National Center for AIDS/STD Control and Prevention,China CDC

High quality data and effective data quality assessment are required for accurately evaluating the impact of public health interventions and measuring public health outcomes. Data, data use, and data collection process, as the three dimensions of data quality, all need to be assessed for overall data quality assessment. We reviewed current data quality assessment methods. The relevant study was identified in major databases and well-known institutional websites. We found the dimension of data was most frequently assessed. Completeness, accuracy, and timeliness were the three most-used attributes among a total of 49 attributes of data quality. The major quantitative assessment methods were descriptive surveys and data audits, whereas the common qualitative assessment methods were interview and documentation review. The limitations of the reviewed studies included inattentiveness to data use and data collection process, inconsistency in the definition of attributes of data quality, failure to address data users' concerns and a lack of systematic procedures in data quality assessment. This review study is limited by the coverage of the databases and the breadth of public health information systems. Further research could develop consistent data quality definitions and attributes. More research efforts should be given to assess the quality of data use and the quality of data collection process.

A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.

With the intense international response to the AIDS pandemic, HIV vaccines have been extensively investigated but have failed due to issues of safety or efficacy in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a rational design approach is still lacking. Nanomaterials represent an obvious opportunity in this field due to their unique physicochemical properties. Gold nanostructures are being actively studied as a promising and versatile platform for biomedical application. Herein, we report novel surface-engineered gold nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have exploited the effects of surface chemistry on the adjuvant activity of the gold nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI-modified Au NRs can significantly promote cellular and humoral immunity as well as T cell proliferation through activating antigen-presenting cells if compared to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light on the rational design of low-toxic nanomaterials as a versatile platform for vaccine nanoadjuvants/delivery systems.

Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4+ T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34+ HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdcscid/IL-2Rγnull mice. The CCR5 disruption efficiency in our system remained robust in secondary transplanted repopulating hematopoietic cells. More importantly, an HIV-1 resistance effect was observed as indicated by significant reduction of virus titration and enrichment of human CD4+ T cells. Hence, we successfully established a CRISPR/Cas9 mediated CCR5 ablating system in long-term HSCs, which confers HIV-1 resistance in vivo. Our study provides evidence for translating CCR5 gene-edited HSC transplantation for an HIV cure to the clinic. Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4+ T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34+ HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdcscid/IL-2Rγnull mice. The CCR5 disruption efficiency in our system remained robust in secondary transplanted repopulating hematopoietic cells. More importantly, an HIV-1 resistance effect was observed as indicated by significant reduction of virus titration and enrichment of human CD4+ T cells. Hence, we successfully established a CRISPR/Cas9 mediated CCR5 ablating system in long-term HSCs, which confers HIV-1 resistance in vivo. Our study provides evidence for translating CCR5 gene-edited HSC transplantation for an HIV cure to the clinic.

BACKGROUND: China is experiencing a dynamic HIV/AIDS epidemic. While serology based surveillance systems have reported the spread of HIV/AIDS, detailed tracking of its transmission in populations and regions is not possible without mapping it at the molecular level. We therefore conducted a nationwide molecular epidemiology survey across the country. METHODS: HIV-1 genotypes were determined from 1,408 HIV-positive persons newly diagnosed in 2006. The prevalence of each genotype was estimated by weighting the genotype's prevalence from each province- and risk-specific subpopulation with the number of reported cases in the corresponding subgroups in that year. RESULTS: CRF07_BC (35.5%), CRF01_AE (27.6%), CRF08_BC (20.1%), and subtype B' (9.6%) were the four main HIV-1 strains in China. CRF07_BC and CRF08_BC were the primary drivers of infection among injecting drug users in northeastern and southeastern China, respectively, and subtype B' remained dominant among former plasma donors in central China. In contrast, all four strains occurred in significant proportions among heterosexuals nationwide, pointing to an expansion of the HIV-1 epidemic from high-risk populations into the general population. CRF01_AE also replaced subtype B as the principal driver of infection among men-who-have-sex-with-men. CONCLUSIONS: Our study provides the first comprehensive baseline data on the diversity and characteristics of HIV/AIDS epidemic in China, reflecting unique region- and risk group-specific transmission dynamics. The results provide information critical for designing effective prevention measures against HIV transmission.

