Expansion of China’s free antiretroviral treatment program

Background  In 2003, China’s National Free Antiretroviral Treatment Program (NFATP) was initiated as a pilot, which covered only 100 HIV/AIDS patients. By 2011, the pilot had evolved into a nationwide program and had provided free treatment for over 150 000 patients. The objective of this study was to report and evaluate the progress of China’s free antiretroviral treatment program.

Methods  The NFATP Database was systematically reviewed and a total of 150 692 HIV/AIDS patients were included in this study. Program progress indicators including the number of treated HIV/AIDS patients, follow-up visit rate, CD4 test rate, and viral load test rate were summarized and examined over a calendar year to evaluate the progress of NFATP quantitatively and qualitatively.

Results  By the end of 2011, a total of 150 692 HIV/AIDS patients had been treated through the NFATP and 122 613 of them were still on treatment. Of all patients, about 72% were enrolled during the past four years. The dominant transmission route was blood related in the early phase of the NFATP, but gradually changed to sexual contact. Besides quantitative improvements, progress indicators also demonstrated significant qualitative improvements that the program had made during the past 9 years.

Conclusions  Great achievement has been made by China’s NFATP. China’s experience indicates the importance of a comprehensive response to the success of its treatment program. However, to ensure the quality and sustainability of treatment in the long term, more attention and resources should be paid towards program management.

     

New policies and strategies to tackle HIV/AIDS in China

Over the past decade, China has made remarkable progress in promoting universal access to HIV prevention, treatment and care and support. As a result, overall AIDS mortality among treatment eligible patients dropped 63.9% between 2002 and 2009. However, many key challenges remain in the early identification of HIV-positive individuals and timely provision of antiretroviral treatment (ART). To address these challenges, the Chinese government has taken steps to translate the latest scientific research findings into its newly issued national AIDS policy and strategy. China’s recent adoption of “Treatment as Prevention” to reduce HIV incidence and HIV/AIDS related morbidity and mortality is intended to help achieve the United Nations Millennium Development Goals by 2015.

     

HIV/AIDS患者抗逆转录病毒治疗退出影响因素研究进展

艾滋病是由人类免疫缺陷病毒(H1V)引起的一种危害性极大的传染病,需要HIV/AIDS患者每日按时按量服药才能有效抑制体内HIV复制.中国实施抗逆转录病毒疗法(ART)和扩大治疗策略将所有符合条件的HIV感染者纳人治疗范围,越来越多的HIV感染者接受ART,同时退出(停药和失访)ART的HIV/AIDS患者人数也在逐年...     

Human Immunodeficiency Virus Infection-Associated Mortality during Pulmonary Tuberculosis Treatment in Six Provinces of China

Objective To investigate the risk factors attributable to tuberculosis-related deaths in areas with human immunodeficiency virus (HIV) infection epidemics.
Methods A prospective cohort study of newly registered patients in tuberculosis (TB) dispensaries in six representative Chinese provinces was conducted from September 1, 2009 to August 31, 2011. Risk factors for TB-associated death were identified through logistic regression analysis.
Results Of 19,103 newly registered pulmonary TB patients, 925 (4.8%) were found to be HIV-positive. Miliary TB and acid-fast bacillus smear-negative TB were more common among these patients. Out of a total of 322 (1.7%) deaths that occurred during TB treatment, 85 (26%) of the patients were co-infected with HIV. Multivariate analysis revealed that HIV infection was the strongest predictor of death [adjusted odds ratio (aOR) 7.86]. Other significant mortality risk factors included presentation with miliary TB (aOR 4.10; 95% confidence interval: 2.14-7.88), ≥35 years of age (aOR 3.04), non-Han ethnicity (aOR 1.67), and farming as an occupation (aOR 1.59). For patients with TB/HIV co-infection, miliary TB was the strongest risk factor for death (aOR 5.48). A low CD4 count (≤200 cells/μL) (aOR 3.27) at the time of TB treatment initiation and a lack of antiretroviral therapy (ART) administration (aOR 3.78) were also correlated with an increased risk of death.
Conclusion Infection with HIV was independently associated with increased mortality during TB treatment. Offering HIV testing at the time of diagnosis with TB, early TB diagnosis among HIV/acquired immunodeficiency syndrome patients, and the timely provision of ART were identified as the key approaches that could reduce the number of HIV-associated TB deaths.     

Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy.

CONTEXT: Current recommendations for initiation of antiretroviral therapy in patients infected with human immunodeficiency virus type 1 (HIV) are based on CD4 T-lymphocyte cell counts and plasma HIV RNA levels. The relative prognostic value of each marker following initiation of therapy has not been fully characterized. OBJECTIVE: To describe rates of disease progression to death and AIDS or death among patients starting triple-drug antiretroviral therapy, stratified by baseline CD4 cell count and HIV RNA levels. DESIGN, SETTING, AND PARTICIPANTS: Population-based analysis of 1219 antiretroviral therapy-naive HIV-positive men and women aged 18 years or older in British Columbia who initiated triple-drug therapy between August 1, 1996, and September 30, 1999. MAIN OUTCOME MEASURE: Cumulative mortality rates from the initiation of triple-drug antiretroviral therapy to September 30, 2000, determined using various CD4 cell and plasma HIV RNA thresholds. RESULTS: As of September 30, 2000, 82 patients had died of AIDS-related causes, for a crude AIDS-related mortality rate of 6.7%. The product limit estimate (SE) of the cumulative mortality rate at 12 months was 2.9% (0.5%). In univariate analyses, a prior diagnosis of acquired immunodeficiency syndrome (AIDS), CD4 cell count, use of protease inhibitors, and HIV RNA level were associated with mortality. There was no difference in mortality by age or sex. Only CD4 cell count remained statistically significant in the multivariate analysis. After controlling for AIDS, protease inhibitor use, and plasma HIV RNA level at baseline, patients with CD4 cell counts of less than 50/microL were 6.67 (95% confidence interval [CI], 3.61-12.34) times and those with counts of 50/microL to 199/microL were 3.41 (95% CI, 1.93-6.03) times more likely to die than those with counts of at least 200/microL. CONCLUSION: Our data demonstrate uniformly low rates of disease progression to death and AIDS or death among patients starting antiretroviral therapy with CD4 cell counts of at least 200/microL. In our study, disease progression to death and AIDS or death was clustered among patients starting therapy with CD4 cell counts less than 200/microL.     

Antiretroviral therapy: Shifting sands

HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV.     

我国免费艾滋病抗病毒治疗策略与“治疗即预防”进展情况

本文通过对比我国多年免费艾滋病抗病毒治疗的相关研究,阐述了自2003年始,我国免费艾滋病抗病毒治疗策略的调整和取得成效：随着治疗标准、用药方案和治疗点管理模式等的调整以及艾滋病患者社会人口学特征变化,艾滋病抗病毒治疗的效果不断提高,患者的死亡率显著降低,预期寿命不断提高,HIV耐药率也得到有效的控制;“治疗即预防”是减少HIV新发感染的最有效措施之一,在公共卫生层面早期开展抗病毒治疗可以有效降低HIV的传播。同时指出,随着免费艾滋病抗病毒治疗标准的降低,接受免费抗病毒治疗的患者服药依从性降低,脱失比例升高,病毒抑制率较理论值偏低等,这些是制约我国“治疗即预防”效果的关键因素。     

Prevention and control of HIV/AIDS in China: lessons from the past three decades

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.     

