Source: Chinese Journal of Infectious Diseases, 2024,42: Online pre-publication.
In 2005, the AIDS Hepatitis C Group of the Infectious Diseases Branch of the Chinese Medical Association formulated the Guidelines for the Diagnosis and Treatment of AIDS in mainland China (hereinafter referred to as the "Guidelines"), and the 2024 version of the Guidelines is revised on the basis of the 5th edition of the Guidelines in 2021 with reference to the latest research progress at home and abroad. The new version of the Guidelines focuses on antiviral therapy, whole-process management, opportunistic infections, human immunodeficiency virus (HIV) complicated with tumors, and the prevention and intervention of HIV infection.
This article only elaborates on the recommendations of the guide, and interested readers can click [Read the original article] to read the full text for free.
1. Epidemiology
Recommendation 1: For spouses and sexual partners of HIV/AIDS patients, intravenous drug dependents who share syringes with HIV/AIDS patients, children born to HIV/AIDS patients, and clinical patients with high-risk behaviors and/or clinical symptoms suspected of HIV infection, health care providers should proactively provide HIV-related testing and appropriate counseling services (C1).
3. Laboratory testing
Recommendation 2: Patients with a positive HIV screening test should be further confirmed to confirm HIV infection (A1) by supplemental testing, including antibody supplementation tests (HIV-1/2 antibody confirmatory tests) and nucleic acid supplementation tests (qualitative and quantitative HIV-1 nucleic acid tests).
Recommendation 3: Genotypic resistance testing should be performed in treatment-naïve HIV patients prior to initiation of ART. Integrase gene mutation testing (C1) should be performed in patients with newly diagnosed HIV infection or who remain infected with HIV despite PrEP with CAB-LA and are considered to be resistant to INSTI.
6. Diagnostic criteria
Recommendation 4: The whole process of HIV infection can be divided into three stages, namely the acute phase, the asymptomatic phase and the AIDS phase; The diagnosis of HIV/AIDS should be based on a comprehensive analysis of the epidemiological history, clinical manifestations, and laboratory test results, and the diagnosis should be made with caution and clinical staging (A1).
7. Common opportunistic infections
(一)PCP
Recommendation 5: SMZ-TMP is the first choice for the treatment of PCP, trimethoprim 15~20 mg·kg-1·d-1, SMZ 75~100 mg·kg-1·d-1, divided into 3~4 times, and the course of treatment is 21 days; Critically ill patients (PaO2<70 mmHg or alveolar-arterial oxygen partial pressure difference >35 mmHg) can be treated with glucocorticoids (prednisone or intravenous methylprednisolone) in the early stages (within 72 hours) for a total duration of 21 days (A1).
Recommendation 6: HIV/AIDS patients with CD4+ T lymphocyte count < 200/μL should use SMZ-TMP for PCP prophylaxis with 1 tablet per day for primary prevention and 2 tablets per day for secondary prevention; Prophylactic medication (A1) can be discontinued after ART when the CD4+ T lymphocyte count increases to >200/μL and lasts for ≥ 3~6 months.
(2) Tuberculosis
Recommendation 7: Patients with HIV/AIDS should be systematically screened for tuberculosis at each visit, and clinical attention should be paid to the possibility of systematic screening for tuberculosis in combination with medical history, typical symptoms and signs of tuberculosis, and imaging and laboratory tests (B1).
Recommendation 8: The principle of treatment of tuberculosis in patients with HIV/AIDS is the same as that of ordinary tuberculosis patients, but the interaction with antiviral drugs and the contraindications should be paid attention to when using anti-tuberculosis drugs (A1).
Recommendation 9: All HIV/AIDS patients with TB should receive ART as soon as possible, regardless of CD4+ T lymphocyte count levels, and it is recommended to initiate ART as soon as possible within 2 weeks of antituberculosis therapy. For patients with drug-resistant tuberculosis, ART is started within 8 weeks of second-line anti-tuberculosis drugs; For patients with central nervous system tuberculosis, it is generally recommended to start ART (C1) 4~8 weeks after anti-tuberculosis, and for patients with AIDS and tuberculous meningitis treated with glucocorticoids, it is recommended to start ART within 2 weeks after starting anti-tuberculosis therapy.
