Interpretation of Expert Consensus on Antiviral Therapy of COVID-19 / 中华临床感染病杂志

Novel coronavirus infection(COVID-19)has spread rapidly around the world since its emergence in 2019, with universal susceptibility of the population, causing hundreds of millions of infections and millions of deaths worldwide. Recently, the World Health Organization reconfirmed that COVID-19 is still a public health emergency of international concern. In order to ensure the early detection, identification and intervention of severe COVID-19 cases, reduce the disease severity and mortality, and further standardize the application of antiviral drugs for treatment, the National Center for Infectious Diseases (NCID) has invited experts to develop the Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( Trial version 10) in January 2023. The expert consensus is an important document that systematically reviews, summarizes and analyzes the application of antiviral drugs for COVID-19 from a multidisciplinary perspective for the first time, and can provide guidance and reference for medical institutions at all levels in the selection of antiviral drugs for COVID-19. This article aims to interpret the main points of the expert consensus, including the current epidemiological situation and pathogenic characters of novel coronavirus, clinical characteristics and classification of COVID-19, focusing on the antiviral therapy, guidance for home treatment and post-discharge management of patients with COVID-19.

Expert consensus on antiviral therapy of COVID-19 / 中华临床感染病杂志

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Research advances in antiviral drugs for the treatment of hepatitis D / 临床肝胆病杂志

Hepatitis D virus (HDV) is a satellite virus of hepatitis B virus (HBV) and needs the help of HBV envelope protein to complete its own assembly and replication and then establish a new infection cycle. Chronic HDV infection is considered the most severe form of viral hepatitis, which can accelerate disease progression and increase the risk of liver cancer. Effective antiviral therapy is urgently needed to delay disease progression in patients with HDV infection, but Bulevirtide conditionally approved by European Medicines Agency in July 2020 and interferon previously recommended are the only drugs used for the treatment of HDV infection. At present, studies are being conducted for several antiviral drugs targeting viral replication cycle, and early clinical trials have obtained good results. This means that important breakthroughs have been made in the development of antiviral drugs, bringing hope for the treatment of hepatitis D. This article summarizes the current antiviral drugs for hepatitis D and discusses related treatment regimens, so as to provide a reference for the treatment of hepatitis D.

Phase 1 safety and pharmacokinetics studies of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies

BackgroundBRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults. MethodsSingle ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days. ResultsAll infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development. ConclusionsBRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.

Spike mutations in SARS-CoV-2 variants confer resistance to antibody neutralization

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

Specific Dynamic Variations in the Peripheral Blood Lymphocyte Subsets in COVID-19 and Severe Influenza A Patients: A Retrospective Observational Study

BackgroundBoth COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. MethodsBy retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1- 4). ResultsWe reviewed the patients data of 110 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 43 severe influenza A. We found total lymphocytes (0.93 x109/L, 0.84 x109/L vs 1.78 x109/L, P < 0.0001) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of both severe patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). ConclusionsOur study indicates lymphopenia to be associated with disease severity and suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.

Expression and significance of Sirt1 in colorectal cancer / 中国医师进修杂志

Objective:Sirtuins family is involved in the regulation of many biological events in the cells of the body. As one of the important members, SIRT1 may participate in the formation and development of colorectal cancer. We detected the expression of SIRT1 in colorectal cancer and adjacent normal mucosa to explore its role and significance in the pathogenesis of colorectal cancer.Methods:One hundred and twenty surgical specimens of patients from Xinhua Hospital Affiliated to Dalian University who were hospitalized for colorectal cancer from January 2018 to July 2018 were selected as experimental group. The normal mucosa tissues more than 10 cm away from the tumor focus were taken as the control group. The expression of SIRT1 in colorectal cancer and normal mucosa was detected by immunohistochemistry SP method and Western blot. The different expression of SIRT1 in different organs of digestive tract and parts of human system was compared with Expression Atlas Database. The relationship between SIRT1 expression and clinical pathological data was analyzed to explore the role and significance of SIRT1 in colorectal cancer.Results:SIRT1 protein was mainly expressed in the tumor cell nucleus. The positive staining was brownish yellow, and it was highly expressed in rectal cancer; Sirt1 expression was positively correlated with the depth of tumor invasion, differentiation and tumor size, and the difference was statistically significant ( P<0.05); SIRT1 was highly expressed in human digestive tract, but there was no significant difference in the expression of SIRT1 in various organs of digestive tract; Sirt1 may function through the PI3K-AKT signaling pathway in colorectal cancer. Conclusions:SIRT1 plays the role of oncogene in the development of colorectal cancer, and increasing expression of SIRT1 promotes the development of colorectal cancer. SIRT1 may be a marker of early diagnosis of colorectal cancer, which is of great significance.

