The World Health Organization designates 1 December as World AIDS Day, and this year marks the 34th World AIDS Day under the theme "End inequalities. End AIDS. End pandemics. (Chinese theme: Life First, Ending AIDS, Health Equality.) )
AIDS, or acquired immunodeficiency syndrome (AIDS), is the causative agent of the human immunodeficiency virus (HIV), also known as HIV. AIDS is one of the most important public health problems affecting public health.
In 2005, the first edition of China's AIDS Diagnosis and Treatment Guidelines (hereinafter referred to as the Guidelines) was formulated, and updated in 2011, 2015 and 2018 respectively. This edition of the Guide is based on the fourth edition of the Guide in 2018 with reference to the latest research progress at home and abroad, and today we will study it together.
epidemiology
The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that by the end of 2020, there were 37.7 million living HIV/AIDS patients worldwide, 1.5 million new HIV infections that year, and 27.5 million people were receiving Antiretroviral therapy (ART). The United Nations Political Declaration on Ending the AIDS Epidemic by 2030, dated 8 June 2021, commits prevention as a priority to ensure that by 2025, effective integrated HIV prevention programmes cover 95% of those at risk of HIV infection, and commits to achieving the "three 95%" targets by 2030, i.e. 95% of HIV-infected people will be diagnosed, 95% of those diagnosed will have access to ART, and 95% of those receiving treatment will have their virus suppressed Commit to eliminate mother-to-child transmission of HIV by 2025, commit to limit the number of new HIV infections to less than 370,000 per year and control the annual DEATHS of AIDS to less than 250,000 by 2025, and eliminate all forms of STIG and discrimination related to HIV to achieve the goal of ending the AIDS epidemic by 2030.
Etiological features
HIV belongs to the human lentiviral group in the genus Lentiviridae of the retroviridae family, which is a spherical particle with a diameter of 100 to 120 nm, consisting of two parts: the core and the envelope. HIV is divided into HIV-1 and HIV-2. The HIV genome is about 9.7 kb long, and the long terminal repeat sequence (LTR) at both ends of the genome plays a role in regulating HIV gene integration, expression and viral replication. HIV is a highly variable virus with different degrees of variation in each gene, with the highest rate of variation in the env gene. HIV is less viable in the external environment and less resistant to physical and chemical factors. General disinfectants such as: iodine tincture, peracetic acid, glutaraldehyde, sodium hypochlorite and other effective disinfectants for hepatitis B virus (HBV), HIV also have a good inactivation effect. In addition, 70% alcohol can also inactivate HIV, but ultraviolet or γ rays cannot inactivate HIV. HIV is sensitive to heat and is more tolerant to low temperatures than high temperatures. Treatment at 56 °C for 30 min can make HIV lose infectivity to human T lymphocytes in vitro, but cannot completely inactivate HIV in serum; treatment at 100 °C for 20 min can completely inactivate HIV.
pathogenesis
HIV mainly invades the human immune system, including CD4+ T lymphocytes, monocytes macrophages and dendritic cells, etc., mainly manifested in the continuous reduction of the number of CD4+ T lymphocytes, which eventually leads to defects in human cellular immune function, causing various opportunistic infections and tumor occurrence. In addition, HIV infection can also lead to an increased risk of diseases such as cardiovascular disease (CVD), bone disease, kidney disease, and liver insufficiency.
Laboratory tests
Laboratory tests in HIV/AIDS patients mainly include HIV antibody detection, HIV nucleic acid qualitative and quantitative detection, CD4+ T lymphocyte count, AND HIV resistance testing, etc. HIV-1/2 antibody testing is the gold standard for hive infection diagnosis, and HIV nucleic acid detection (qualitative and quantitative) is also used in hive infection diagnosis. HIV antibody testing includes screening tests and supplemental tests, and HIV supplemental tests include antibody supplemental tests (antibody confirmation tests) and nucleic acid supplemental tests (qualitative and quantitative nucleic acid tests). HIV nucleic acid quantification and CD4+ T lymphocyte count are two important indicators for determining disease progression, clinical use, efficacy, and prognosis; HIV resistance testing can guide the selection and replacement of ART regimens.
