Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

The Enigma of the Human Immunodeficiency Virus (HIV) Epidemic in China.

Nearly 17 years ago China launched its National HIV/AIDS Response Program, yet the epidemic still is not slowing. New cases and new deaths increase every year-in 2005, 40 711 people living with human immunodeficiency virus (HIV; PLWH) were diagnosed and 5729 died, whereas in 2019, 148 598 PLWH were diagnosed and 31 522 died. Moreover, the estimated PLWH population in China has risen to >1.25 million. However, epidemic data are worryingly complex and difficult to interpret, presenting challenges to the redirection and refocusing of efforts toward achievement of control. Here we present three "windows" into China's epidemic data. From these viewpoints, it appears we still do not know how much infection exists, how much transmission is occurring, and in what contexts transmission happens. The enigma that is China's HIV epidemic must be better understood. A new research agenda must be developed and executed if we are to change the future of HIV in China.

One Hundred Days of Coronavirus Disease 2019 Prevention and Control in China.

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China's response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.

Nationwide Cohort Study of Antiretroviral Therapy Timing: Treatment Dropout and Virological Failure in China, 2011-2015.

Background: People living with human immunodeficiency virus (PLWH) are still being diagnosed late, rendering the benefits of "early" antiretroviral therapy (ART) unattainable. Therefore, we aimed to evaluate the benefits of "immediate" ART. Methods: A nationwide cohort of PLWH in China who initiated ART January 1, 2011, to December 31, 2014 and had baseline CD4 results >200 cells/µL were censored at 12 months, dropout, or death, whichever came first. Treatment dropout and virological failure (viral load ≥400 copies/mL) were measured. Determinants were assessed by Cox and log-binomial regression. Results: The cohort included 123605 PLWH. The ≤30 days group had a significantly lower treatment dropout rate of 6.72%, compared to 8.91% for the 91-365 days group and to 12.64% for the >365 days group. The ≤30 days group also had a significantly lower virological failure rate of 5.45% (31-90 days: 7.39%; 91-365 days: 9.64%; >365 days: 12.67%). Greater risk of dropout (91-365 days: adjusted hazard ratio [aHR] = 1.33, 95% confidence interval [CI] = 1.25-1.42; >365 days: aHR = 1.55, CI = 1.47-1.54), and virological failure (31-90 days: adjusted risk ratio [aRR] = 1.35, CI = 1.26-1.45; 91-365 days: aRR = 1.66, CI = 1.55-1.78; >365 days: aRR = 1.85, CI = 1.74-1.97) were observed for those who delayed treatment. Conclusions: ART within 30 days of HIV diagnosis was associated with significantly reduced risk of treatment failure, highlighting the need to implement test-and-immediately-treat policies.

History of the HIV Epidemic in China.

PURPOSE OF REVIEW: This study aims to review the history of the human immunodeficiency virus (HIV) infection epidemic in China. RECENT FINDINGS: The HIV infection epidemic in China has evolved significantly over the past 35 years, from initially exclusively within people who inject drugs (PWID), to outbreaks due to plasma collection contamination in the mid-1990s, to now almost exclusive transmission via sexual contact. The number of newly-diagnosed cases and the number HIV-related deaths have increased each year since 2004, coinciding with a massive scale-up of both HIV testing and antiretroviral therapy initiation. The proportion of cases diagnosed later in their disease progression has remained constant. The initial outbreaks of HIV across China were identified quickly and the overall trends have been monitored. While the HIV epidemic among PWID has been well managed, the growing HIV epidemic via sexual contact has grown more complex and even more difficult to control.

Immediate Antiretroviral Therapy Decreases Mortality Among Patients With High CD4 Counts in China: A Nationwide, Retrospective Cohort Study.