Detection rate of pathogens from sputum, blood, and bronchoalveolar lavage fluid samples in acquired immunodeficiency syndrome patients complicated with pulmonary infection / 中华传染病杂志

Objective To study the detection rate of pathogens from sputum , blood, and bronchoalveolar lavage fluid ( BALF ) samples in acquired immunodeficiency syndrome ( AIDS ) patients complicated with pulmonary infection.Methods Seventy-three hospitalized AIDS patients complicated with pulmonary infection in Beijing Ditan Hospital , Capital Medical University were enrolled from February 2018 to September 2018.Blood, sputum and BALF samples were collected.Blood samples were cultured to detect anaerobic bacteria, aerobic bacteria, fungi and mycobacteria.Antigen agglutination method was applied in blood samples to detect cryptococcus neoformans.The sputum samples were tested for Mycobacterium tuberculosis by acid-fast staining and were cultured to detect bacteria and fungi.The sputum samples were observed under microscope for sporotrichosis and fungal spores.The BALF samples were cultured to detect bacteria and fungi. The BALF samples were tested for Mycobacterium tuberculosis by polymerase chain reaction amplification and acid-fast staining.Pneumocystis were detected in BALF samples by methenamine silver staining method .The BALF samples were observed under a microscope for sporotrichosis and fungal spores .The detection rate of pathogens from blood, sputum and BALF samples were compared.Chi-square test was conducted for statistical analysis.Results In 73 AIDS patients complicated with pulmonary infection , the pathogen detection rates in blood, sputum and BALF samples were 8 (11.0%), 23 ( 31.5%) and 48 (65.8%), respectively.The difference was statistically significant ( F ＝48.513, P ＜0.01 ).The detection rate in BALF samples was significantly higher than that in blood or sputum samples ( χ2 ＝43.349 and 17.136, respectively, both P＜0.01).The detection rate in sputum samples was significantly higher than that in blood (χ2 ＝9.215, P＜0.05). The highest detection rates of pathogens in blood , sputum and BALF samples were Talaromyces marneffei 4.1%(3), viridans group streptococci 16.4%(12) and 35.6%(26), respectively.Conclusions The detection rate of pathogens in BALF samples from AIDS patients complicated with pulmonary infection is the highest , followed by sputum and blood samples.

We don't dare to tell her we don't know where to begin: Disclosure experiences and challenges among adolescents living with HIV and their caregivers in China.

BACKGROUND AND OBJECTIVES: With increasing access to antiretroviral therapy, HIV-infected youth are living longer, but are vulnerable as they navigate the transition to adulthood while managing a highly stigmatized condition. Knowing one's HIV status is critical to assuming responsibility for one's health. The process of disclosure to adolescents living with HIV is not well understood globally, even less so in China. To help address this gap, we explored practices for disclosure to adolescents living with HIV (ALHIV) among Chinese caregivers and clinicians, and the disclosure experiences of the adolescents themselves using qualitative methods. DESIGN AND SETTING: The study was conducted in 2014 at the Guangxi Center for Disease Control and Prevention ART (CDC-ART) clinic in Nanning, China. We used a qualitative design, incorporating in-depth interviews (IDIs) and focus group discussions (FGDs). PATIENTS AND METHODS: We conducted IDIs with 19 adolescent/caregiver dyads and five FGDs with adolescents and clinicians. Adolescent participants were aged 10-15 years, and had contracted HIV perinatally. Using NVivoTM software, we summarized major themes. RESULTS: Only 6/19 caregivers reported disclosing to their child; matched adolescents' statements indicate that 9/19 children knew their HIV status. Caregivers planned to disclose when children were 14 years or older. Concerns about stigma toward children and families were associated with reluctance to disclose. CONCLUSION: Disclosure to adolescents living with HIV in China was delayed compared with recommended guidelines. Culturally appropriate disclosure strategies should be developed, focused on supporting caregivers and de-stigmatizing HIV.

