptoms, such as persistent fatigue, prolonged fever, loss of appetite, and unexplained weight loss, followed by diarrhea, night sweats, and lymph node swelling (initially in the armpits, groin, etc.). When HIV invades the central nervous system, symptoms such as dementia and forgetfulness often appear. If only viral antibodies are present without the characteristic opportunistic infections of AIDS, it is termed AIDS-related complex (ARC) or persistent generalized lymphadenopathy (PGL).

About 10% of HIV-infected individuals eventually progress to AIDS within 2 to 5 years, while around 30% develop ARC, and approximately 60% remain asymptomatic carriers. About 15% of ARC cases progress to AIDS, meaning a large number of patients are asymptomatic carriers. This poses significant challenges for AIDS prevention.

Classification of HIV Infection and Diagnostic Criteria for AIDS.

The revised 1993 U.S. HIV infection classification system and diagnostic criteria for Acquired Immune Deficiency Syndrome cases in adolescents and adults are shown in Table 1.

Table 1: Revised 1993 U.S. HIV Infection Classification System and AIDS Diagnostic Criteria

This standard categorizes HIV-infected individuals into three clinical types (A, B, C) based on their clinical manifestations, with each type further divided into three levels according to CD4+ T-lymphocyte count. Among these three clinical classifications, except for all cases in category C being classified as Acquired Immune Deficiency Syndrome, any case with CD4+ T-lymphocytes <200/μl，或CD4+T 淋巴細胞百分比<14%的HIV感染者（即A3，B3），也可歸入艾滋病病例。

The U.S. CDC 1993 HIV Infection Classification System and Acquired Immune Deficiency Syndrome Diagnostic Criteria are explained in Table 2.

Table 2: Explanation of the U.S. CDC 1993 HIV Infection Classification System and Acquired Immune Deficiency Syndrome Diagnostic Criteria

Typical Acquired Immune Deficiency Syndrome has three basic characteristics: ① Severe cellular immune deficiency, especially CD4 T-lymphocyte deficiency; ② Occurrence of various fatal opportunistic infections, particularly Pneumocystis carinii pneumonia (PCP); ③ Development of various malignant tumors, especially Kaposi's sarcoma (KS). Among AIDS patients, 64% develop PCP, while KS has a higher incidence in homosexual and African AIDS cases. The mortality rate is highest in AIDS patients who simultaneously develop PCP and KS.

II. Common opportunistic infections in AIDS patients:

(1) Viral infections

1. Cytomegalovirus (CMV) infection is a rare disease but occurs in about 90% of AIDS patients. It is a common complication of AIDS and a significant cause of death. The infection can affect the lungs, digestive tract, liver, central nervous system, and multiple organs. About one-third of patients develop retinitis, with clinical symptoms such as fever, tachypnea, cyanosis, and dyspnea. Chest X-rays often show changes indicative of interstitial pneumonia, with diffuse ground-glass or reticular granular shadows in both lung fields. In advanced stages, alveolar changes develop due to the accumulation of secretions in the alveolar spaces. AIDS patients exhibit elevated antibody titers against CMV.

2. Herpes simplex virus (HSV) infection: Infections caused by HSV are related to CD4 T-lymphocyte counts. They manifest as refractory ulcerative lesions on the lips, genitals, and perianal areas, herpetic whitlow (extensive skin erosion), and other difficult-to-treat lesions with significant pain. Herpetic pneumonia, gastrointestinal involvement, and herpetic encephalitis may also occur. Serological diagnosis is of limited significance, and genetic diagnostic methods are preferred for confirmation. Treatment involves intravenous acyclovir.

3. Herpes zoster (shingles): This condition is caused by the varicella-zoster virus (VZV). In the U.S., herpes zoster in individuals under 50 should raise suspicion of HIV infection. In Africa, many patients present with facial herpes zoster, which can progress to retinal necrosis. Treatment is similar to that for herpes simplex.