(3) NTM infection
Recommendation 10: HIV/AIDS with NTM infection is predominantly MAC infection, and the diagnosis of MAC disease depends on the culture of MAC (A1) from the patient's blood, lymph nodes, bone marrow, and other sterile tissues or body fluids.
Recommendation 11: The preferred pathogen treatment regimen for MAC disease is: clarithromycin 500 mg/time, 2 times/d (or azitoxin 500 mg/d) + ethambutol 15 mg·kg-1·d-1, and rifabutin (300~600 mg/d). Patients with severe infection and severe immunosuppression (CD4+ T lymphocyte count <50/microlitre) may be treated with amikacin (10 mg/kg-1/d-1 intramuscularly once daily) or a quinolone antimicrobial such as levofloxacin or moxifloxacin (B1). Treatment is usually at least 12 months. ART (B1) is initiated as soon as 2 weeks after initiation of antiMAC therapy.
(4) CMV infection
Recommendation 12: The diagnosis of CMV retinitis depends on ophthalmoscopy, and the treatment can be ganciclovir, valganciclovir, and foscarnet sodium, and the course of treatment is 2~3 weeks; Local treatment: intravitreal ganciclovir or foscarnet, repeated once a week, until retinopathy is controlled and the lesion is inactive (A1).
Recommendation 13: Primary prophylaxis of CMV infection is not recommended in patients with HIV/AIDS. The first choice of secondary prevention is gamciclovir (1.0, 3 times/day, oral), and discontinuation of secondary prevention (B1) can be considered when the CD4+ T lymphocyte count is > 100/μL and lasts for more than 3~6 months.
(6) Toxoplasmosis encephalopathy
Recommendation 14: Pyrimethamine (loading dose of 100 mg, oral, 2 times/d, followed by 50~75 mg/d) + sulfadiazine (1~1.5 g, oral, 4 times/d) is preferred for the treatment of toxoplasmosis encephalopathy, and alternative therapy: SMZ-TMP (3 tablets, 3 times a day) combined with clindamycin (600 mg/time, intravenous administration, every 6 hours) or azithromycin (0.5 g/d). The course of treatment is at least 6 weeks (A1).
Recommendation 15: SMZ-TMP (2 tablets once a day) should be used to prevent toxoplasmosis encephalopathy (B1) in HIV/AIDS patients with HIV/AIDS who have a CD4+ T lymphocyte count of < 200/microL and are positive for Toxoplasma IgG antibodies. After receiving ART, the CD4+ T lymphocyte count increases to >200/μL for 3 months for > 3 months, and prophylaxis can be discontinued (A1); or CD4+ T lymphocyte count is 100~200/μL after ART, and the viral load is consistently lower than the lower limit of detection for 3~6 months, and prophylactic medication (B1) can also be considered.
Recommendation 16: For patients who have suffered from toxoplasmosis encephalopathy in the past, long-term use of pyrimethamine (25~50 mg/d) combined with sulfadiazine (2~4 g/d) for prophylaxis until the CD4+ T lymphocyte count increases to >200/μL for ≥ 6 months (A1). Once the CD4+ T lymphocyte count drops to <200/microlitre, prophylaxis (C1) should be restarted.
(vii) Fungal infections
Recommendation 17: The treatment of pathogens in HIV/AIDS complicated with cryptococcal meningitis is divided into three stages: induction phase, consolidation phase and maintenance phase, and amphotericin B (0.5~0.7 mg·kg-1·d-1) or L-AMB (3~4 mg·kg-1·d-1) + flucytosine (100 mg·kg-1·d-1) is preferred in the induction period for at least 6 weeks in the induction period and fluconazole (600~800 mg/d) is preferred for at least 6 weeks in the consolidation phase. Fluconazole (200 mg/day) was selected for the maintenance period for at least 1 year, and the drug can be discontinued until the CD4+ T lymphocyte count > 100/microL after ART is continued for at least 6 months (A1).