Expert consensus on the diagnosis and treatment of cryptococcal meningitis / 中华内科杂志

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

Differences and risk factors of regimen modification in acquired immunodeficiency syndrome patients who initiated antiretroviral treatment / 中华传染病杂志

Objective To compare the rates of regimen modification between patients with different initial antiretroviral therapy, and to investigate risk factors associated with drug toxicity-related regimen modification.Methods A two-years retrospective cohort study was conducted in 14 060 patients who initiated antiretroviral treatment with Zidovudine (AZT)/Tenofovir disoproxil (TDF)+Lamivudine (3TC)+Efavirenz (EFV) since 2012.There were 5 126 patients initiated TDF+3TC+EFV therapy (TDF group) and 8 934 patients initiated AZT+3TC+EFV therapy (AZT group).Chi-square test was used to compare the rate of first-line regimen modification and the rate of toxicity-related regimen modification between two groups.Cox proportional hazard model was used to investigate the risk factors associated with regimen modification.Results A total of 14 060 acquired immunodeficiency syndrome patients were observed for a median period of 1.85 person-years.There were 2 795 patients who changed their initial antiretroviral regimen and the rate of initial regimen modification was 19.9%.Two hundred patients who changed their initial regimen due to pregnancy were excluded.There were 2 070 patients in AZT group who changed their initial regimen with a rate of 23.5%.Among them, 1 652 patients changed their regimen due to drug toxicity and the rate was 18.8%.There were 525 patients in TDF group who changed their initial regimen with a rate of 10.4% and the rate of toxicity-related regimen modification was 6.2%.The differences between two groups were statistical significance (χ2=366.68 and 416.89, respectively, both P45 years old, BMI<18.5 kg/cm2 and baseline CD4+ T cell count<200/mL were risk factors associated with regimen modification.

Current status of anti-viral treatment in children with acquired immune deficiency syndrome in acquired immune deficiency syndrome care center, Yunnan / 中华传染病杂志

Objective To analyze the effect of long-term anti-viral treatment in children with acquired immune deficiency syndrome (AIDS) and investigate the factors affecting the treatment efficacy and growth and development of the children, so as to provide reference for improving the efficacy of antiviral drugs.Methods Children with AIDS receiving anti-retroviral treatment during 2004 to 2016 were retrospectively enrolled.The height, weight and CD4+ T cell counts were recorded every half year and the measurement of HIV RNA load was recorded on an annual basis.The CD4+ T cell counts and viral inhibition rates for the children who were under the treatment in the first year, 1~0.05);and viral inhibition rates were 92.9% and 97.6%, respectively with no statistical significance (χ2=1.071, P>0.05).The viral inhibition rate for the children receiving the treatment for 1 year was 85.7%, while that for whose treatment lasted for more than 10 years was 100.0%.A total of 5 cases developed drug-resistance (2 cases treated for 1 to 5 years and 3 cases for 5 to 10 years), and the virus replication was completely inhibited after switching to Lopinavir/ritonavir (LPV/r).The drug compliance was more than 95.0%.64.8% of children met the standard height, while 68.5% met the standard body mass.The baseline and last measured CD4+ T cell counts showed no significant differences between family-raised and social organization-raised children (Z=-1.159 and -0.523, respectively, both P>0.05).The children from high-income families had no significant differences compared with those from low-income ones in terms of the baseline and last measured CD4+ T cell counts (Z=-0.019 and -0.776, respectively, both P>0.05).Conclusions The long-term anti-retroviral treatment can effectively elevate the CD4+ T cell counts, inhibit viral replication and ensure drug compliance, which may promote the growth and development of children.However, approximately 30% children are still lower than the normal standards in terms of height and body mass.The drug-taking observer plays a central role on treatment effect.Most of the children′s family suffer from poor economic conditions.

Efficacy and safety of a raltegravir containing antiretroviral regimen among human immunodeficiency virus infected patients on methadone maintenance therapy / 中华传染病杂志

Objective To explore the efficacy and safety of a raltegravir (RAL)-containing regimen among patients on methadone maintenance therapy.Methods From January 2010 to November 2010, 30 virus (HIV) treatment naive patients who were on methadone maintenance therapy were enrolled from a HIV clinic in Kunming, Yunnan Province and a HIV clinic in Hengyang, Hunan Province.All patients were given RAL, tenofovir (TDF) and lamivudine (3TC) as highly active antiretroviral therapy (HARRT).Patients were followed up for 48 weeks to evaluate the adjustment of methadone dose, opiate withdrawal reaction, antiretroviral efficacy and safety.Results From January 2010 to November 2010, 30 HIV patients were enrolled from the two appointed HIV clinics.The mean age was 39±6 years, with 73.3% male patients and 97% Han population.Before the treatment, their mean CD4+T lymphocyte counts was 210 /μL.Ninety percent of patients were co-infected with hepatitis C.Twenty-nine patients who completed study follow-up were included in final analysis.Five (17.8%) patients reported opiate withdrawal symptoms and increased methadone dose 4 weeks after HARRT.At 24 weeks and 48 weeks of HARRT, the average increase of CD4+T lymphocyte counts were (136±71) /μL and (185±88)/μL, respectively.Among patients who provided valid HIV-1 RNA testing results, 82.6% (19/23) and 95.8% (23/24) of patients had undetectable viral load at week 24 and week 48.Six grade 1-2 adverse events were reported in 4 patients.Conclusions In this pilot study, the new regimen containing RAL, TDF and 3TC appears to be an ideal option for patients on methadone maintenance therapy, because of its limited impact on methadone dose and good efficacy and safety profile.