(2) Bacterial infections

1. Atypical Acid-Fast Bacilli Infection: AIDS patients complicated with bacterial infections often present with systemic infections caused by mycobacteria. This disease has no subjective symptoms and lacks specific clinical manifestations. Some patients may experience digestive symptoms such as night sweats, high fever, general weakness, diarrhea, abdominal pain, and malabsorption. Additionally, anemia and weight loss may be observed. Diagnosis primarily relies on blood culture. Treatment commonly involves anti-subcutaneous node medications, but drug resistance is frequently encountered. Since this infection is not life-threatening, symptomatic treatments such as anti-inflammatory agents, antipyretics, analgesics, and nutritional support can be adopted.

2. Subcutaneous nodule disease: AIDS patients often experience recurrence of subcutaneous nodule disease. Extrapulmonary severe systemic infections are common, and chest X-rays are mostly normal. Due to the compromised immune system in AIDS patients, the tuberculin reaction for subcutaneous nodules is mostly negative. Since systemic infections are prevalent, the presence of subcutaneous nodule bacteria can be found in smears and cultures of feces, blood, urine, sputum, as well as biopsy specimens from lymph nodes, lungs, liver, gastrointestinal mucosa, and bone marrow, which holds significant diagnostic value. Treatment can involve anti-subcutaneous nodule medications. Since subcutaneous nodule bacteria can spread to healthy individuals through droplet infections, AIDS patients suspected of complicating subcutaneous nodule disease should take isoniazid for prevention.

(3) Deep fungal infections

1. Candidiasis: Candida infection is one of the most common opportunistic fungal infections. It is particularly prominent in AIDS patients, manifesting not only as superficial skin and oral candidiasis but also as esophageal candidiasis. Symptoms may include weight loss, fatigue, and nonspecific digestive symptoms such as dysphagia and retrosternal pain. Diagnosis can be confirmed by isolating Candida albicans. This condition holds an important position in the early diagnosis of AIDS. Treatment with antifungal agents can alleviate symptoms, but recurrence is common, indicating its refractory nature.

2. Cryptococcosis: The incidence of cryptococcosis in AIDS patients is 6%, with cryptococcal meningitis being the most common manifestation. It can also present as pulmonary cryptococcosis or cryptococcal pericarditis. Clinical symptoms primarily include fever, headache, fatigue, photophobia, altered mental status, and seizures. Cerebrospinal fluid examination is crucial for diagnosis, showing increased protein and cell counts, elevated intracranial pressure, and decreased glucose levels.

(4) Protozoan and Toxoplasma gondii infections

Pneumocystis carinii pneumonia (PCP): Pneumocystis carinii is a well-known typical opportunistic pathogen. It is often present in the alveoli of healthy individuals but usually remains latent. It is also a zoonotic disease. When the host's immune function declines for any reason, the pathogen can proliferate and exert its pathogenicity. In AIDS patients, due to immune system damage, Pneumocystis carinii pneumonia occurs.

Pneumocystis carinii pneumonia is a critically important opportunistic infection. At the initial onset of AIDS, 60% of patients develop this condition, and 80–85% will experience it during the entire course of the disease. Early-stage symptoms are characterized by progressive respiratory dysfunction due to hypoxemia, particularly presenting with panting, dyspnea, dry cough, and fever upon exertion.

Chest X-ray findings often show nonspecific infiltrative shadows, with 5% appearing normal. Sputum is viscous, and definitive diagnosis requires the detection of Pneumocystis carinii. Specimens are obtained by bronchoalveolar lavage, bronchial sampling, or open-lung biopsy.

There are clinical differences between PCP complicating AIDS and PCP in non-AIDS patients, as shown in Table 3.

Table 3 Differences Between AIDS Complicated by Pneumocystis carinii Pneumonia and Non-AIDS Complicated by Pneumocystis carinii Pneumonia

 Treatment: Compound formula sulfamethoxazole is the first-line drug, with an efficacy rate similar to that in other immunodeficient patients without AIDS, approximately 50～60%. However, the incidence of side effects such as drug-induced fever, rash, leukopenia, thrombocytopenia, and liver dysfunction is relatively high. Without treatment, the mortality rate is almost 100%.

AIDS patients may also develop complications similar to sporozoan infections, such as amoebiasis, toxoplasmosis, and cryptosporidiosis.