Background: Clinical trials have demonstrated that immediate initiation of antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality. We tested the hypothesis that initiating ART ≤30 days after human immunodeficiency virus (HIV) diagnosis would be associated with reduced mortality among people living with HIV (PLWH) with CD4 counts >500 cells/µL. Methods: PLWH enrolled in the Chinese National HIV Information System between January 2012 and June 2014 with CD4 counts >500 cells/µL were followed for 12 months. Cox proportional hazards model was used to determine hazard ratios (HRs) for PLWH who initiated ART after HIV diagnosis. ART initiation was treated as a time-dependent variable. Results: We enrolled 34581 PLWH with CD4 >500 cells/µL; 1838 (5.3%) initiated ART ≤30 days after diagnosis (immediate ART group), and 19 deaths were observed with a mortality rate of 1.04 per 100 person-years (PY). Fifty-eight deaths were documented among the 5640 PLWH in the delayed ART group with a mortality rate of 2.25 per 100 PY. There were 713 deaths among the 27103 PLWH in the no ART group with a mortality rate of 2.39 per 100 PY. After controlling for potential confounding factors, ART initiation at ≤30 days (adjusted HR, 0.37 [95% confidence interval, .23-.58]) was a statistically significant protective factor. Conclusions: We found that immediate ART is associated with a 63% reduction in overall mortality among PLWH with CD4 counts >500 cells/µL in China, supporting the recommendation to initiate ART immediately following HIV diagnosis.

The Human Immunodeficiency Virus Care Continuum in China: 1985-2015.

Background: Human immunodeficiency virus (HIV) care continuum attrition is a major global public health challenge. Few studies have examined this problem in resource-limited settings. We aimed to assess cumulative, current, and historical achievement along China's HIV continuum of care. Methods: A nationwide, serial cross-sectional study of all individuals with HIV infection diagnosed in China between 1 January 1985 and 31 December 2015 was conducted using data from China's HIV/AIDS information systems. Biennial estimates of the number of persons living with HIV were also used. We defined 7 steps in HIV care continuum as infected (estimated), diagnosed, linked, retained, enrolled, receiving antiretroviral therapy (ART), and virally suppressed. Cumulative, 30-year performance, and biennial performance during the most recent 10 years were examined. Results: A total of 573529 persons diagnosed with HIV infection were included. Cumulatively, 94% were linked, 88% were retained, 73% were enrolled, 67% were receiving ART, and 44% were suppressed. Greatest attrition was observed for adolescents, minorities, and those who reported injecting drug use as their route of infection. Improvement was observed from 2005 to 2015. As of the end of 2015, 68% among those infected were diagnosed, 67% among diagnosed were receiving ART, and 65% among those receiving ART were virally suppressed. After adjusting for those without viral load testing, the proportion suppressed increased to 89%. Conclusions: Despite dramatic improvements, China faces serious challenges in achieving the Joint United Nations Programme on HIV/AIDS 90-90-90 targets, because of substantial attrition along its continuum of HIV care.

Care cascade structural intervention versus standard of care in the diagnosis and treatment of HIV in China: a cluster-randomized controlled trial protocol.

BACKGROUND: The high rate of attrition along the care cascade of infection with human immunodeficiency virus (HIV) results in lost opportunities to provide timely antiretroviral therapy (ART) and to prevent unnecessarily high mortality. This study aims to assess the effectiveness of a structural intervention, the one-stop ("One4All") strategy that streamlines China's HIV care cascade with the intent to improve testing completeness, ART initiation, viral suppression, and mortality. METHOD: A two-arm, cluster-randomized controlled trial was implemented in twelve county hospitals in Guangxi China to test the effectiveness of the One4All strategy (intervention arm) compared to the current standard of care (SOC; control arm). The twelve study hospitals were selected for homogeneity and allocated one-to-one to the intervention and control arms. All patients screening HIV positive in study hospitals were enrolled. Target study enrollment was 180 participants per arm, 30 participants per hospital. Basic demographic information was collected as well as HIV risk behavior and route of infection. In intervention hospitals, patients then went on to receive point-of-care CD4 testing and in-parallel viral load (VL) testing whereas patients in control hospitals progressed through the usual SOC cascade. The primary outcome measure was testing completeness within 30 days of positive initial HIV screening result. Testing completeness was defined as receipt of all tests, test results, and post-test counseling. The secondary outcome measure was ART initiation (receipt of first ART prescriptions) within 90 days of positive initial HIV screening result. Tertiary outcome measures were viral suppression (≤200 copies/mL) and all-cause mortality at 12 months. DISCUSSION: We expect that this first-ever, cluster-randomized controlled trial of a bundle of interventions intended to streamline the HIV care cascade in China (the One4All strategy) will provide strong evidence for the benefit of accelerating diagnosis, thorough clinical assessment, and ART initiation via an optimized HIV care cascade. We furthermore anticipate that this evidence will be valuable to policymakers looking to elevate China's overall HIV/AIDS response to meet the UNAIDS 90-90-90 targets and the broader, global goal of eradication of the HIV/AIDS epidemic. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02084316 . (Registered on March 7, 2014).