Clinical manifestations and staging
From initial infection to terminal stage of HIV infection is a long and complex process, and the clinical manifestations associated with HIV are also diverse at different stages of the disease course. According to the clinical manifestations after infection, the whole process of HIV infection can be divided into three stages, namely the acute stage, the asymptomatic stage and the AIDS phase.
Acute phase
Hiv infection usually occurs within 6 months. Some infected patients present with clinical manifestations related to HIV viremia and acute injury to the immune system in the acute phase. Clinical manifestations are most common in fever, which may be accompanied by sore throat, night sweats, nausea, vomiting, diarrhea, rash, joint pain, lymphadenopathy, and neurologic symptoms. Most patients have mild clinical symptoms that resolve spontaneously after 1 to 3 weeks.
HIVRNA and p24 antigens can be detected in the blood at this stage, the CD4+ T lymphocyte count is transiently decreased, and the CD4+/CD8+ T lymphocyte ratio is inverted. Some patients may have mild leukopenia and thrombocytopenia or abnormal liver biochemical markers.
Asymptomatic period
This phase can be entered from the acute phase or directly without obvious acute phase symptoms. The duration is generally 4 to 8 years. The length of time is related to the number and type of infection with the virus, the route of infection, individual differences in the body's immune status, nutritional conditions and living habits. During the asymptomatic phase, the CD4+ T lymphocyte count gradually decreases as HIV continues to replicate in the infected person and the immune system is impaired. Symptoms or signs such as lymphadenopathy may be present.
AIDS phase
It is the terminal stage after HIV infection. Patients with CD4+ T lymphocyte counts < 200 cells/microlitre. The main clinical manifestations of this stage are HIV-related symptoms and signs, as well as various opportunistic infections and tumors.
Antiviral therapy
Therapeutic goals
Maximum inhibition of viral replication reduces viral load to the lower limit of detection and reduces viral variation; re-establish immune function; reduces abnormal immune activation; reduces virus transmission and prevents mother-to-child transmission; reduces the incidence and mortality rate of HIV infection, reduces the incidence and mortality rate of non-AIDS-related diseases, and enables patients to obtain normal life expectancy and improve quality of life.
Introduction of existing antiretroviral drugs in China
At present, there are more than 30 drugs in six major categories, namely nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INS⁃TIs), fusion inhibitors (FIs) and CCR5 inhibitors. Domestic antiretroviral therapy drugs have five categories of NRTIs, NNRTIs, PIs, INSTIs and FIs (including compound preparations), see Table 2.
Antiviral therapy for adults and adolescents
The recommended regimen for treating patients is 2 NRTIs combined with class III drugs. The third class of agents may be NNRTIs or enhanced PIs (including ritonavir or cobistat) or INSTIs, or combination monolithic formulations (STR) may also be used. Based on the antiviral drugs available in China, the recommended and alternative options for ART in adult and adolescent first-treated patients are shown in Table 3.
Antiviral therapy in children
Once HIV infection is confirmed in children, it is recommended to start ART immediately, regardless of CD4+ T lymphocyte levels. If art cannot be initiated for some reason, the patient's virology, immunology, and clinical condition need to be closely observed, and monitoring is recommended every 3 to 4 months. The recommended regimen for initial treatment in pediatric patients is 2 NRTIs in combination with class 3 drugs. The third class of drugs can be INSTIs or NNRTIs or enhanced PIs (including ritonavir or corbistat), based on the current clinical practice in China, the recommended specific regimens are shown in Table 4.
Antiviral therapy for lactating women
Breastfeeding carries a risk of HIV transmission and hive-infected mothers should avoid breastfeeding as much as possible, especially for mothers whose viral load is still detectable, and breastfeeding is not recommended. If breastfeeding is insisted, art should continue throughout lactation, the protocol is consistent with the ART regimen during pregnancy, and the newborn stops breastfeeding immediately after 6 months of age.
Methadone maintenance in intravenous drug dependence
Intravenous drug dependence should start art at the same time as ordinary patients, but it should be noted that drug addiction will affect the patient's medication compliance, so the importance of adherence to the success or failure of treatment should be fully explained to patients before starting ART, and try to use a simple treatment regimen, fixed dose combination regimen, and those with conditions can consider preferring art regimens containing RAL or DTG or BIC. Continuous monitoring of drug distribution is effective in improving compliance. In addition, attention should be paid to the interaction between antiviral drugs and methadone.