III. Acquired Immune Deficiency Syndrome Patients and Tumors

Due to immune dysfunction, tumor development in AIDS patients has become one of the primary causes of death. In 1986, an international symposium on "Kaposi's Sarcoma (KS)" and "AIDS" held in Nagasaki, Japan, confirmed that KS complicating AIDS differs from classical KS. Thus, the association between AIDS and tumors has drawn significant attention.

(1) Kaposi's Sarcoma (KS)

KS is a representative malignant tumor of AIDS. KS was first reported by Kaposi in 1872. Based on observations of three patients, he described the clinical characteristics of KS as idiopathic, multiple, pigmented fleshy tumors on the skin. It was considered an endemic disease in the equatorial regions of the African continent, primarily affecting middle-aged and elderly men under local geographical conditions, manifesting as numerous nodules of varying sizes on the limbs. Later generations referred to this disease as Kaposi's fleshy tumor.

1. Factors contributing to the formation of Kaposi's sarcoma (KS).

The exact factors leading to KS remain unclear. Regarding AIDS-associated KS, the causes, contributing factors, and their correlations are considered as follows:

(1) Approximately 30% of AIDS patients develop KS, and 90% of these AIDS-related epidemic KS cases are male homosexuals. From a geoviral pathological perspective, no direct correlation has been definitively established. Academically, during HIV infection, monocyte-derived angiogenic factors are observed, which some believe play a significant role in KS development. In 1995, scholars documented proliferative factors in KS cells. Long-term culture of KS cells in the supernatant of activated CD4-positive T cells demonstrated strong proliferative and pro-angiogenic activity on KS cells.

(2) Immunodeficiency state: The occurrence of KS in immunodeficiency is one of the key symptoms of AIDS. A close relationship exists between immunodeficiency and KS development. For instance, KS can occur during artificial immunosuppression in kidney transplant recipients or in leprosy patients. It may regress naturally after discontinuing immunosuppressive therapy. KS is more common in AIDS patients due to immunodeficiency.

(3) CMV: Cytomegalovirus (CMV) is detected in over 80% of AIDS-related KS cases. Whether this virus is linked to KS development remains unclear. Recently, a Japanese researcher detected CMV antibodies in KS patients' sera and identified CMV-related antigens in the nuclei and cytoplasm of atypical cells using fluorescent antibody techniques.

(4) EBV: The relationship between Epstein-Barr virus (EBV) and KS was indirectly studied in African-type lymphomas and KS, suggesting a geopathological link. The EBV-KS relationship is noted as a topic for future research.

2. Clinical symptoms of Kaposi's sarcoma.

KS can affect a wide range of areas, including the limbs, face, trunk, and skin. It may also occur in the oral mucosa, eyelids, and other mucosal surfaces. Additionally, organs such as the lungs, liver, and spleen, particularly the digestive tract, are at risk of severe hemorrhage. In summary, KS can manifest anywhere in the body, with the following clinical presentations:

① Nodular type: Cherry-red or purple, smooth-surfaced, raised lesions with clear borders and firm texture. Compression reduces their size, but they return to normal within 10 seconds (Hayne's sign). These nodules are distributed throughout the body but are most common on the lower limbs, feet, and forearms. Classic lesions bleed easily but are painless, typically affecting older patients, with a survival period of about 10 years.

② Infiltrative type: Lesions merge, forming ulcers or verrucous growths, often involving subcutaneous and bone tissues. This type mainly affects the lower limbs and feet, with nodules present in the lesions. It progresses rapidly, with a survival period of less than 3 years.

③ Generalized type: Involves widespread internal organ damage beyond skin lesions, such as the gastrointestinal tract, liver, spleen, respiratory tract, and lymph nodes. When lymph nodes are affected, it is termed lymphadenopathic KS. Although accounting for only 5% of cases, this type progresses quickly, has a poor prognosis, and can be life-threatening due to severe hemorrhage.

KS patients often suffer from malnutrition. Pediatric cases may exhibit rough skin, acrodermatitis enteropathica, scurvy-like lesions, and severe aphthae. Additionally, 50% of patients present with yellow nail syndrome.