The effect of HIV infection and HAART on mitochondrion in peripheral monocytes / 中华检验医学杂志

Objective To evaluate the effect of HIV infection and highly active antiretroviral therapy (HAART) on mitochondrial function and mass in peripheral monocytes.Methods There were 14 ART-naive HIV-infected patients,14 NRTI treated HIV-infected patients and 12 healthy controls from Beijing Ditan Hospital.The mitochondrial membrane potential and mitochondrial mass in monocytes were analyzed by flow cytometry.Mitochondrial disturbances related to HIV infection and HAART in monocytes were analyzed.Results In ART-naive patients and NRTI-exposed patients,the levels of mitochondrial membrane potential in monocytes (77.74 ± 14.77,73.94 ± 12.87) were significantly lower than these in healthy controls (89.43 ±4.06) (P =0.032 8,P =0.002 6).The amount of mitochondrial mass in NRTI-exposed patients (3 329.0 ± 836.7) was significantly higher than that in healthy controls (2 075.0 ± 932.2) and that in ART-naive patients (2 592.0 ± 781.5) (P ＜ 0.05).Conclusions The abnormal of mitochondrial membrane potential and mitochondrial mass in monocytes from HIV-infected patients were related to HIV infection and the introduction of HAART.

Study on prevalence of malnutrition and related risk factors among human immunodeficiency virus -infected children in China / 中华传染病杂志

Objective To investigate the prevalence of malnutrition in human immunodeficiency virus ( HIV )‐infected children in China , and to explore and analyze the factors associated with malnutrition .Methods A cross‐sectional study was conducted by the antiretroviral treatment database of children .HIV‐infected children aged between 0 - 15 years old who initiated antiretroviral treatment were collected between January 1st , 2010 and December 31st , 2014 . Z‐score of height and weight were calculated by WHO Anthro (plus) software .Univariate and multivariate Logistic model analyses were performed to determine the factors associated with acute /chronic/mixed malnutrition .Results Baseline data of the 3 138 HIV‐infected children showed that 1 645 patients (52 .42% ) had malnutrition before antiretroviral treatment ,with acute ,chronic and mixed malnutrition of 8 .76% (275) ,39 .77% (1 248) and 3 .89% (122) ,respectively according to the type of malnutrition .Multivariate analysis showed that baseline CD4 + cell count < 200 cells/μL was the risk factor associated with acute malnutrition (aOR =2 .27 ,95% CI :1 .68 - 3 .06) ;rural settings (aOR = 1 .30 ,95% CI :1 .11 - 1 .53) ,baseline CD4 + cell count < 200 cells/μL (aOR = 1 .98 ,95% CI :1 .65 - 2 .38) ,baseline CD4 + cell count between 200 to 350 cells/μL (aOR = 1 .38 ,95% CI :1 .13 - 1 .69) and having AIDS‐related diseases (aOR = 1 .34 ,95%CI :1 .13 - 1 .59) were risk factors associated with chronic malnutrition ;and age of 11 - 15 years (aOR =2 .38 ,95% CI :1 .46 - 3 .88) ,baseline CD4 + cell count < 200 cells/μL (aOR = 4 .99 ,95% CI :3 .04 -8 .21) and having AIDS‐related diseases (aOR = 2 .45 ,95% CI :1 .65 - 3 .66) were risk factors associated with mixed malnutrition .Conclusions The prevalence of malnutrition in untreated HIV‐infected children remains high .All three types of malnutrition are associated with immunodeficiency .Early diagnosis and early treatment should be improved in HIV‐infected children through antiviral therapy to reduce the destruction of HIV to immune system .At the same time ,intensified monitoring of the nutritional status and nourishing undernourished children should be strengthened to reduce the prevalence of malnutrition .

