From the above results, we can find that some research results of ILWH are similar to those of general HIV-infected people, including aging [4–7], premature aging [8–11], the number of patients suffering from NAD is gradually increasing [7, 14–18], and the number of patients with multiple NAD is increasing year by year [7].
At the same time, some new research results only appeared in ILWH, and there is no literature to verify these phenomena for the time being. Therefore, we need to discuss these results.
1.The proportion of ILWH with both AD and NAD will increase year by year.
There may be three reasons to explain this result. Firstly, because most of ILWH were in the AIDS stage, their age was larger than that of the general HIV infected patients, so they were prone to opportunistic infections, and they were also prone to have NAD which was easy for the elderly. [43] Secondly, most of ILWH were hospitalized because of their serious condition. These patients were prone to suffer from AD and NAD at the same time because of their poor immunity [44]. Thirdly, due to the increase in the proportion of medical insurance reimbursements and the increase in the disposable income of the people in China in recent years, as well as the increase in the awareness of PLWH to seek medical treatment, most PLWH were willing to receive better treatment and care through hospitalization. These reasons have led to the increase in the proportion of patients with both AD and NAD, and have also created new challenges for the diagnosis, treatment and service capabilities of infectious disease hospitals.
2. The proportion of patients with fatal opportunistic infections is decreasing year by year, and TB is the fatal opportunistic infections disease with the highest proportion.
As China has expanded the scope of HIV testing for people at high risk of AIDS and the general population, many HIV-infected people can be detected early in HIV infection period and receive antiretroviral treatment, so that HIV-infected people will not progress to the AIDS stage, and reduce the probability of opportunistic infections. At the same time, with the continuous improvement of China's opportunistic infection prevention and control strategies (Including primary and secondary prevention(control) measures for opportunistic infections) for HIV-infected patients [36–41], it is reasonable that the proportion of fatal opportunistic infections in China has been declining year by year.
The reason why tuberculosis is the disease with the highest proportion is mainly because of the huge number of tuberculosis infections (disease savings pool) in China, which is expected to reach 350 million. These tuberculosis-infected people are likely to transmit Mycobacterium tuberculosis to HIV-infected people with low immunity. At the same time, when the body's immunity declines, the immune system can not control Mycobacterium tuberculosis nodules, and the pathogen will attack the body and spread to other organs. The incidence of this infection being activated is about 5–10% during the lifetime of latent tuberculosis infection (LTBI). Because the immunity of HIV-infected people is destroyed by HIV, their immunity is usually very poor, so they are more likely to activate LTBI.
3. Among all NAD, the proportion of metabolic syndrome has increased year by year, and has maintained the largest proportion. The increase in the proportion of ILWH with metabolic syndrome may be related to factors such as aging, the effects of antiretroviral drugs, chronic inflammation caused by HIV, and changes in the lifestyle of the Chinese population.
①From the results of this study, it can be seen that the aging of HIV hospitalized patients is more serious. The decline of body function due to aging increases the risk of ILWH suffering from metabolic syndrome.
②Antiretroviral drugs (such as integrase inhibitor Kelizhi [46]) may affect the metabolism of triacylglycerols in the body, leading to excessive accumulation of triacylglycerols in the body. The accumulation of triacylglycerol in liver cells can cause non-alcoholic fatty liver, the accumulation in muscle and pancreatic β cells may lead to insulin resistance and diabetes, and insulin resistance can cause hyperinsulinemia. Indinavir, a protease inhibitor in antiviral drugs, can cause insulin resistance and trigger hyperglycemia, while nucleoside drugs can cause insulin resistance through indirect effects such as fat redistribution.
③The impact of HIV can cause chronic inflammation in the body of an infected person. Chronic inflammation may lead to an increase in the amount of epicardial fat, and may lead to an increase in coronary calcium, myocardial perfusion defects and myocardial infarction. At the same time, HIV also affects pancreatic β-cell function and insulin secretion.[47]
④Due to changes in Chinese lifestyles, the average prevalence of overweight and obesity has risen from 5.3–20.5%[48], and obesity may be one of the causes of metabolic syndrome [49, 50]. According to statistics, among the top ten causes of death among Chinese residents, more than one-third of the diseases are related to metabolic syndrome[51], this may also be one of the reasons for the increase in the proportion of metabolic syndrome among ILWH.
4. Among the non-AIDS-defined diseases, hepatobiliary and pancreatic system diseases and blood system diseases account for a gradual decrease in the proportion of NAD. At the same time, the proportions of metabolic syndrome, kidney disease, gastrointestinal disease, NADM, bone disease and neurological disease are gradually increasing. The reasons for the changes in the proportion of metabolic syndrome have been explained above, and the changes in other diseases will be discussed next.