3. Pathological changes in KS.

The tumor nodule is composed of spindle cells and small blood vessels, with the vessels being highly dilated and their walls thinned. There is cellular proliferation and infiltration of spindle endothelial cells, with the spindle cells showing good differentiation and being tightly arranged in a woven pattern, accompanied by abundant fibrous tissue between the cells. The small blood vessels consist of capillaries and sinusoids, and some fissures filled with red blood cells and bounded by spindle cells can be observed. The small blood vessels are scattered or patchily distributed among the spindle cells, with the two closely integrated. This lesion is located in the middle to lower layers of the dermis and may extend outward to invade the epidermis, forming an ulcer, or inward to invade the bone. Hemorrhage and hemosiderin deposition can sometimes be seen within the nodule. Surrounding the lesion, there may be dilation of small lymphatic vessels, lymphocyte infiltration, plasma cell reactions, and granulation tissue proliferation, presenting an irregular shape. Occasionally, changes such as lymphatic fleshy tumors, hemangiopericytomas, and multiple glomus tumors within tiny Kaposi's fleshy tumors may also be observed.

4. KS Treatment: The treatment of AIDS-related KS is more challenging than that of traditional KS.

(1) Combination Therapy

① Madagascar periwinkle herb alkaloid (Vinblastine) shows significant efficacy against AIDS-related KS. The initial dose is 4mg, administered via intravenous injection with 20-30ml of normal saline or 5% glucose. While maintaining white blood cell counts at 2.5-3×10⁹/L, the dose can gradually increase to 9mg per session, once weekly for 6-8 weeks.

② Vincristine is similar to the Madagascar periwinkle herb alkaloid and has certain therapeutic effects on AIDS-related KS. The dose is 1.4-2.0mg per session, administered via intravenous injection with 20-30ml of normal saline, once weekly.

③ Etoposide (vepesid, VP-16) is an effective drug for treating AIDS.

④ Bleomycin and doxorubicin.

(2) Radiotherapy can alleviate symptoms, with an effective dose of 1800-3000 rad.

(3) Local cryotherapy with liquid nitrogen.

(4) Immunomodulators: Interferon, isoprinosine, thymosin, interleukin, etc.

(II) Lymphoma

The occurrence of non-Hodgkin's lymphoma in HIV infection is an indicator for diagnosing AIDS. Approximately 5-10% of AIDS patients may develop non-Hodgkin's lymphoma, including primary central nervous system lymphoma. Most patients present with poorly differentiated lymphoma, including small cleaved cell and large cell immunoblastic types. These patients often exhibit extranodal lesions, frequently involving the bone marrow, central nervous system, gastrointestinal tract, liver, skin, and mucous membranes. Most patients show rapid lymph node enlargement, extranodal masses, or severe fever, night sweats, and weight loss. Some patients often present with primary central nervous system lymphoma.

bubble_chart Diagnosis

1. Diagnostic Basis:

(1) Epidemiological and Clinical Manifestations

(2) Laboratory Examinations

1. Primarily grade II or above cellular immune deficiencies including: CD4+ T lymphocyte depletion, decreased T lymphocyte function, significant reduction in peripheral blood lymphocytes, CD4<200/μl，CD4/CD8<1.0（正常人為1.25～2.1），遲發型變態反應皮試陰性，有絲分裂原刺激反應低下。
2. B lymphocyte dysfunction: polyclonal hypergammaglobulinemia, formation of circulating immune complexes, and autoantibody production.
3. Decreased NK cell activity.
4. Various pathogen examinations for the nature of disease infections, such as PCR. Histologically confirmed malignancies, such as KS.

(3) HIV Antibody Testing

1. Enzyme-linked immunosorbent assay (ELISA); 2. Particle agglutination test (PA); 3. Immunofluorescence assay (IFA); 4. Western blot (WB); 5. Radioimmunoprecipitation assay (RIP). The first three are commonly used for screening tests, while the latter two are used for confirmatory tests. Antibodies often cannot be detected within weeks or days after HIV infection, but 95% of infected individuals can test positive within 5 months. However, some may still test negative 3–4 years post-infection, necessitating direct HIV virus testing.