Factors associated with mortality of HIV-positive clients receiving methadone maintenance treatment in China.

BACKGROUND: Little is known about mortality of opiate users attending methadone maintenance treatment (MMT) clinics. We sought to investigate mortality and its predictors among human immunodeficiency virus (HIV)-positive MMT clients. METHODS: Records of 306 786 clients enrolled in China's MMT program from 24 March 2004 to 30 April 2011 were abstracted. Mortality rates were calculated for all HIV-positive antiretroviral treatment (ART)-naive and ART-experienced clients. Risk factors were examined using stratified proportional hazard ratios (HRs). RESULTS: The observed mortality rate for all clients was 11.8/1000 person-years (PY, 95% confidence interval [CI], 11.5-12.1) and 57.2/1000 PY (CI, 54.9-59.4) for HIV-positive clients (n = 18 193). An increase in average methadone doses to >75 mg/day was associated with a 24% reduction in mortality (HR = 0.76, CI, .70-.82), a 48% reduction for ART-naive HIV-positive clients (HR = 0.52, CI, .42-.65), and a 47% reduction for ART-experienced HIV-positive clients (HR = 0.53, CI, .46-.62). Among ART-experienced clients, initiation of ART when the CD4(+) T-cell count was >300 cells/mm(3) (HR = 0.64, CI, .43-.94) was also associated with decreased risk of death. CONCLUSIONS: We found high mortality rates among HIV-positive MMT clients, yet decreased risk of death, with earlier ART initiation and higher methadone doses. A higher daily methadone dose was associated with reduced mortality in both HIV-infected and HIV-uninfected clients, independent of ART.

Mortality and treatment outcomes of China's National Pediatric antiretroviral therapy program.

BACKGROUND: The aim of this study was to describe 3-year mortality rates, associated risk factors, and long-term clinical outcomes of children enrolled in China's national free pediatric antiretroviral therapy (ART) program. METHODS: Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS case reporting and national pediatric ART databases for all HIV-positive children ≤15 years old who initiated ART prior to December 2010. Mortality risk factors over 3 years of follow-up were examined using Cox proportional hazards regression models. Life tables were used to determine survival rate over time. Longitudinal plots of CD4(+) T-cell percentage (CD4%), hemoglobin level, weight-for-age z (WAZ) score, and height-for-age z (HAZ) score were created using generalized estimating equation models. RESULTS: Among the 1818 children included in our cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75-2.78). The strongest factor associated with mortality was baseline WAZ score <-2 (adjusted hazard ratio [HR] = 9.1; 95% CI, 2.5-33.2), followed by World Health Organization stage III or IV disease (adjusted HR = 2.4; 95% CI, 1.1-5.2), and hemoglobin <90 g/L (adjusted HR = 2.2; 95% CI, 1.2-3.9). CD4%, hemoglobin level, WAZ score, and HAZ score increased over time. CONCLUSIONS: Our finding that 94% of children engaged in this program are still alive and of improved health after 3 years of treatment demonstrates that China's national pediatric ART program is effective. This program needs to be expanded to better meet treatment demands, and efforts to identify HIV-positive children earlier must be prioritized.

HIV and syphilis prevalence among men who have sex with men: a cross-sectional survey of 61 cities in China.