People with HBV infection
Initiation of ART is recommended as early as possible, regardless of CD4+ T lymphocyte levels, as long as there is no indication of anti-HIV suspension therapy. (1) HIV/HBV co-infected patients should be treated with two viral infections at the same time, including two anti-HBV active drugs, art regimen nucleoside drug selection recommended TDF (or TAF) + 3TC (or FTC), (of which TDF + FTC, TDF +3TC, TAF + FTC all have a combination of dosage forms), but the incidence of nephrotoxicity and osteoporosis caused by TAF is lower than TDF. (2) In the process of treatment, HBV-related indicators such as HBVDNA quantification, liver biochemistry, liver imaging, HBV resistance, etc. should be monitored to be vigilant against the occurrence of cirrhosis and hepatocellular carcinoma. (3) For HIV/HBV co-infection, it is not recommended to choose a regimen containing only 1 nucleoside drug active to HBV (TDF, 3TC, entecavir, telbivudine, adefovir) to treat hepatitis B to avoid inducing HIV resistance to nucleoside drugs.
AIDS-related tumors
AIDS-related tumors mainly include non-Hodgkin lymphoma and Kaposi sarcoma, and also need to pay attention to the screening, diagnosis and treatment of non-HIV-defining tumors such as liver cancer, lung cancer, and perianal tumors. Diagnosis of the tumor depends on pathological biopsy.
Treatment requires individualized combinations of treatment, including surgery, chemotherapy, targeted therapy, immunotherapy, interventional therapy, and radiation therapy. All patients with AIDS with tumors are advised to start ART as early as possible, pay attention to the interaction between antiviral drugs and antineoplastic drugs, and try to use ART regimes with small myelosuppressive effects and drug-to-drug interactions, such as regimes containing INSTs or FIs. The diagnosis and treatment of tumors should not reduce the requirements due to HIV infection, the application of multidisciplinary cooperative diagnosis and treatment (MDT) mode should be advocated, and the diagnosis and treatment plan should be formulated together with experts in oncology, interventional medicine, pathology, surgery and so on. Attention is paid to preventing various complications, especially the occurrence of infections, during treatment.
Management of HIV exposure and prevention of blockade
Post-exposure prophylaxis (PEP) refers to the biological method of reducing the risk of HIV infection by taking specific anti-HIV drugs as early as possible (no more than 72 hours) after exposure to a high risk of infection, such as a clear body fluid exchange behavior with an HIV-infected person or a person with an unknown status of infection. HIV exposure is divided into two parts: occupational exposure and non-occupational exposure.
Full management of HIV infection
The emergence and application of ART has greatly reduced AIDS-related opportunistic infections and tumors, turning AIDS into a chronic disease that can be treated but is currently difficult to completely cure, and with the prolongation of the survival of HIV/AIDS patients, the incidence of various non-AIDS defining diseases (NAD) such as metabolic syndrome, cardiovascular and cerebrovascular diseases, chronic hepatic and renoskeletal diseases and non-AIDS defining tumors has shown an upward trend. These diseases have become a major cause of quality of life and prognosis for HIV/AIDS patients in the post-ART era.
The changes brought about by ART in the disease spectrum are also changing the diagnosis and treatment and care patterns of HIV/AIDS patients. The whole process of HIV infection management refers to a comprehensive diagnosis and treatment and service care management model provided by the patient's multidisciplinary cooperation team after confirming HIV infection. The focus of the whole process of management mainly includes: (1) prevention and early diagnosis of HIV infection; (2) diagnosis and treatment of opportunistic infections; (3) initiation and follow-up of individualized antiviral therapy, adherence to medication education and supervision; (4) screening and treatment of non-AIDS-defined diseases; (5) comprehensive psychosocial care. The full management of HIV infection is a multidisciplinary collaborative model led by infectious disease physicians.
Reference: Chinese Medical Association Infectious Diseases Branch AIDS Hepatitis C Group, Chinese Center for Disease Control and Prevention. Guidelines for the Diagnosis and Treatment of HIV/AIDS in China (2021 Edition).