(4) PCR Testing for HIV Virus

2. Application of PCR Technology in HIV Testing

PCR can be used to track the natural history of HIV infection. It can detect viral sequences before other serological and virological markers appear, thus identifying the potential transmission risk of HIV in asymptomatic, seronegative patients. It is also useful for monitoring patients with long latency periods (4–7 years) and viral levels during antiviral therapy. Additionally, PCR can be used for HIV testing in infants born to HIV-1 seropositive mothers. During the first 6–9 months after birth, maternal antibodies are present in the infant's blood, so PCR can determine whether the infant is truly infected with HIV.

(1) Detection of HIV Sequences in Seropositive Sexually Transmitted Disease Patients

Some researchers prepared DNA from peripheral blood mononuclear cell cultures, semen cells, and semen supernatants of AIDS or ARC patients. They then used PCR and reverse transcriptase assays to detect HIV-1. PCR amplification products were annealed with 32P-labeled probes, digested with BstNI, and subjected to polyacrylamide gel electrophoresis and autoradiography. Results showed that 9 out of 28 reverse transcriptase-negative cell lines and 2 out of 9 indeterminate cell lines were positive. This indicates that many previously considered negative cell cultures were actually positive when tested with the more sensitive PCR method.

Proviral sequences can be detected in peripheral blood mononuclear cells from seropositive HIV-infected individuals. DNA prepared from the blood of seropositive homosexual men with virus isolated via coculture showed 100% detection of viral sequences by PCR. Among seronegative, coculture-negative homosexual samples, PCR amplification detected viral sequences in 64%, while seronegative normal samples tested negative by PCR, indicating no false positives. Due to the extensive heterogeneity of the HIV-1 genome, multiple primers (e.g., for LTR, gag, and env genes) can be used to improve detection rates. PCR detected HIV in 310 out of 313 confirmed antibody-positive samples (99%).

(2) Detection of HIV Sequences in Seronegative Sexually Transmitted Disease Patients

Due to the lag period between HIV infection and the appearance of an immune response, this serologically negative lag period [third stage] typically lasts from 6 weeks to 6 months, and the antibody-free period may be even longer. During this time, infected individuals often test negative for antibodies, meaning that seronegative individuals may still be infected with HIV. PCR testing can detect HIV-1 in high-risk populations 6 months earlier than seroconversion confirmation. For a small number of individuals with initially negative co-cultures, HIV-1 infection can even be diagnosed 24–39 months before seroconversion. For those with indeterminate serological test results, PCR can also be used for further analysis and confirmation.

(3) Detection of HIV Sequences in Newborns

Infants of HIV-infected mothers usually test positive by antibody detection due to the presence of maternal antibodies. However, in reality, only 20–60% of these infants are actually infected with HIV. Therefore, early diagnosis of HIV infection in these infants is crucial. It has been demonstrated that 30–50% of these newborns can contract HIV from their mothers in the uterus, during childbirth, through induced labor, or via postpartum breastfeeding. A seropositive result in newborns does not necessarily confirm HIV infection, as maternal HIV antibodies can persist for up to 15 months. Typically, infants do not exhibit any symptoms of HIV infection. Viral cell culture is not a reliable or practical method for infants; detecting HIV-specific IgM antibodies is also impossible in the presence of maternal antibodies; and identifying HIV antigens in serum is extremely difficult due to the excess of serum antibodies. Additionally, the progression of HIV infection in infants and young children is rapid. Early diagnosis is vital for timely intervention to delay or halt disease progression. Currently used antiviral treatments for dermatitis medicamentosa are highly toxic and thus unsuitable for HIV antibody-positive but uninfected infants. However, once HIV-DNA sequences are detected via PCR, antiviral therapy, along with immune-boosting and nutritional treatments, can be initiated. In one study, PCR testing of 14 newborns from seropositive mothers revealed 6 positive cases; among 10 children who were seronegative within 12–15 months after birth, 5 were PCR-positive. Peripheral blood mononuclear cells collected from one-month-old newborns of seropositive mothers showed that 7 PCR-positive infants developed AIDS within 10 months of testing, while 9 PCR-negative infants remained healthy during a 16-month follow-up. These findings highlight the importance of PCR technology for early and direct detection of HIV-1 in newborns of HIV-infected mothers and seronegative children.