BACKGROUND: Human immunodeficiency virus (HIV) has rapidly spread among men who have sex with men (MSM) in China in recent years; the magnitude of the epidemic is unclear. We sought to test 3 hypotheses: (1) The prevalence of both HIV and syphilis among MSM in China is high, (2) the 2 epidemics each have unique geographical distributions, and (3) demographic and sexual behavior characteristics are different among segments of the MSM population in China. METHODS: A total of 47 231 MSM from 61 cities in China participated in a cross-sectional survey conducted from February 2008 to September 2009. Demographic and behavioral data were collected and analyzed and blood samples tested for HIV and syphilis. Three subgroups among the broader MSM sample were described. Main outcome measures were HIV and syphilis prevalence. RESULTS: An overall prevalence of 4.9% (2314/47 231; 95% confidence interval [CI], 4.7%-5.1%) for HIV and 11.8% (5552/47 231; 95% CI, 11.5%-12.0%) for syphilis was found. Syphilis-positive MSM had the highest HIV prevalence, 12.5% (693/5552; 95% CI, 11.6%-13.4%). However, correlations between HIV and syphilis prevalence were found in only 3 of 6 geographical regions (Northwest: r = 0.82, P = .0253; East: r = 0.78, P = .0004; and South-central: r = 0.63, P = .0276). Three subgroups-nonlocal MSM, Internet-using MSM, and female-partnering MSM-were found to have different profiles of characteristics and behaviors. CONCLUSIONS: HIV and syphilis prevalences among MSM in China are high and the 2 epidemics are largely separate geographically. Three segments of the Chinese MSM population each have different demographic and sexual risk "profiles" that suggest high potential for bridging infection across geographies, generations, and sexes.

Methadone maintenance treatment and mortality in HIV-positive people who inject opioids in China.

OBJECTIVE: To examine the effect of methadone maintenance treatment (MMT) on mortality in people injecting opioids who receive antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection in China. METHODS: The study involved a nationwide cohort of 23 813 HIV-positive (HIV+) people injecting opioids who received ART between 31 December 2002 and 31 December 2011. Mortality rates and demographic, disease and treatment characteristics were compared in patients who received either ART and MMT or ART only. Factors associated with mortality were identified by univariate and multivariate analysis. FINDINGS: Overall, 3057 deaths occurred during 41 959 person-years of follow-up (mortality: 7.3 per 100 person-years; 95% confidence interval, CI: 7.0-7.5). Mortality 6 months after starting ART was significantly lower with ART and MMT than with ART only (6.6 versus 16.9 per 100 person-years, respectively; P < 0.001). After 12 months, mortality was 3.7 and 7.4 per 100 person-years in the two groups, respectively (P < 0.001). Not having received MMT was an independent predictor of death (adjusted hazard ratio: 1.4; 95% CI: 1.3-1.6). Other predictors were a low haemoglobin level and a low CD4+ T-lymphocyte count at ART initiation and treatment at facilities other than infectious disease hospitals. CONCLUSION: Patients would benefit more from both MMT and HIV treatment programmes and would face fewer barriers to care if cross-referrals between programmes were promoted and ART and MMT services were located together.

Human resource development and capacity-building during China's rapid scale-up of methadone maintenance treatment services.

PROBLEM: China's National Methadone Maintenance Treatment Programme (MMT) has expanded from eight clinics serving approximately 1000 clients to 738 clinics that have served more than 340 000 clients cumulatively in only 8 years. This has created an enormous demand for trained providers. APPROACH: Human resource development and capacity building efforts have been conducted in China's National MMT Programme to create a supply of providers trained in administering MMT for opioid dependence. LOCAL SETTING: From 2004 to 2007, China's National MMT Programme faced several problems: inappropriately low methadone doses, poor compliance, high concurrent drug use and high drop-out rates among clients, and little experience, little training and high turnover rates among providers. RELEVANT CHANGES: Training programmes for individual providers and their trainers were redeveloped and expanded in 2008. Although programme performance metrics show an increase in patients' annual mean duration in treatment (93 days in 2004 versus 238 days in 2011), the increase in their mean daily methadone dose (from 47.2 mg in 2004 to 58.6 mg in 2011) is modest. LESSONS LEARNT: Some of the problems that can arise during the development, launch and scale-up of a major national public health effort, such as China's National MMT Programme, cannot be foreseen. Key to the programme's success so far have been the strong commitment on the part of China's government and the optimism and pragmatism of programme managers. Human resources development and capacity-building during scale-up have contributed to improved service quality in MMT treatment clinics and are critical to long-term success.