提高HIV/AIDS抗病毒治疗依从性的理论模型研究

通过对治疗相关依从性的回顾性研究,在界定HIV/AIDS抗病毒治疗依从性概念的基础上,分析依从性对治疗艾滋病的重要性和意义,从病人、疾病、治疗、医患关系、环境等方面探讨影响HIV/AIDS抗病毒治疗依从性的因素,构建由医疗机构、家庭、社区组织提供支持的提高依从性的理论模型。     

艾滋病25年回顾:机遇与挑战

自1981年美国报道首例艾滋病患者到目前有效的抗艾滋病病毒治疗的不断发展,25年中人类对艾滋病的研究已取得举世瞩目的成就。此外,在艾滋病的流行病学、病毒学、免疫学、致病机制和检测方法方面,也有多项突破性进展。近年,中国艾滋病相关研究发展迅速,并取得了很大进步。     

四川省西昌市2008—2018年初始抗病毒治疗HIV感染者死亡和脱失情况

目的 了解四川省西昌市2008–2018年初始抗病毒治疗HIV感染者死亡和脱失的情况及其影响因素。方法 采用回顾性队列研究的方法,从艾滋病基本防治信息系统选取2008–2018年在西昌市首次开始抗病毒治疗（ART）的HIV感染者,分析抗病毒治疗者的死亡和脱失情况。采用Cox比例风险回归模型对影响抗病毒治疗HIV感染者病死率和脱失率的相关因素进行分析。结果 共计2 723例HIV感染者进入队列,总体病死率为1.92/100人年,总体脱失率为2.49/100人年。在开始抗病毒治疗的第1年内病死率和脱失率分别为10.83/100人年、13.89/100人年。Cox回归分析结果显示接受抗病毒治疗患者主要的死亡风险是年龄≥40岁（HR=2.30,95%CI：1.53~3.48）、男性（HR=1.94,95%CI：1.14~3.30）、ART前一年内结核感染（HR=1.92,95%CI：1.01~3.65）、ART前三个月出现艾滋病相关疾病/症状（HR=2.44,95%CI：1.50~3.99）、ART前乙肝感染（HR=2.50,95%CI：1.32~4.71）、CD4⁺T淋巴细胞计数< 200 cells/ul（HR=1.79,95%CI：1.12~2.86）。接受抗病毒治疗患者主要的脱失风险是年龄≥40岁（HR=1.53,95%CI：1.07~2.18）、男性（HR=5.60,95%CI：2.60~12.08）、静脉吸毒（HR=2.18,95%CI：1.46~3.27）、初始抗病毒治疗方案为EFV+3TC+TDF（HR=2.57,95%CI：1.32~5.01）。结论 西昌市HIV感染者的抗病毒治疗效果显著,但在开始治疗的第1年内病死率和脱失率较高。抗病毒治疗工作需采取针对性的措施,重点要减少静脉吸毒人群刑满释放后的脱失,从而提高抗病毒治疗效果。     

Overview of antiretroviral treatment in China: advancement and challenges

As the severity of the HIV epidemic in China grew, National Free Antiretroviral Treatment (ART) Program was announced since 2003. Even though there still were many difficulties, China had obtained great achievements in fighting against HIV. Over 52 000 adult patients had received first-line HAART thus far and the mortality of AIDS in China decreased significantly. This paper presents an overview of the HIV/AIDS epidemic in China; the status of national free ART program, the difficulties suffered and the achievements made since the initiation of program and the challenges ahead for continued progress for China. This paper also provides suggestions to overcome these challenges.

     

Immune reconstitution inflammatory syndrome: immune restoration disease 20 years on

Restoration of immune responses against opportunistic pathogens after commencing antiretroviral therapy (ART) may cause immune restoration disease (IRD) in about 10%-40% of HIV patients with low CD4(+) T-cell counts and usually presents clinically as a type of immune reconstitution inflammatory syndrome (IRIS). IRIS may be associated with many different opportunistic pathogens, but types associated with Mycobacterium tuberculosis, BCG, cryptococci, JC polyomavirus (the cause of progressive multifocal leukoencephalopathy [PML]), hepatitis C virus and hepatitis B virus infection are the most informative about disease pathogenesis and management. A CD4(+) T-cell count of < 50/μL and a high pathogen load are the most commonly identified risk factors for IRIS. Recovery of pathogen-specific T-cell responses and perturbations of innate immune responses before and after ART appear to cause immunopathological abnormality in tissues infected by the pathogen. Prevention of IRIS may be influenced by the timing of ART: The risk of tuberculosis (TB)-associated-IRIS can be reduced by commencing ART after 8 weeks of TB treatment, but rates of AIDS or death are lower if ART is commenced during the first 4 weeks of TB treatment. Outcomes for patients with HIV and treated cryptococcal or TB meningitis may be improved by deferring ART until the opportunistic infection is fully suppressed, but data are inadequate. As ART is currently the only effective treatment for PML in patients with HIV, PML-associated IRIS cannot be prevented by manipulating the timing of ART. A greater understanding of the immunopathogenesis of IRIS may lead to targeted therapies.     