PCR technology for detecting HIV-DNA sequences plays a critical role in confirming AIDS and ARC diagnoses. However, some argue that PCR testing is unnecessary for patients already known to be positive for HIV antibodies, antigens, or viral culture. The most suitable candidates for PCR testing are individuals suspected of HIV infection but lacking definitive serological evidence, such as infants born to HIV-positive mothers, sexual partners of positive patients, intravenous drug users, and individuals with suspicious serological reactions. PCR technology can also be used to screen blood products and vaccines for HIV.

III. Diagnostic Criteria for Acquired Immune Deficiency Syndrome:

1. Individuals who test positive for Acquired Immune Deficiency Syndrome virus antibodies and meet any one of the following criteria can be laboratory-confirmed as Acquired Immune Deficiency Syndrome patients.

1. A weight loss of more than 10% within the recent period (3–6 months), accompanied by persistent fever (≥38°C) for over one month;
2. A weight loss of more than 10% within the recent period (3–6 months), accompanied by persistent diarrhea (3–5 times daily) for over one month.
3. Pneumocystis carinii pneumonia (PCR).
4. Kaposi's sarcoma (KS).
5. Significant fungal or other opportunistic infections.

2. If antibody-positive individuals exhibit weight loss, fever, or diarrhea symptoms closely resembling those in criterion 1 above, they can be laboratory-confirmed as Acquired Immune Deficiency Syndrome patients.

1. CD4/CD8 (helper/suppressor) lymphocyte count ratio<1，CD4細胞計數下降；

2. Generalized lymphadenopathy;

3. Obvious symptoms and signs of central nervous system space-occupying sexually transmitted disease lesions, including dementia, loss of discernment, or motor dysfunction.

bubble_chart Treatment Measures

Currently, there are no specific therapeutic drugs for viral infectious diseases, so there is no effective treatment for AIDS. Additionally, the integration of HIV nucleic acid with host chromosomal DNA and its replication using host cells pose challenges for drug therapy. Early treatment of HIV infection is crucial. Treatment can slow the decline of immune function. HIV-infected individuals are at increased risk of subcutaneous nodules, bacterial pneumonia, and Pneumocystis carinii pneumonia, making early prevention essential.

1. Supportive therapy: Strive to improve the progressive wasting in AIDS patients as much as possible.

2. Immunomodulator therapy:

(1) Interleukin-2 (IL-2): Enhances the MHC-restricted cytotoxic activity of the body against HIV-infected cells and also boosts the activity of non-MHC-restricted natural killer cells (NK) and lymphokine-activated killer cells (LAK).

(2) Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF): Increase circulating neutrophils and enhance the body's anti-infection capability.

(3) Prodigiosin: Activates the pituitary-adrenal cortex system, regulates the internal environment and functions of the body, enhances adaptability to external environmental changes, stimulates the production of humoral antibodies, increases the total number of white blood cells, strengthens phagocytic function, and activates the body's defense system to resist the invasion of pathogenic microorganisms and viruses.

(4) Interferon (IFN): - α-interferon (IFN-α): Slightly increases CD4+ T cells in some patients, and 40% of Kaposi's sarcoma patients experience tumor regression. - β-interferon (IFN-β): Intravenous administration has effects similar to IFN-α, but subcutaneous injection shows weaker anti-Kaposi's sarcoma activity. - γ-interferon (IFN-γ): Enhances monocyte-macrophage activity and may have some effect against opportunistic infections such as toxoplasmosis.

3. Antiviral agents:

(1) Drugs that inhibit HIV binding and entry into host cells: Soluble rsCD4 can bind to HIV, occupying the CD4 binding site, preventing HIV gp120 from binding to CD4 on T lymphocytes and thus blocking infection of CD4 T lymphocytes.

Dose: In clinical trials, rsCD4 was administered at 30 mg/day via intramuscular or intravenous injection for 28 consecutive days.