BACKGROUND: Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection. METHODS: We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed. RESULTS: Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (ω) of 141 days (95% CI 119-160) at normalized optical density (ODn) cutoff of 1.0, with similar ω in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections. CONCLUSIONS: These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent ω in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials.

BACKGROUND: Innovation theory has focused on the adoption of new products or services by individuals and their market-driven diffusion to the population at large. However, major health sector innovations typically emerge from negotiations between diverse stakeholders who compete to impose or at least prioritise their preferred version of that innovation. Thus, while many digital health interventions have succeeded in terms of adoption by a substantial number of providers and patients, they have generally failed to gain the level of acceptance required for their integration into national health systems that would promote sustainability and population-wide application. The area of innovation considered here relates to a growing number of success stories that have created considerable enthusiasm among donors, international agencies, and governments for the potential role of ICTs in transforming weak national health information systems in middle and low income countries. This article uses a case study approach to consider the assumptions, institutional as well as technical, underlying this enthusiasm and explores possible ways in which outcomes might be improved. METHODS: Literature review and case study analysis. RESULTS: The two systems considered have had considerable success in terms of gaining and maintaining government support and addressing the concerns of providers without compromising their core elements. In Uganda, the system has flourished in spite of severe resource constraints, using a participatory approach that has encouraged a high level of community engagement. In China, concern with past failures generated the political will to build a high quality surveillance system, using the latest technology and drawing on a highly skilled human resource base. CONCLUSIONS: Both example stress the importance of recognising the political, social and historical context within which information systems have to function. Implementers need to focus as much on the perceptions, attitudes and needs of stakeholders as on the technology. Implementers should distinguish between factors which may influence engagement at an institutional level and those aimed at supporting and supervising individuals within those institutions. Finally, we would suggest that designing interoperability into systems at the outset, rather than assuming that this can be achieved at some point in the future, may prove far easier in the longer term.

OBJECTIVES: We sought to comprehensively analyze the origin, transmission patterns and sub-epidemic clusters of the HIV-1 CRF01_AE strains in China. METHODS: Available HIV-1 CRF01_AE samples indentified in national molecular epidemiologic surveys were used to generate near full-length genome (NFLG) sequences. The new and globally available CRF01_AE NFLG sequences were subjected to phylogenetic and Bayesian molecular clock analyses, and combined with epidemiologic data to elucidate the history of CRF01_AE transmission in China. RESULTS: We generated 75 new CRF01_AE NFLG sequences from various risk populations covering all major CRF01_AE epidemic regions in China. Seven distinct phylogenetic clusters of CRF01_AE were identified. Clusters 1, 2 and 3 were prevalent among heterosexuals and IDUs in southern and southwestern provinces. Clusters 4 and 5 were found primarily among MSM in major northern cities. Clusters 6 and 7 were only detected among heterosexuals in two southeast and southwest provinces. Molecular clock analysis indicated that all CRF01_AE clusters were introduced from Southeast Asia in the 1990s, coinciding with the peak of Thailand's HIV epidemic and the initiation of China's free overseas travel policy for their citizens, which started with Thailand as the first destination country. CONCLUSION: China's HIV-1 epidemic of sexual transmissions, was initiated by multilineages of CRF01_AE strains, in contrast to the mono-lineage epidemic of B' strain in former plasma donors and IDUs. Our study underscores the difficulty in controlling HIV-1 sexual transmission compared with parenteral transmission.

Human immunodeficiency virus and hepatitis B virus exact a high toll worldwide. Both can lead to chronic disease, cancer, and death, and neither can be eradicated with the use of current therapies. Coinfection with the two viruses represents a major global health problem.

This article reviews the epidemic of HIV infection and AIDS, the Chinese national policy development in response to the epidemic, and disparities between policies and the need for AIDS prevention in China. The HIV epidemic in China has gone through three phases, and it is now at the rapid expansion phase. Since 1988, HIV/AIDS has been addressed from a legal perspective, but in the early stages laws and regulations actually hindered HIV control efforts. Since 1995 efforts have been made to improve policy decisions. Two major strategic plans were issued in 1998 and 2001, with increased government funding for implementation. Although the challenges facing HIV/AIDs control in China are many, the Chinese government is making a stronger commitment for implementing effective AIDS control measures in the country.