Progress on China's national free antiretroviral therapy strategy in 2002-2014 / 中华流行病学杂志

Objective To analyze the progress and characteristics of China' s "Free AIDS treatment strategy" since the implementation of the national "four free and one care" policy against AIDS 12 years ago.Methods Retrospective cohort study and cross-sectional analysis had been conducted in this study.368 449 cases that had received the ‘free antiviral therapy’ from 2002 to 2014 were selected from the National Treatment Database.Data from the baseline (initial time of ART,CD4 cell count,and antiretroviral regimen) and from the follow-up program (dates and status of follow-up,CD4 cell counts) were gathered and analysed by SAS 9.3.Results The number of cases that having received new treatment was increasing year by year,accounting for 75.4％ of all the cases identified from 2010 to 2014.Constituent ratios of patients with baseline CD4 cell count ＜200 cells/μl and clinical diagnosis of AIDS were decreasing from 81.0％ in 2006 to 39.7 ％ in 2014.Status on drug optimization showed that:3TC replaced DDI,EFV replaced NVP and TDF replaced D4T,making the utilization rates as 99.5％,75.7％,and 60.6％,respectively,by 2014.Regions that were covered by the treatment accounted for 75.4％ of all the counties/districts involved.The previous CDC-led AIDS treatment program and mode of management had been transferred to the hospital-based model.Proportion on the twice-CD4-testing model had been 75.2％ since 2010,with the rate of virological detection increased from 70.8％ in 2010 to 87.4％ in 2014 and the virological unsuccessful testing rate decreased from 17.6％ in 2010 to 11.8％ in 2014.Among all the patients,the 1,5 and 10 year survival rates appeared as 92.2％,80.5％ and 69.6％,respectively.For patients with baseline CD4 cell counts as ＜50 cells/μl or ＞350 cells/μl,the corresponding survival rates showed as 81.6％,69.9％,60.9％ and 97.9％,89.8％,81.0％,respectively.Conclusion China's HIV/AIDS free anti-retroviral therapy program appeared as a national treatment cohort which involved large number of participants,with new patients joining in,annually.Criterion on drug optimization and treatment were consistently following the recommendation and guidelines set by WHO.Management program on treatment had gradually turned to hospital-based,with follow-up and laboratory testing programs guaranteed,ended up with satisfactory treatment effects.

Exploring stakeholder perceptions of facilitators and barriers to using needle exchange programs in Yunnan Province, China.

Injection drug use is an ongoing urban health crisis in China and one of the largest drivers of the transmission of HIV/AIDS. Sentinel surveillance sites in Yunnan province show upwards of 20% of injection drug users (IDUs) are HIV positive. Though the Ministry of Health has scaled-up needle exchange programs (NEPs), they have not received official government recognition nor have they been extensively evaluated to explore factors influencing their acceptability and feasibility. Using in-depth qualitative interviews conducted from February to July 2008 with 35 participants consisting of IDUs and other key stakeholders, we explored facilitators and barriers to accessing needle exchange programs in Kunming, the capital of Yunnan province. Content analysis was conducted to identify themes including attitudes toward NEPs and harm reduction, barriers to access, and suggestions for improvement. Themes that emerged included fears of breached confidentiality and police interference at the exchange sites and tensions between the public health and law enforcement perspective. Low levels of NEP-related knowledge and awareness were uniformly reported among interviewees. Suggestions to facilitate an increase in NEP acceptance included raising awareness of harm reduction and HIV more generally, offering services such as psychological counseling, job training and behavioral therapy at NEPs, and increasing communication between police, government, and public health officials. High rates of HIV infection among injection drug users in China have prompted rapid scale up of NEPs. Additional adaptations are necessary, however, to increase needle exchange use among injection drug users. This study finds that an urgent need to raise awareness of NEPs among policy makers and IDUs and act upon identified steps for developing social-structural interventions to create enabling environments that facilitate increased access to NEPs among injection drug users in Kunming.

