Decai Zhao

The Chinese free antiretroviral treatment program: challenges and responses.

To respond to the HIV/AIDS epidemic in China, the National Center for AIDS/STD Control and Prevention established the Division of Treatment and Care in late 2001. The pilot for the National Free ART Program began in Henan Province in 2002, and the program fully began in 2003. Treatment efforts initially focused on patients infected through illicit blood and plasma donation in the mid-1990s and subsequently expanded to include HIV-infected injection drug users, commercial sex workers, pregnant women, and children. The National Free ART Database was established in late 2004, and includes data on current patients and those treated before 2004. Over 31 000 adult and pediatric patients have been treated thus far. Challenges for the program include integration of drug treatment services with ART, an under-resourced health care system, co-infections, stigma, discrimination, drug resistance, and procurement of second-line ART. The merging of national treatment and care, epidemiologic, and drug resistance databases will be critical for a better understanding of the epidemic, for earlier identification of patients requiring ART, and for improved patient follow-up. The Free ART Program has made considerable progress in providing the necessary care and treatment for HIV-infected people in China and has strong government support for continued improvement and expansion.

Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003–11) : a national observational cohort study

BACKGROUND On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed. METHODS In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission. FINDINGS Based on data from 38,862 serodiscordant couples, with 101,295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4-2·8) among the 14,805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per μl [IQR 314-590]) and 1·3 per 100 person-years (1·2-1·3) among the 24,057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per μl [62-269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65-0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54-0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59-0·99) or heterosexual intercourse (0·69, 0·56-0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71-1·36). INTERPRETATION Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied. FUNDING Chinese Governments 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.

Predictors of virologic failure in HIV-1-infected adults receiving first-line antiretroviral therapy in 8 provinces in China.

BACKGROUND Despite poor primary health care systems, free antiretroviral therapy (ART) has been available in China for >5 years. Virologic outcomes in Chinese patients receiving ART have not been described on a national level. METHODS A multistage cluster design was used in 8 provinces to randomly select patients who had been receiving first-line ART for at least 6 months, who were stratified into 3 treatment-duration groups. Viral load testing and patient interviews were conducted, and data were linked with national treatment database information. Collected data were analyzed for association with viral suppression by means of multivariate modeling. Adequate viral suppression was defined as a viral load of <400 copies/mL. RESULTS Of 5256 patients receiving ART, 3894 met the eligibility criteria, among whom 1153 were analyzed. Overall, 72% demonstrated viral suppression, and 82%, 73%, and 67% of the participants receiving ART for 6-11, 12-23, and > or = 24 months, respectively, experienced viral suppression (P < .001). In a multivariate model, treatment given at locations other than county-level hospitals was less likely to achieve viral suppression, with greater odds for inadequate virologic response found at village clinics (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.9-10.1), township health centers (OR, 3.1; 95% CI, 1.7-5.6), and public health clinics (OR, 3.1; 95% CI, 1.7-5.6). Patients receiving didanosine-based regimens were more likely to experience an inadequate virologic response than were those receiving lamivudine-based regimens (OR, 3.9; 95% CI, 2.7-5.7). CONCLUSIONS Chinas national ART program is largely successful at suppressing viral load. Care received outside of hospitals and regimens containing didanosine were associated with less favorable virologic outcomes.

Cohort Profile: The Chinese national free antiretroviral treatment cohort

Overall, China does not have a big HIVproblem, with only 0.05% of the total populationinfected. With 1.3 billion people, however, thisequates to an estimated 700000 infected individuals,with high rates reported among the high-risk cohortsof FPD, injection drug users, female sex workers andmen who have sex with men. Among the estimated85000 with acquired immunodeficiency syndrome(AIDS), 62838 have been reported as of October2007.