Stigma towards people living with HIV is pervasive in China and related to poor service utilization, psychosocial distress and diminished quality of life (QOL). In an effort to identify mechanisms to reduce HIV stigma and its negative consequences, we examined whether social support mediates the relation between enacted stigma and both depressive symptoms and QOL among 120 HIV outpatients in Beijing, China. Generally, perceived social support was associated with less stigma, less depressive symptomatology and better QOL. Using multivariable regression models, we found that social support was a full mediator of the impact of stigma on both depressive symptomatology and QOL. The findings suggest social support may be an important target of interventions to reduce the impact of stigma on poor psychosocial health outcomes.

BACKGROUND: Sporadic reports of HIV-1 infection among commercial plasma donors in China between 1994 and 1995. OBJECTIVES: (1) To determine the prevalence of HIV infection among repeat plasma donors; (2) to identify factors associated with HIV infection; and (3) to describe characteristics associated with secondary transmission. METHODS: Plasma/blood donors who had a history of donating plasma/blood before March 1, 1995, their spouses, and their children under 5 years were recruited for a cross-sectional study. A questionnaire and an HIV test were collected anonymously. Information collected included demographic characteristics, sexual behaviour, recreational drug use and history of medical care and blood/plasma donation. HIV antibody was identified by the Hema-Strip rapid test and confirmed by Western blot. The prevalence of HIV infection was calculated and risk factors associated with infection determined by univariate analyses followed by multivariate modelling. RESULTS: A total of 1517 individuals were interviewed and tested, of whom 1043 adults admitted to donating plasma. The prevalence of HIV infection among plasma donors was 12.5% and among their non-donor spouses was 2.1%. Prevalence was inversely related to educational level and was higher in married participants, but was not associated with medical care, drug abuse or multiple sexual partners. A higher frequency of plasma donation was directly associated with a higher risk of HIV infection. Multivariate analyses demonstrated that being HIV-positive was associated with being 30 to 49 years old [odds ratio (OR) = 1.9], donating both plasma and blood (OR = 2.5), and the frequency of plasma donation (OR = 14 for >10 donations per month). CONCLUSION: The study demonstrated that the prevalence of HIV infection in the commercial plasma donor population was alarmingly high. Many married individuals and those getting married in the future will transmit the virus to their spouses and future children. Plasma donors need to be alerted to the risk of being infected with HIV and of transmitting HIV to their families and others. Other countries can benefit from the experience of China in reducing the risk of HIV transmission from plasma donating.

OBJECTIVE: To present the methods used for the 2007 estimates for the number of people at risk for and infected with HIV. DESIGN: : Estimation work took place throughout 2007, led by the National Center for AIDS and Sexually Transmitted Disease Control and Prevention in collaboration with United Nations AIDS and the World Health Organization. METHODS: The workbook method was used to process prefecture and county-level surveillance data to generate HIV prevalence by risk group for each prefecture, which was in turn imported into the spectrum model to generate estimates of new infections and HIV-related deaths. RESULTS: The working group estimated that as of 2007, there were 700,000 people living with HIV/AIDS in China, with 50,000 new infections and 20,000 HIV-related deaths in that year. Injection drug use and sexual contact are still primary modes of HIV transmission, with heterosexual contact quickly becoming the dominant route, making up 44.7% of new infections in 2007. The HIV/AIDS epidemic is still highly concentrated in certain areas, with wide variation in prevalence across regions. CONCLUSIONS: The 2007 estimates are based on the most accurate and local-level data available to date, including case reports, sentinel surveillance data, results from mass screening of key target groups, and special epidemiological studies.

Fullerenol, which self-assembles into virus-sized nanoparticles, is designed as a dual-functional nanoadjuvant to generate comparable immune responses to the HIV DNA vaccine. It shows promising adjuvant activity via various immunization routes, decreasing the antigen dosage and immunization frequency while maintaining immunity levels and inducing TEM-biased immunity to combat the infection at early stage. The underlying mechanisms by which fullerenol-based formulation induces above-mentioned polyvalent immune responses are involved in activating multiple TLRs signaling pathways. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Active testing for HIV among high-risk groups in China, although controversial, is in the best interests of public health.

BACKGROUND: A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8a' that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a. METHODS: Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a. RESULTS: Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis. CONCLUSIONS: ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.