Recommendation 18: A single dose of L-AMB 10 mg/kg combined with flucytosine (100 mg·kg-1·d-1) and fluconazole (600~800 mg/d) for 2 weeks (A1) can be preferred for the induction period of HIV/AIDS combined with cryptococcal meningitis.
Recommendation 19: ART (A1) should be initiated after 4~6 weeks of regular anti-cryptococcal therapy in patients with HIV/AIDS and cryptococcal meningitis.
Recommendation 20: HIV/AIDS patients with cryptococcal antigenemia are recommended to be given fluconazole 400~800 mg/d orally for 10 weeks, and then changed to 200 mg/d oral prophylaxis, with a total course of 6~12 months (C1).
Recommendation 21: Amphotericin B (0.5~0.7 mg·kg-1·d-1) or L-AMB (3~5 mg·kg-1·d-1) or amphotericin B cholesterol-sulfate complex (3~4 mg·kg-1·d-1) or amphotericin B cholesterol-sulfate complex (3~4 mg·kg-1·d-1) is preferred for antifungal treatment in the induction phase of HIV/AIDS combined with marneffei carnicosis for 2 weeks (A1); The continuation phase is oral itraconazole or voriconazole 200 mg every 12 hours for 10 weeks; This is followed by secondary prophylaxis with itraconazole 200 mg orally once a day (B1) until the patient's CD4+ T lymphocyte count > 100/microL after ART, and can be discontinued for at least 6 months (B1). Once the CD4+ T lymphocyte count < 100/microL, prophylaxis (C1) needs to be restarted.
8. Antiviral therapy
(3) Timing and regimens of antiviral therapy for adults and adolescents
1. When to start ART in adults and adolescents:
Recommendation 22: Early initiation of ART is recommended for all HIV infections, regardless of CD4+ T lymphocyte levels, to reduce morbidity and mortality and prevent HIV transmission (B1); Patients with conditions are advised to start ART quickly (within 7 days after diagnosis) or on the same day of diagnosis (A1).
2. Initial ART program for adults and adolescents:
Recommendation 23: The recommended ART regimen for treatment-naïve adults usually consists of two NRTI backbone drugs combined with a third class of drugs, and the third class of drugs can be INSTI or NNRTI or enhanced PI (including ritonavir or cobicistat); STR (A1) is also available; For treatment-naïve patients with HBsAg-negative viral loads <of 5×105 copies/mL, dolutegravir/lamivudine ART (A1) may be preferred.
(4) Antiviral treatment for special populations
1. Children:
Recommendation 24: ART (B1) is recommended for children as soon as HIV infection is confirmed, regardless of CD4+ T lymphocyte levels.
Recommendation 25: The ART regimen for treatment-naïve children is recommended as two NRTI backbone drugs combined with class III drugs, and the third class drugs can be INSTI or NNRTI or enhanced PI (including ritonavir or cobicistat) (B1).
4. Patients with Mycobacterium tuberculosis infection:
Recommendation 26: The recommended preferred ART regimen for patients with HIV/AIDS and tuberculosis is tenofovir (zidovudine) + lamivudine (emtricitabine) + efavirenz or dolutegravir (A1), and when combined with rifampicin, the dose of dolutegravir is recommended to be doubled (50 mg twice daily) (A1).
6. Joint HBV infected persons:
Recommendation 27: Patients with HIV/HBV co-infection are recommended to initiate ART as soon as possible, regardless of CD4+ T lymphocyte count level, and the ART regimen should include 2 antiviral drugs with anti-HBV activity, and the nucleoside drugs in the backbone of ART recommend tenofovir (or TAF) + lamivudine (or emtricitabine) (B1).