①The liver is the main metabolic site of most drugs used to treat opportunistic infections. The liver damage of PLWH in the early years was mainly caused by opportunistic infection diseases related drugs. With the gradual decrease in the proportion of PLWH with opportunistic infections, and the continuous improvement of drugs for the treatment of opportunistic infections, the damage to the liver is gradually reduced, resulting in a continuous decline in the proportion of ILWH with hepatobiliary and pancreatic diseases. [52, 53]
②The blood system disease spectrum established in this paper shows that the main blood diseases include anemia, pancytopenia, thrombocytopenia, agranulocytosis, and neutropenia. Most of these blood diseases are caused by HIV and are related to the physique of HIV-infected persons. As China has increased its efforts to screen for HIV, HIV-infected persons will be detected and treated in the early stages of infection. At the same time, most patients will pay attention to enhancing the body's nutrition and improving the body's immunity after knowing that they are infected with HIV. The above two reasons have led to a reduction in the incidence of blood system diseases.
③The increase in the proportion of kidney disease, gastrointestinal disease, neurological disease, and NADM may be related to immunodeficiency,the direct role of HIV-1, antiretroviral therapy toxicity, viral co-infections, behavioral risk factors, inflammation and ageing. Because the aging and low immunity of ILWH are more common, they are more susceptible to the above six factors and suffer from these NAD than ordinary HIV infected people. Many papers have demonstrated these reasons[17, 19, 54–62]. Studies have shown that NADM is the main cause of death among HIV-infected persons with NAD[7, 17, 22, 35], so early screening of HIV-inpatients is needed.
④Bone diseases include bone damage caused by external forces, as well as pathological bone diseases. The reasons for the increase in the proportion of bone diseases can be summarized in four points. Firstly, the effects of some antiretroviral drugs lead to changes in bone metabolism (such as tenofovir), which makes HIV-infected people suffer from bone diseases [63]. Secondly, because the immune system mediates a powerful effect on bone turnover, when the HIV virus destroys the human immune system, the HIV virus affects bone mass, causing osteoporosis or bone loss, thereby inducing the risk of fractures. [64, 65] Thirdly, due to the increasing aging in ILWH, the elderly have aging physical functions, weakened physical coordination and control capabilities, and are likely to cause bone damage due to falls. [66] Fourthly, as Chinese infectious disease hospitals have attached great importance to the bone mineral density examination of HIV-infected persons in recent years, most hospitals have purchased more advanced bone density testing equipment and discovered some unobvious bone diseases, which may also be the cause of the increase in bone diseases.
5. The proportion of ILWH with multiple types of NAD is increasing year by year
The human body is an extremely complex and precise structure. The various systems of the human body are connected, restricted and coordinated with each other to maintain the normal progress of various complex life activities inside and outside the human body and ensure the continuation of life. Due to the multiple effects of various systems of the human body, HIV and anti-HIV drugs, the body functions of ILWH may undergo some chain changes, resulting in ILWH suffering from multiple types of NAD.
If a certain system has dysfunction, it will affect the functions of other organs. For example, the kidney secretes 1,25-dihydroxyvitamin D3, which regulates calcium metabolism. Therefore, patients with chronic kidney disease may also suffer from renal bone disease; Decreased renal excretion function will increase cardiovascular load and cause cardiac insufficiency; Renal anemia further increases the burden of cardiovascular function and affects heart function; When patients with nephrotic syndrome have a hypercoagulable state of hypoproteinemia, they may be complicated by cardiovascular and cerebrovascular embolism and other cardiovascular and cerebrovascular diseases. Cardiac dysfunction affects pulmonary circulation, leading to pulmonary dysfunction and renal insufficiency. Therefore, when there is a problem with a certain system in an ILWH, they may suffer from more types of NAD due to their weaker body functions and immunity. [33]
6. Description of the data credibility
Since the prognostic data, medication data(Including antiretroviral therapy data and other and comorbidity therapy data), and medical inspection data(including CD4 + T lymphocyte count, HIV RNA viral load, liver and kidney function testing, etc.) in the database collected by the paper are not complete, we did not use these data in the prediction model, and only established the analysis and prediction model based on the ILWH case text data. This may have a certain impact on the prediction results of the model. However, we have verified that the prediction results of the model are credible through comparison with relevant literature, as well as adjustments and accuracy tests of the model.