OBJECTIVES: To find and compare the levels of acceptance of and barriers to voluntary counselling and testing (VCT) among adults in two different counties of Guizhou province, China, one in which the China CARES project was operating and the other in which it was not. DESIGN: A longitudinal design with two-stage cluster sampling was employed. METHODS: A total of 1012 participants were recruited in the two counties. All participants were interviewed, then given a coupon for free VCT after the interview. Participants were paid for returning the coupon within 2 months, whether tested or not. The uptake of VCT was measured within 2 months after the interview. RESULTS: The study found that the levels of HIV/AIDS knowledge and acceptability of VCT among the adults in both counties were low. Although 459 participants (43.5%) expressed an intent to use the VCT services, only 193 (16.5%) actually visited the VCT facilities, and only 42 (3.7%) actually took an HIV test within 2 months after the interview. The use of VCT was related to occupation, age, transportation difficulties, health status, ethnicity, and high-risk behaviors. The main barriers to HIV testing included perceiving oneself as low risk, fear of unsolicited disclosure, and fear of stigma and discrimination that would result from taking the test. CONCLUSION: Education about HIV/AIDS and VCT needs to be improved, and levels of stigma and discrimination reduced, in order to enhance the uptake of VCT services, an essential step for the initiation of treatment.

In China, men who have sex with men (MSM) are at high risk for HIV. However, little is known about their HIV testing behavior. From September 2001 to January 2002, we recruited 482 men through social networks and MSM venues. We conducted HIV testing and counseling, and anonymous, standardized face-to-face interviews. Eighty-two percent of participants had never tested for HIV before the study. The most common reasons for not testing were perceived low risk of HIV infection (72%), not knowing the location of test sites (56%), fear of positive test results (54%), fear of people learning about his homosexuality (47%), and fear of breach of confidentiality about test results (47%). We identified five statistically significant independent correlates of having been tested for HIV: being older, having a college degree, being more "out" (disclosing MSM activities to people), being recruited through social networks, and having a lifetime history of sexually transmitted diseases. Of 15 participants (3.1%) who tested positive for HIV in our study, 14 (93%) did not know their status before being tested in the study. The prevalence of HIV testing among MSM in Beijing is low; almost all HIV-positive men in our study were unaware of their infection. Our findings suggest an urgent need to promote HIV testing among MSM in Beijing.

OBJECTIVE: To assess the levels of adherence to antiretroviral therapy in a sample of HIV-infected patients from rural areas in China and to determine the factors associated with suboptimal adherence. DESIGN: A cross-sectional study was conducted on HIV-infected adults receiving free antiretroviral therapy (ART) in two project sites of China's Comprehensive AIDS Response program (China CARES). METHODS: Data on socio-demographic characteristics, ART regimens, HIV/AIDS knowledge, side effects, reasons for missing doses, substance abuse, self-efficacy, doctor-patient relations and health services information was collected through face-to-face interview. The adherence rate was calculated as the number of doses taken divided by the number prescribed over the past three days. RESULTS: A total of 181 patients participated in the study and 81.8% of them reported > or = 95% adherence on the previous three days. The most frequently reported reasons for missing doses were forgetfulness, being busy and antiretroviral drug side effects. In the multivariate analysis, patients' knowledge about side effects [odds ratio (OR) = 8.08, 95% confidence interval (CI) 2.63-24.81], belief towards ART (OR = 3.20, 95% CI: 1.24-8.26), having developed reminder tools of taking medication (OR = 3.49, 95% CI: 1.36-8.96) and patient' trust and confidence in his/her doctor (OR = 7.79, 95% CI: 1.26-48.95) were independently associated with adherence. CONCLUSION: Regular ART adherence education and counseling, improved training on medication self-management skills, improved adherence monitoring and health care services should be priority strategies for improving adherence to ART among HIV/AIDS patients who receive free ART in rural China.

HIV-related stigma and discrimination are major barriers to the successful control of HIV. Stigma is associated with the disease as well as the behaviors that lead to infection. A qualitative study was conducted to identify the reasons, sources, and types of HIV-related stigma prevalent in rural China. Eighty in-depth interviews were conducted with people living with HIV/AIDS, their family members, health care providers, and uninfected villagers. Stigmatizing behaviors were primarily associated with fear of HIV rather than with the route of infection. Uninfected villagers were the main source of discrimination, with health workers and family members also holding some stigmatizing attitudes. A primary concern for HIV-positive villagers was protecting their families, especially their children, from discrimination. Secondary stigma also extended to un- infected members of the same village. The results have been used to develop an intervention to reduce fear of casual transmission and stigma in these communities.