Author’s Note: The original purpose of this article is to summarize the knowledge about the natural course and clinical staging of HIV infection, which is popular knowledge for communication and learning. For friends who have high-risk behavior suspected of infection and after scientific consultation and testing to exclude HIV infection related symptoms, the symptoms described in this article should not be taken out of context and compared to avoid fear.
1.The natural course of HIV infection
(1) Acute infection period
This acute infection usually occurs about 1 to 2 weeks after exposure to HIV. During the acute infection period, HIV replicates heavily while CD4 cells drop dramatically. As a result, approximately 50-70% of infected individuals develop HIV viremia and clinical symptoms resulting from acute damage to the immune system. The main symptoms are systemic as well as cutaneous, neurological and intestinal symptoms, but they vary in severity.
Systemic symptoms include fever, sore throat, night sweats, arthralgia, enlarged lymph nodes, and hepatosplenomegaly. Skin injury is mainly manifested as a rash, mostly non-itchy red papules, occasionally diffuse urticaria or blistering rash, with the rash occurring mostly on the face and trunk, or in severe cases, all over the body.
The clinical manifestations are fever, headache, vomiting and meningeal irritation signs, and increased mononuclear cells and protein content in cerebrospinal fluid examination. Most of the above symptoms can recover on their own after 2 to 3 weeks. However, some patients have a prolonged course of the disease with recurrent meningitis symptoms. Individual patients may also present with peripheral neuropathy, myelopathy, and Green-Barre syndrome. Gastrointestinal symptoms: nausea, vomiting, diarrhea, oral ulcers, oral and esophageal candidiasis are common.
In general, the acute phase of HIV symptoms last about 2 to 4 weeks. However, the clinical symptoms of most infected individuals are generally mild and transient, like those of a cold or mononucleosis infection, and can return to normal after 2 to 3 weeks with symptomatic treatment or even without treatment. Therefore, many people in clinical practice are not sure of the true acute phase of infection. Frequency of common signs and symptoms (statistics vary from study to study): fever 96%, myalgia 54%, hepatosplenomegaly 14%, lymph node enlargement 74%, headache 32%, thrush 12%, pharyngitis 70%, diarrhea 32%, neurological symptoms 12%, rash 70%, nausea or vomiting 27%.
The acute infection period means that a certain amount of virus enters the lymphocytes, monocytes and peripheral lymph nodes in the body circulation, the virus replicates and multiplies rapidly, and the amount of virus increases dramatically, up to 100,000 to 1 million copies of HIV RNA per ml of plasma (105-106 copies/ml of plasma), so a fairly high level of HIV antigen can be found in the serum during the acute period. The clinical manifestations of discomfort and antibodies cannot be detected, then the immune system of the body quickly produces the corresponding antibodies, due to the defense function of the immune system, in just a few weeks, HIV RNA will drop to about 1,000 to 10,000 (103-104 copies/ml of plasma), the degree of reduction is closely related to the immune ability of the infected person, generally in 1 to 2 weeks after the appearance of symptoms can be measured Antibodies.
Based on this rule, any person suspected of being exposed to HIV with the above symptoms should be seen by the infectious disease department of the hospital and undergo the following tests: (1) viral load determination; (2) antigen determination; and (3) antibody determination. If necessary, T-lymphocyte subsets: including CD4 and CD8 lymphocyte tests should be done for reference. The presence of antigens in the serum during the acute phase is transient and is usually detected within only two weeks to one month. Therefore, after the symptoms should be promptly checked, some patients may not detect the antigen after this period; but the viral load after infection is impossible to detect, because there are not many domestic medical institutions with this test, and expensive, it is recommended that the conditions should be tested; at the same time, the antibody must be checked, so as to understand the body’s response, once the antibody appears, it has always existed and will not disappear. This is the fundamental basis for the diagnosis of HIV infection.
Since HIV mainly invades CD4 cells, some people will show a significant decrease in CD4 cells and an increase in CD8 cells at the beginning of the disease, so doctors should not only pay attention to the number of CD4 cells, but also to the ratio of CD4/CD8 cells. Sometimes the CD4 cell count can be in the normal range, but a significant increase in CD8 cells resulting in an inverted CD4/CD8 cell count also suggests HIV infection. With the emergence of antibodies, stabilization of the disease, and significant reduction in viral replication, the CD4 cell count can return to the normal range without treatment, and the ratio of CD4/CD8 cell count can also return to normal levels, with most acutely infected patients showing normal CD4 cell counts. The level of viral retention in the body during the acute infection period directly predicts the rate of progression to AIDS in HIV-infected patients.
(2) Asymptomatic phase
After acute HIV infection, the majority of patients have a long asymptomatic period, but each individual has a very different length. The asymptomatic period from HIV-1 infection to clinical symptoms or further development of AIDS is about 8-10 years for most patients. Long-term survivors of HIV-1 infection.
HIV is latent in the body for a long time in a persistent state of infection and evades clearance by the host immune system. The length of the clinical asymptomatic period is related to the number and type of infected viruses, the route of infection, individual differences in the immune status of the body, nutritional conditions and living habits. It is generally believed that this period is shorter for those infected by the blood route (months to 5 years, average 2 years) and longer for those infected by the sexual route (6 to 12 years, average 8 years).
During the asymptomatic period, HIV maintains a high replication equilibrium in the body, which means that the virus is produced in large numbers every day, but is also cleared in large numbers, constantly infecting and killing T lymphocytes, and also constantly mutating to escape the immune system. (2) The amount of virus in the blood basically remains at this low level, which is a relatively dynamic and stable equilibrium, but this is not an absolute static state, but a dynamic equilibrium in which HIV is constantly produced and constantly removed; this fast-paced and high-speed dynamic process has been confirmed many times in a large number of studies. (3) Rapid mutation of genetic genes (3.4×105/bp/replication cycle). In terms of pathogenesis, this phase is a slow CD4 cell deficiency phase, and this slow impairment of immune function puts the patient in latent danger of developing a fatal infection.