The application of plasma drug monitoring in pediatric HIV/AIDS patient antiretroviral therapy adherence monitoring / 中华检验医学杂志

Objective To evaluate the application of plasma drug monitoring in pediatric HIV/AIDS patient antiretroviral therapy adherence monitoring.Methods Totally 261 plasma samples and related information were collected from three consecutive follow-up visits of 87 HIV-infected children treated in Shangcai county CDC of Henan province from March to October 2009.The plasma concentrations of antiretroviral drugs were measured by a developed high performance liquid chromatography-mass spectrometry method.Potential adherence influencing factors, such as regimen, age, gender, parent conditions, previous ART exposure and therapy duration, were analyzed by univariate logistic regression.Results Plasma concentration of antiretroviral drugs lower than LLTR (1 000 ng/ml) was the criteria to identify missed dose.The concentrations of 28 plasma samples were lower than LLTR, which meant missing dose.There were 17 patients (19.5%) with their concentrations lower than LLTR at least once in three follow-up visits.Logistic regression analysis of adherence related factors showed that compared with the children whose parents were both alive, the children whose mother and (or) father died were more likely to miss dose.The odds ratio was 4.13(95% credibility interval:1.37-12.46, P values was 0.012).Conclusions HIV-infected children have adherence problems when receiving antiretroviral therapy.Plasma therapeutic drug monitoring can be one of the effective methods to monitor the adherence.

Assessment of the effectiveness of highly active antiretroviral therapy in 1039 adult acquired immune deficiency syndrome patients in Dehong area, Yunnan Province / 中华传染病杂志

Objective To evaluate the effectiveness of free highly active antiretroviral therapy (HAART) in adult infected with human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) patients in Dehong area. Methods Clinical data of 1039 adult HIV/AIDS patients from five counties/cities in Dehong area who initiated HAART during the period from July 1st 2004 to June 30th 2008 were retrospectively analyzed to examine their virological and immunological responses to HAART. Data were analyzed by Chi-squared test or F test. Results Among the 1039 HIV/AIDS cases, 611 were males and 428 were females. The mean age was (37.0±9.9) years and the mean treatment duration was (22. 41 ± 12. 69) months. Complete viral suppression (HIV viral load＜50 copy/mL) was achieved in 781 cases (75. 17%). The percentage of patients achieving complete viral suppression rates were 76.95%, 76.49%, 70.65% and 77. 73% in patients treated for 6-12,13-24, 25-36 and more than 37 months, respectively (x2=8.646, P=0.194). The meanCD4+ T cell counts were (164.93±118.05) × 106/L at baseline, and (330.85±201.73) × 106/L, (356.24±205.49) × 106/L, (434.53±250.65) × 106/L and (396.31±202.62) × 106/L in patients treated for 6- 12, 13-24, 25-36 and more than 37 months, respectively. CD4- T cell counts were significantly different in patients treated for 6-12 and 13-24 months (F= 19. 423 , P＜0. 01). Successful immune reconstitution was achieved in 927 ( 90.88 % ) cases. Seven hundred and seventeen (70.29% ) cases achieved both virological suppression and immunological reconstitution with HAART, whereas 40 cases (3. 92%) failed to achieve both virological and immunological responses. Conclusion HIV/AIDS patients in Dehong area show good virological and immunological responses to HAART.

Development of multiple primer, HIV mini-pool NAT and its application in detecting acute infection of MSM / 中华检验医学杂志

Objective To establish a mini-pool nucleic acid testing (NAT) assay using multiplex RT-nested PCR for the detection of HIV RNA, and apply it in screening for acute HIV infection among MSM. Methods Frozen EDTA plasma samples collected between Oct. 2008 and Mar. 2009 from 3 HIV infectors during window-period, a total of 30 HIV chronically infected individuals and 97 healthy subjects were used to develop the NAT assay. Plasma samples from 10 cases were pooled into one tube and centrifuged at high speed for the collection of viruses. HIV RNA was extracted. Two pairs of primers were designed according to two conserved regions of HIV RNA ( HXB2 nt 5783-nt 6228 and nt 1235-nt 2012).Multiplex RT-PCR and nested PCR were performed. Individual NAT-reactive samples were confirmed by commercially available NAT assays. The sensitivity and performance efficacy were also evaluated. The assay was then applied to 1 005 plasma specimens from MSM with negative or uncertain HIV antibody test results.These were collected in the same period as the other samples. Results ( 1 ) Two fragments of HIV were amplified successfully with the low detection limit of 162 copies/ml plasma; (2) Results of the mini-pool HIV NAT validation with samples from 3 HIV infectors during window-period were consistent with the expected values; (3) All 30 plasma samples from MSM with positive HIV antibody, which were tested by multiplex RT nested PCR, were found to be HIV RNA positive; (4) One out of 1 005 plasma samples was found to be HIV RNA positive, for this case acute infection was followed-up and sero-conversion was found. Conclusion Mini-pool NAT has good sensitivity, and may be applied to screening HIV RNA among MSM during window-period.