Changing baseline characteristics among patients in the China National Free Antiretroviral Treatment Program, 2002–09

Objective To improve HIV treatment in China by determining changes over time of patient characteristics (geographic, clinical and route of HIV infection) among patients enrolled in the China National Free Antiretroviral Treatment Program. Methods Patients in the national treatment database from 1 June 2002 to 1 June 2009 were eligible. Patients were excluded if <18 years old, not previously treatment-naïve, missing initial treatment date or not initiated on triple drug therapy. Results About 62 919 patients were included, located across 54.8% of counties/districts throughout mainland China; 86.4% were concentrated in 11.1% of counties/districts. Median age was 38 years, 41% female, 45.4% former plasma donors (FPDs), 33.9% sexually infected and 15.5% injection drug users (IDUs). Median baseline CD4 cell count was 129/µl. In 2002, 100% of treated were FPDs with no CD4 cell counts. By 2009, 59% of the treated were sexually infected and 96% had baseline CD4 cell counts. Injection drug users remained a minority of those treated. Conclusions Limited treatment resources can be focused on areas with more patients. Greater emphasis needs to be placed on earlier HIV diagnosis and treatment. New strategies must be identified to bring HIV-infected IDUs into treatment. Routine HIV testing would identify those at risk earlier.

Decreasing Excess Mortality of HIV-infected Patients Initiating Antiretroviral Therapy: Comparison with Mortality in General Population in China, 2003 – 2009

Objective:To evaluate excess mortality across calendar time comparing HIV-infected patients receiving combination antiretroviral therapy (cART) with the general Chinese population. Methods:Patients receiving free cART through the National Free Antiretroviral Therapy Program (NFATP) between January 1, 2003, and December 31, 2009, were included. Observed mortality rates, excess mortality rates, and standardized mortality ratios were calculated by calendar periods. Factors associated with excess mortality across calendar time were evaluated in multivariable Poisson regression models. Results:Among 64,836 HIV-infected patients, the observed and excess mortality rates in 2003–2004 were 9.5 deaths per 100 person-years [95% confidence interval (CI): 8.8 to 10.2] and 9.1 (95% CI: 8.5 to 9.8); in 2008–2009, these decreased to 5.6 (95% CI: 5.4 to 5.8) and 5.2 (95% CI: 5.0 to 5.4), respectively. The adjusted excess hazard ratio (eHR) for 2003–2004 in comparison to 2008–2009 was 1.27 (95% CI: 1.11 to 1.45). Patients initiating cART at CD4 cell counts <50 cells per microliter in comparison with ≥350 cells per microliter had an adjusted eHR of 9.92 (95% CI: 8.59 to 11.44). Patients starting cART at older ages also had greater excess mortality with an eHR of 1.63 (95% CI: 1.47 to 1.82) comparing ages ≥45 to 18–29 years. Standardized mortality ratio results were consistent with those for excess mortality. Conclusions:Substantial decreases in excess mortality were observed from 2003 to 2009 in China among HIV-infected patients receiving free cART. However, mortality among HIV-infected patients remained higher than the general Chinese population. As more efficacious first- and second-line cART regimens become increasingly available to Chinese HIV-infected patients, further reductions in overall and excess mortality are likely.

Attrition among Human Immunodeficiency Virus (HIV)- Infected Patients Initiating Antiretroviral Therapy in China, 2003–2010

Background Mortality and morbidity from HIV have dramatically decreased in both high- and low-income countries. However, some patients may not benefit from combination antiretroviral therapy (cART) because of inadequate access to HIV care, including attrition after care initiation. Methodology/Principal Findings The study population included all HIV-infected patients receiving cART through the Chinese National Free Antiretroviral Treatment Program from 1 January 2003 to 31 December 2010 (n = 106,542). We evaluated retention in HIV care and used multivariable Cox proportional hazard models to identify independent factors predictive of attrition. The cumulative probability of attrition from cART initiation was 9% at 12 months, 13% at 18 months, 16% at 24 months and 24% at 60 months. A number of factors were associated with attrition, including younger age, male gender, and being single or divorced. Patients with higher CD4 cell counts at cART initiation were more likely to drop out of HIV care. The proportion of patients remaining in HIV care increased in more recent calendar years and among patients who initiated modern cART regimens. Conclusions/Significance Retention in HIV care is essential for optimizing individual and public health outcomes. Attrition, even the degree observed in our study, can lead to premature morbidity and mortality, and possibly affect further transmission of HIV and HIV resistant drug variants. Effective strategies to promote retention in HIV care programs are needed. In China these strategies may include focusing particularly on younger male patients and those with higher CD4 cell counts at therapy initiation.