Drug Resistance to HIV-1 Integrase Inhibitors among Treatment-naive Patients in Jiangsu,China

Integrase strand transfer inhibitors (InSTIs) have been widely used in recent years because of their high genetic barrier to resistance. The World Health Organization (WHO) has recommended dolutegravir (DTG)-containing regimens as the preferred first- and second-line antiretroviral therapy (ART) regimens for people living with human immunodeficiency virus (HIV)[1]. During the long-term treatment process, the appearance of drug resistance mutations to InSTIs is inevitable. A meta-analysis has shown that the resistance rate among InSTI treatment-experienced patients is 3.9％ (Raltegravir, RAL), 1.2％ (Elvitegravir, EVG), and 0.1％ (DTG)[2]. However, resistance to InSTIs has not been reported in treatment-naive populations.     

Analysis of resistance testing in South Trinidad

The introduction of antiretroviral therapy in Trinidad and Tobago in the 1980s has resulted in a decrease in mortality of HIV-infected persons. Poor adherence to antiretroviral therapy (ART) has resulted in the development of multidrug resistant HIV Resistance testing done on 40 samples showed that 64.8% of patients had K103 mutation, 75.6% of patients had M184 mutations and 62% of patients showed resistance to tenofovir suggesting that the K65R mutation was highly likely to be present. There was reduced activity to the protease inhibitors; no resistance was found to the protease inhibitor, darunavir. Thus, there is a need for salvage therapy to be introduced which will result in virologic suppression and potentially stop the spread of multidrug resistant HIV Darunavir a new generation protease inhibitor, is an essential part of salvage therapy and needs to be introduced into the national formulary.     

人类免疫缺陷病毒感染早期启动抗逆转录病毒治疗的意义

人类免疫缺陷病毒（HIV）感染者如在感染早期未及时诊断和治疗,HIV将在体内持续复制,损害免疫系统。目前,越来越多的指南建议HIV感染者应尽早启动抗逆转录病毒治疗（ART）,尤其是急性HIV感染者。早发现并在感染早期开始ART可以限制病毒储存库的规模,改善免疫细胞功能。从社会层面而言,感染早期的患者通过启动ART达到病毒抑制状态,可以减少HIV的传播机会,降低获得性免疫缺陷综合征（AIDS）的发病率,进而减少与AIDS相关的卫生支出。但HIV感染早期诊断及治疗存在个人因素和社会因素等方面的问题,阻碍了早期治疗的实施和开展。尽早启动ART,联合其他治疗策略,有可能真正实现功能性治愈。     

云南省某地艾滋病抗病毒治疗脱失患者的调查

目的 调查云南省某地某地接受免费艾滋病抗病毒治疗患者脱失原因及其影响因素.方法 整理云南省某地2004年7月至2015年5月的艾滋病抗病毒治疗患者资料, 采用χ2检验, Logistic回归分析患者治疗过程中出现脱失的可能影响因素.结果 6 614例接受抗病毒治疗的艾滋病患者中, 540例患者由于各种原因在抗病毒治疗过程中脱失, 脱失率8.2%.艾滋病抗病毒治疗过程中脱失的主要类型为失访 (402例, 74.4%) , 停药 (138例, 25.6%) .婚姻状况为已婚或同居、通过静脉吸毒感染、入组治疗基线CD4细胞计数>500个/μL、接受治疗时间小于6个月等均增加患者治疗过程中脱失概率.结论 在艾滋病抗病毒治疗过程中应加强对吸毒人群、未婚/离异、CD4细胞计数>500个/μL和治疗时间在6月内人群应给予重视, 加强患者依从性教育和关怀, 减少脱失.     