7. Patients infected with HCV:
Recommendation 28: Patients with HIV and HCV infection should initiate ART and active anti-HCV therapy as soon as possible, and the regimen and duration of anti-HCV therapy should be the same as that of patients with HCV infection alone, and the interaction with ART drugs should be noted (A1).
(5) Monitoring of antiviral therapy
Recommendation 29: After starting ART, it is recommended to conduct virology, immunology and clinical follow-up every 3~6 months to evaluate the efficacy of ART, and timely detect the adverse reactions of antiviral drugs and whether there is viral resistance, so as to change the drug in time and ensure the success of ART (C1).
(7) Drug interactions
Recommendation 30: Viral load testing is recommended as the preferred method for detecting and confirming antiviral therapy failure (C1); Once antiretroviral therapy failure is confirmed, HIV resistance testing (C1) should be performed as soon as possible.
Recommendation 31: In the event of virological failure, the patient's adherence to treatment, drug-drug or drug-food interactions should be assessed first, especially as medication adherence is a determinant of treatment success or failure. Patients with ART failure should be adjusted according to the results of HIV drug resistance testing, and the principle of regimen selection is to change at least 2 ART drugs, preferably 3 drugs with antiviral activity; New ART regimens should typically include 1 enhanced PI or INSTI with full antiviral activity or a new mechanism of action drug that has not been used before, such as capsid inhibitors and FI, or a combination of these drugs (A1).
Recommendation 32: LLV needs to assess patient adherence, tolerability, and adverse drug reactions, and drug interactions (A1). LLV usually does not require a change in treatment regimen (B1), but HIV RNA monitoring is required every 3 months to assess the need for adjustment to the ART regimen (C1).
九、IRIS
Recommendation 33: The possibility of IRIS should be considered when HIV-infected patients develop inflammation-related manifestations such as fever, latent infection becoming active, and exacerbation or exacerbation of pre-existing infection after receiving ART, but care should be taken to exclude HIV disease progression, new infection, HIV-related tumors, adverse drug reactions, and treatment failure. Treatment of the associated opportunistic infection should be started or continued clinically, depending on the severity of IRIS, and in severe cases, glucocorticoids or nonsteroidal anti-inflammatory drugs (C1) may be used for a short period of time.
10. Immune function insufficiency
Recommendation 34: Immune reconstitution insufficiency (B1) should be considered if the peripheral blood viral load is lower than the lower limit of detection (<50 copies/mL) for more than 3 years, and the CD4+ T lymphocyte count remains below 350/microlitre, and other causes that may lead to a chronically low CD4+ T lymphocyte count are excluded.
Recommendation 35: There is a lack of clear and effective treatment for immune reconstitution, and regular clinical monitoring should be carried out, and prevention of opportunistic infections and screening for NADE should be performed according to CD4+ T lymphocyte levels. For patients who have achieved virologic suppression, haphazard ART adjustment for improved immune reconstitution (B1) is not recommended.
11. AIDS-related tumors
Recommendation 36: Patients with HIV should be screened for AIDS-defining tumors and non-AIDS-defining tumors during follow-up. Women over the age of 25 with HIV are advised to undergo regular cervical cancer screening (C1). All patients with AIDS and tumors are advised to initiate ART as soon as possible, pay attention to the interaction between antiviral drugs and antineoplastic drugs, and choose ART regimens with low myelosuppressive effect and drug interactions. The MDT model is advocated to provide standardized care (C1) for patients with HIV and cancer.
12. Interruption of mother-to-child transmission of HIV and childbirth in single-yang families
(1) Antiretroviral drug intervention
Recommendation 37: All HIV-infected pregnant women should receive ART (B1) as early as possible and for life, regardless of their CD4+ T lymphocyte count or clinical stage of disease; Triple ART regimens containing dolutegravir or raltegravir are preferred for ART in pregnant women (A1).
Recommendation 38: Infants born to HIV-infected mothers should be given antiviral prophylaxis as soon as possible (within 6 hours) after birth, and the regimen should be determined according to the risk of exposure (B1).