Some patient-related factors associated with late access to ART in China's free ART program

Abstract Highly active antiretroviral therapy (HAART) has become widely available in China during the past seven years. However, many patients still initiate treatment at very late stages. To understand the distribution of baseline CD4 and factors associated with late antiretroviral therapy (ART) access, the National Free ART Database was retrospectively reviewed and a total of 49,321 HIV/AIDS patients were identified in this study based on the following inclusion criteria: (1) age ≥18; (2) initiated HAART between 1 July, 2006 and 31 December, 2009; (3) have recorded baseline CD4 cell count. This study showed that although both the median and mean baseline CD4 increased consistently over the study period, there were still about 30% of HIV/AIDS patients accessing ART at a very late stage (CD4 ≤ 50 µl) in 2009. Risk factors for late ART access included being male, single, having a short time interval between HIV diagnosis and treatment, and being infected through heterosexual contact. Being infected through injection drug use and homosexual contact were protective. Transmission route and marriage status showed different effects in a gender stratified analysis. A strengthened HIV testing and screening program is the key to improving the accessibility of ART and populations that are vulnerable to sexual transmission of HIV should be the primary target of the program.

Incidence and associated factors of pulmonary tuberculosis in HIV-infected children after highly active antiretroviral therapy (HAART) in China: a retrospective study

China is a country with high tuberculosis (TB) incidence but relatively low HIV prevalence. However, due to difficulties in diagnosis and reporting, true burden of HIV-associated TB in children is unknown. The objective of this study was to describe the incidence of pulmonary TB (PTB) after antiretroviral therapy (ART) and to study risk factors. A retrospective study was performed based on routinely collected data from China national pediatric free antiretroviral treatment database. A total of 3365 children under 15 years on ART from July 2005 to October 2012 were included. Multivariable logistic regression was used to detect associated factors. Two thousand nine hundred and ninety (89%) children got infected from HIV-positive mother, with median age of 6.7 (4.1, 10.0) years at highly active antiretroviral therapy (HAART) initiation in this program. Seventy-seven (2.3%) children were diagnosed with PTB after ART during 7.3 years cohort observation. Median time of occurrence was 212 (30–514) days. Overall incidence was 0.83 (0.65–1.01)/100 person-years (py), with the peak of 3.6/100 py in the first 3 months after antiretroviral treatment. WHO stage IV at baseline showed 2 (95% CI 1.0–6.8) times more risk for developing TB. Late clinical stage at ART initiation was shown to relate with TB incidence. PTB coinfection leads to higher mortality. Early diagnosis and treatment of HIV are highly required to reduce HIV-associated morbidity and mortality due to TB.

Monitoring HIV Drug Resistance Using Early Warning Indicators in China: Results From a Pilot Survey Conducted in 2008

Robust programmatic monitoring of factors associated with the emergence of human immunodeficiency virus (HIV) drug resistance is an essential component of antiretroviral therapy (ART) program evaluation and treatment optimization. China piloted World Health Organization HIV drug resistance early warning indicators to assess the feasibility and usefulness of results. Overall, early warning indicator monitoring showed high levels of appropriate ART prescribing, low rates of loss to follow-up 12 months after ART initiation, and high rates of retention of first-line ART at 12 months. On-time drug pick-up, which may signal treatment interruptions, was identified as a challenge. HIV drug resistance early warning indicator monitoring provides a valuable assessment of ART service delivery, and its application will be scaled up throughout China.