广东省艾滋病免费抗病毒治疗维持状况调查

目的：调查广东省艾滋病免费抗病毒治疗的维持状况,探讨影响病人治疗维持时间的因素。方法：利用国家统一的成人DataFax抗病毒治疗信息数据库,收集全省1307名接受抗病毒治疗病人的资料,采用COX比例风险模型,对影响抗病毒治疗的维持时间之因素进行分析。结果：2004年10月至2008年5月全省共免费治疗1307名病人,其中66．7％病人在出现艾滋病相关症状后才被检测出HIV阳性;52．3％开始治疗时已经进入临床Ⅲ期;29．9％进入了临床Ⅳ期。88．2％的人开始治疗时CD4^＋T细胞低于200个／μL;结束治疗病人中,88．9％维持治疗时间小于1年,维持治疗时间最长的达到3年,影响病人维持治疗时间的主要因素是漏服次数、更换方案次数、治疗开始时CD4^＋T细胞水平、静脉吸毒感染。结论：应采取措施尽量延长病人治疗时间,加强对患者特别是静脉吸毒者的服药依从性教育,及时监测病人的服药情况,必要时及时调整方案。     

Predictors of first line antiretroviral therapy failure and burden of second line antiretroviral therapy

BackgroundAs HIV steps into the third decade, there are more number of patients living on lifelong (antiretroviral therapy) ART and facing the threat of drug resistance with subsequent treatment failure. The aim of this study was to determine predictors of first-line ART failure with the objectives to estimate the burden of 2nd line ART.MethodsA retrospective 5-year cohort of HIV patients who were initiated on first line ART in 2008–09 was studied. Patients were followed from the time of ART initiation. Kaplan–Meier methods and Cox proportional hazards regression models were used to estimate probabilities and predictors of first line ART failure.ResultsOf the total of 195 patients initiated on first line ART, 15 patients were switched to second line ART yielding 7.69% failure rate. During the 7178 person-years of follow-up, the incidence of first line ART failure was 2.09 per 1000 person-years. The Kaplan–Meier survival analysis gave a mean survival time of 55.6 months. BMI, CD4 count at ART initiation and presence of opportunistic infections were significant predictors of first line ART failure. The burden of second line ART patients by the end of 5 years of first line ART is expected to be 151 patients.ConclusionThough the first line ART failure is quite low in this study, we still need to be vigilant for lower BMI, low baseline CD4 count and occurrence of opportunistic infections to efficiently manage failures on first line ART.     

HIV Testing and Antiretroviral Therapy in Government and Mission Hospitals in Malawi: 2002 – 2007

HIV testing and antiretroviral therapy (ART) has scaled up tremendously in Malawi in the last 5 years. We analyzed trends of HIV testing uptake in the course of ART scale-up in 25 government and mission hospitals, which were selected because they do not receive support from non-governmental organizations. Data on numbers of clients HIV tested and on cumulative ART registrations were collected from annual country-wide situational analyses and from quarterly ART supervisory visits from 2002 to 2007. In the period before ART scale up, the quarterly number of clients HIV tested increased from 2609 in 2002 to 8197 in 2004, equivalent to an average quarterly increase of 559 tests. During ART scale up, the quarterly number of clients HIV tested increased from 17977 in early 2005 to 35344 in the second quarter of 2007, equivalent to an average quarterly increase of 2171 tests. During this time, the cumulative number of patients started on ART increased from 2441 to 29756. There has been a rapid acceleration of HIV testing uptake and ART in government and mission hospitals. ART may facilitate the decision of clients to have an HIV test and therefore contribute in this way to HIV prevention efforts.