(2) Drugs that inhibit HIV reverse transcriptase (RT): Block HIV replication by inhibiting reverse transcriptase. Effective drugs include zidovudine and dideoxycytidine.

bubble_chart Prognosis

The time from infection to the onset of symptoms continues to lengthen, which may be related to improved diagnostic techniques and earlier detection of patients. The reported asymptomatic survival period is becoming increasingly longer. Initially, it was estimated that the incubation period for adults was about 8 to 10 years, while children under 5 years old generally developed symptoms within two years. Historical studies on homosexual and heterosexual men have shown that about half of them did not develop AIDS within 10 years of initial HIV infection. Moreover, one study found that 8% of infected men remained normal for 10 to 15 years. A large-scale survey reported by the Royal Hospital in London indicated that asymptomatic survival could extend to 20 to 25 years. Recently, some have suggested that virtually all infected individuals will eventually develop AIDS symptoms. Therefore, when signs of infection appear, immediate treatment should be administered to prevent opportunistic infections. If opportunistic infections or tumors occur, corresponding treatments should be provided.

The survival time of AIDS patients is gradually increasing, though survey results vary by region. The length of survival is related to the level of healthcare, the time of infection, and the initial diagnosis of the disease. Most importantly, early diagnosis can prolong patient survival. Building confidence in overcoming the disease and maintaining an optimistic outlook on life also play a significant role in extending survival time.

bubble_chart Prevention

I. Specific Prevention

(1) With the 1993 CDC classification and diagnostic criteria in the United States, the scope of AIDS diagnosis has been expanded, facilitating the prevention and treatment of AIDS. Based on the reduction of CD4 T lymphocytes, certain medications are administered.

(2) Acquired Immune Deficiency Syndrome Vaccine: The United States conducted an intermediate-stage [second-stage] trial of two AIDS vaccines containing gp120 components on 296 participants. The trial was temporarily halted after six participants became infected. Thailand is currently conducting trials of a UBI synthetic vaccine.

(3) Prevention of Mother-to-Child Transmission: For pregnant women with Acquired Immune Deficiency Syndrome and CD4+ T lymphocyte counts >200/μl, the use of AIT (antiretroviral therapy) before delivery, during labor, and for infant treatment provides some protective effects.

II. Comprehensive Prevention

(1) Widespread dissemination of knowledge about Acquired Immune Deficiency Syndrome prevention, including transmission routes, clinical manifestations, and preventive measures.

(2) Strengthening moral education, prohibiting promiscuity—especially sexual relations with foreigners—and cracking down on underground prostitution.

(3) Avoiding sexual contact with HIV-infected individuals, AIDS patients, and high-risk populations.

(4) Prohibiting the sharing of syringes and needles with intravenous drug users.

(5) Mandatory HIV testing for imported blood, blood components, and blood products.

(6) Strict screening of domestic blood donors, with gradual implementation of HIV-negative testing before donation to prevent HIV transmission.

(7) HIV testing for blood, organ, tissue, and semen donors.

(8) Establishing Acquired Immune Deficiency Syndrome testing centers.

(9) Promoting the use of condoms and avoiding anal intercourse.

(10) Individuals with Acquired Immune Deficiency Syndrome or HIV infection should avoid pregnancy, and infants born to them should avoid breastfeeding. {|114|}

bubble_chart Differentiation

It needs to be differentiated from the following diseases:

1. Primary immunodeficiency diseases.

2. Secondary immunodeficiency diseases, caused by corticosteroids, chemotherapy, radiotherapy, or secondary immune diseases such as malignant tumors.

3. Idiopathic CD4+ T lymphocytopenia, which resembles AIDS but has no HIV infection.

4. Autoimmune diseases: connective tissue diseases, hematologic diseases, etc. AIDS with fever and weight loss needs to be differentiated from the above diseases.

5. Lymphadenopathy diseases: such as KS, Hodgkin's disease, lymphoma, and hematologic diseases.

6. Pseudo-Acquired Immune Deficiency Syndrome: AIDS phobia, a group of neurological symptoms similar to the early symptoms of Acquired Immune Deficiency Syndrome observed among homosexuals in the UK.

7. Central nervous system diseases: brain damage can be caused by Acquired Immune Deficiency Syndrome or other reasons and needs to be differentiated.