During the asymptomatic phase, some patients may develop persistent lymph node enlargement (PGL), which mainly presents as unexplained lymph node enlargement, clinically known as AIDS-related complex (ARC). These patients can maintain the disease for a considerable period of time and are limited to swollen lymph nodes. The diagnostic criteria for PGL are: (1) two or more enlarged lymph nodes in addition to the inguinal region; (2) lymph nodes ≥ 1 cm in diameter, without pressure or adhesions; (3) a duration of more than 3 months; and (4) no other etiology. Also these asymptomatic infected persons are the largest source of transmission of HIV-1 infection.
(3) AIDS stage
After a prolonged asymptomatic phase or presentation as ARC, patients may develop unexplained progressive wasting and weakness, followed by “opportunistic” infections, mostly in the form of Pneumocystis carinii pneumonia or central nervous system infections, which are the direct cause of death in most AIDS patients. The average survival of untreated patients entering this phase is 12 to 18 months. Kaposi’s sarcoma is a purple plaque that may appear on the skin of the entire body, but commonly on the extremities and in the oral mucosa. Kaposi’s sarcoma does not constitute a cause of death from HIV-1 infection, and the final direct cause of death in these patients remains infection. There are also a few HIV-1 infected patients who present with other malignancies such as lymphosarcoma and melanoma.
2. Three clinical types of HIV infection
(1) Typical progressives
In the early stage of infection, their immune function is not impaired, but their immune ability gradually declines within 8 to 10 years and finally develops into AIDS.
(2) Rapid Progressives
This group has a rapid decline in CD4 cell counts over 2 to 5 years, low levels of anti-HIV antibodies, and a poor ability of that antibody to neutralize HIV, or possibly augmented antibodies. The most striking feature in rapidly progressing individuals is the maintenance of a high viral load throughout HIV infection.
(3) Long-term survivors (also known as long-term nonprogressors)
These infected individuals maintain a healthy status for more than 12 years and maintain normal CD4 cell counts. These long-term survivors generally account for 8-10% of all infected patients, with a maximum of 17 years at present. These asymptomatic individuals can be found in hemophiliacs, intravenous drug users, heterosexual contacts, and newborns. Long-term survivors are often characterized by low viral load (plasma and PBMC), relatively nonpathogenic HIV strains, antibodies against existing HIV strains in individuals that do not exacerbate infection, type I cytokine production by PBMC, and a strong antiviral response by CD8 cells.
Factors associated with long-term survival include: (1) infection with a less replication-competent attenuated strain (nef deletion); (2) a strong CD8 cell antiviral response; (3) production of Th1-type cytokines (IL-2, IFN-γ, IL-12); (4) detectable neutralizing antibodies to one’s own strain; (5) a strong body; (6) deletion of an allele of CCR5 and expression of the CCR5 receptor on CD4 cells decreases, affecting the spread of NSI strains.
3.Clinical manifestations of AIDS
The incubation period of the disease is long, and it is generally believed that the disease can develop into AIDS in about 2-10 years, and HIV can be divided into four stages after invasion into human body.
(1) Stage I Acute infection
After primary HIV infection, a small number of patients may develop fever, general malaise, headache, anorexia, nausea, myalgia, arthralgia and swollen lymph nodes, similar to the symptoms of serum sickness. HIV and p24 antigen can be detected in the blood at this time. The CD4/CD8 ratio is inverted due to elevated CD8T cells, and thrombocytopenia may also occur. The symptoms usually last for 3 to 14 d and then disappear spontaneously.
(2) Stage II Asymptomatic infection
This stage may extend from the primary HIV infection or after the symptoms of acute infection have disappeared. There are no clinical symptoms, but antibodies to HIV as well as HIV core and envelope proteins are detectable in the serum and are infectious. This truncation can last for 2 to 10 years or longer.
(3) Stage III Persistent generalized lymph node enlargement syndrome (PGL)
The main manifestation is the enlargement of two or more lymph nodes in other parts of the body, except inguinal lymph nodes. It is characterized by enlarged lymph nodes with a diameter of 1 cm or more, tender texture, no pressure pain, and free movement without adhesions. Biopsy shows reactive hyperplasia of lymph nodes. Generally, the enlargement persists for more than 3 months. In some patients, the enlarged lymph nodes gradually dissipate after 1 year, but there are also patients who have enlarged again.
(4) Stage IV AIDS
Five types of manifestations may appear in this stage.
(1) Physical disease, i.e. fever, fatigue, malaise, night sweats, anorexia, weight loss, chronic diarrhea and easy to catch a cold. In addition to generalized lymph node enlargement, there may be hepatosplenomegaly. It becomes AIDS-related syndrome (ARS).
(ii) Neurological symptoms with headache, epilepsy, progressive dementia, and lower limb paralysis.
(iii) Severe clinical immunodeficiency with a variety of opportunistic pathogenic infections. These include Pneumocystis carinii, toxoplasma, Cryptosporidium, Cryptococcus, Candida, Mycobacterium tuberculosis, Mycobacterium avium, cytomegalovirus, herpesvirus, and EBV infection.
④ secondary tumors due to immunodeficiency, such as Karls Sarcoma, non-Hodgkin’s disease, etc.
⑤ Other diseases complicated by immunodeficiency, such as chronic lymphoid interstitial pneumonia, etc.