(3) Postpartum feeding guidance
Recommendation 39: Recommend scientific feeding for infants born to HIV-positive mothers, avoid breastfeeding, and eliminate mixed feeding (A1); For infected mothers and their families who choose to breastfeed because they do not have the conditions for artificial feeding, they should be fully counseled and informed, and they should be guided to adhere to correct exclusive breastfeeding, and must adhere to ART throughout the lactation period, and the feeding time should not exceed 6 months (A1).
13. Prevention and blockade of HIV before and after exposure
(一)PEP
Recommendation 40: HIV RNA testing is recommended prior to HIV prophylaxis blockade, especially for seekers with a prior history of blockade (A1); Prophylactic medication should be given for the shortest possible time (as soon as possible within 2 hours) after HIV exposure, preferably within 24 hours but no more than 72 hours, for 28 days (C1); The post-exposure blockade regimen is preferred with FTC/TDF (or FTC/TAF) plus INSTI (BIC or dolutegravir or raltegravir) (C1).
(二)PrEP
Recommendation 41: HIV exposure risk assessment and medical and adaptive assessment (C1) should be done before the implementation of PrEP, and there are two oral regimens for PrEP, namely daily and event-driven regimens, and the drugs can be FTC/TDF (or FTC/TAF) (A1); For those who cannot choose oral drugs, an intramuscular regimen of CAB-LA can be used (A1).
14. Full management of HIV infection
Recommendation 42: All patients living with HIV are recommended to be managed according to a whole-course management model (C1).
Recommendation 43: Screening for various opportunistic infections should be performed in patients with HIV infection who are detected late, especially those in the advanced stages of HIV infection, and screening for tuberculosis and cryptococcosis should be a routine clinical diagnosis and treatment (A1).
Recommendation 44: Serum CrAg screening is recommended in HIV-infected patients with CD4+ T lymphocyte counts <200/microL, and cerebrospinal fluid examination should be performed in positive cases to rule out cryptococcal meningitis (B1).
Recommendation 45: Before initiating ART, it is recommended to perform corresponding baseline testing and evaluation, including HIV RNA, CD4+ T lymphocyte count, HIV drug resistance testing, blood routine, urine routine, liver and kidney function, blood glucose, blood lipids, and whether there are co-infections (such as viral hepatitis, cryptococcosis, tuberculosis, STIs, etc.) (C1).
Recommendation 46: Special attention should be paid to the issues related to antiviral therapy and follow-up in vulnerable populations, including elderly patients over 50 years of age, pediatric patients, pregnant women, patients with multiple underlying diseases, patients with highly immunosuppressed diseases such as CD4+ T lymphocyte count <50/μL, and patients with immune reconstitution insufficiency after ART. Such patients should be more aggressive in ART, actively treat the underlying disease, and pay attention to multidisciplinary diagnosis and treatment (C1).
Recommendation 47: For patients with effective viral suppression after ART, it is not recommended to adjust the treatment regimen at will. Optimisation of treatment should be based on maintenance of viral suppression and should not pose a threat to future drug choices. When optimizing the ART regimen, special attention should be paid to the presence of HIV resistance and the presence or absence of HBV or HCV infection (A1); HIV-infected patients who are virologically suppressed and have no history of transmissible or acquired HIV resistance can usually be switched to any preferred recommended initial ART regimen and virologically suppressed (A1).
Recommendation 48: All patients living with HIV should receive regular CVD risk assessment, screening, and prophylaxis interventions, and for patients at high CVD risk, ART regimens should be adjusted accordingly, while relevant CVD risk factors such as smoking cessation, blood glucose, blood lipids, obesity, and blood pressure should be actively controlled (C1).
Recommendation 49: Conditions should be created to facilitate access to care services for people living with HIV/AIDS and to ensure the sustainability of health services (B1); Vaccination guidance (C1) should be given to patients with HIV/AIDS.
Source: Chinese Medical Journal Network