Referring heroin users from compulsory detoxification centers to community methadone maintenance treatment: a comparison of three models.

BACKGROUND: Both compulsory detoxification treatment and community-based methadone maintenance treatment (MMT) exist for heroin addicts in China. We aim to examine the effectiveness of three intervention models for referring heroin addicts released from compulsory detoxification centers to community methadone maintenance treatment (MMT) clinics in Dehong prefecture, Yunnan province, China. METHODS: Using a quasi-experimental study design, three different referral models were assigned to four detoxification centers. Heroin addicts were enrolled based on their fulfillment to eligibility criteria and provision of informed consent. Two months prior to their release, information on demographic characteristics, history of heroin use, and prior participation in intervention programs was collected via a survey, and blood samples were obtained for HIV testing. All subjects were followed for six months after release from detoxification centers. Multi-level logistic regression analysis was used to examine factors predicting successful referrals to MMT clinics. RESULTS: Of the 226 participants who were released and followed, 9.7% were successfully referred to MMT(16.2% of HIV-positive participants and 7.0% of HIV-negative participants). A higher proportion of successful referrals was observed among participants who received both referral cards and MMT treatment while still in detoxification centers (25.8%) as compared to those who received both referral cards and police-assisted MMT enrollment (5.4%) and those who received referral cards only (0%). Furthermore, those who received referral cards and MMT treatment while still in detoxification had increased odds of successful referral to an MMT clinic (adjusted OR = 1.2, CI = 1.1-1.3). Having participated in an MMT program prior to detention (OR = 1.5, CI = 1.3-1.6) was the only baseline covariate associated with increased odds of successful referral. CONCLUSION: Findings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.

Human immunodeficiency virus/acquired immunodeficiency syndrome prevalence, incidence, and mortality in China, 1990 to 2017: a secondary analysis of the Global Burden of Disease Study 2017 data.

BACKGROUND: Despite almost two decades of well-funded and comprehensive response efforts by the Chinese Government, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) remains a major problem in China. Yet, few studies have recently examined long-term trends in HIV/AIDS prevalence, incidence, and mortality at the national level. This study aimed to determine the prevalence, incidence, and mortality trends for HIV/AIDS over the past 28 years in China. METHODS: We conducted a descriptive, epidemiological, secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data. To evaluate trends in prevalence, incidence, and mortality over the study period from 1990 to 2017, we calculated values for annual percentage change (APC) and corresponding 95% confidence intervals (CIs) using joinpoint regression analysis. RESULTS: A significant increase in HIV/AIDS prevalence was observed for 1990 to 2009 (APC: 10.7; 95% CI: 10.4, 11.0; P < 0.001), and then remained stable for 2009 to 2017 (APC: 0.7; 95% CI: -0.3, 1.7; P = 0.1). A significant increase in HIV incidence was also observed for 1990 to 2005 (APC: 13.0; 95% CI: 12.6, 13.4; P < 0.001), and then a significant decrease was detected for 2005 to 2017 (APC: -6.5; 95% CI: -7.0, -6.1; P < 0.001). A significant increase in AIDS-related mortality rate was detected for 1990 to 2004 (APC: 10.3; 95% CI: 9.3, 11.3; P < 0.001), followed by a period of stability for 2004 to 2013 (APC: 1.3; 95% CI: -0.7, 3.3; P = 0.2), and then another significant increase for 2013 to 2017 (APC: 15.3; 95% CI: 8.7, 22.2; P < 0.001). CONCLUSIONS: Although prevalence has stabilized and incidence has declined, AIDS-related mortality has risen sharply in recent years. These findings suggest more must be done to bring people into treatment earlier, retain them in treatment more effectively, actively seek to reenter them in treatment if they dropout, and improve the quality of treatment and care regimens.