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.

/pdf/a-comprehensive-mapping-of-hiv-1-genotypes-in-various-risk-3o5xf2j9tz.pdf

A comprehensive mapping of HIV-1 genotypes in various risk groups and regions across China based on a nationwide molecular epidemiologic survey.

This study aimed to analyse trends in notifiable infectious diseases in China, in their historical context. Both English and Chinese literature was searched and diseases were categorised according to the type of disease or transmission route. Temporal trends of morbidity and mortality rates were calculated for eight major infectious diseases types. Strong government commitment to public health responses and improvements in quality of life has led to the eradication or containment of a wide range of infectious diseases in China. The overall infectious diseases burden experienced a dramatic drop during 1975–1995, but since then, it reverted and maintained a gradual upward trend to date. Most notifiable diseases are contained at a low endemic level; however, local small-scale outbreaks remain common. Tuberculosis, as a bacterial infection, has re-emerged since the 1990s and has become prevalent in the country. Sexually transmitted infections are in a rapid, exponential growth phase, spreading from core groups to the general population. Together human immunodeficiency virus (HIV), they account for 39% of all death cases due to infectious diseases in China in 2008. Zoonotic infections, such as severe acute respiratory syndrome (SARS), rabies and influenza, pose constant threats to Chinese residents and remain the most deadly disease type among the infected individuals. Therefore, second-generation surveillance of behavioural risks or vectors associated with pathogen transmission should be scaled up. It is necessary to implement public health interventions that target HIV and relevant coinfections, address transmission associated with highly mobile populations, and reduce the risk of cross-species transmission of zoonotic pathogens.

/pdf/trends-in-notifiable-infectious-diseases-in-china-179a6epx1r.pdf

Trends in Notifiable Infectious Diseases in China: Implications for Surveillance and Population Health Policy

Abstract The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2 + γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αβ T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells. 

γδ T cells: origin and fate, subsets, diseases and immunotherapy

Human immunodeficiency virus type 1 (HIV) dysregulates γδ T cells as part of an immune evasion mechanism. Nearly 3 decades of research defined the effects of HIV on γδ T cells and how this impacts disease. With highly effective antiretroviral therapy (ART) providing virus suppression and longer survival, we expected a return to normal for γδ T cells. This is not the case. Even in patients with CD4 T cell reconstitution, normal γδ T cell levels and function are not recovered. The durable damage to Vδ2 T cells is paralleled by defects in NK, CD8 T cells and dendritic cells. Whether these consequences of HIV stem from similar or distinct mechanisms is not known and effective means for recovering the full range of cellular immunity have not been discovered. These unanswered questions receive too little attention in the overall program of efforts to cure HIV this disease. Approved drugs capable of increasing Vδ2 T cell function are being tested in clinical trials for cancer and hold promise for restoring normal function in patients with HIV disease. The impetus for conducting clinical trials will come from understanding the significance of γδ T cells in HIV disease and what might be gained from targeted immunotherapy. This review traces the history and current progress of AIDS-related research on γδ T cells. We emphasize the damage to γδ T cells that persists despite effective virus suppression. These chronic immune deficits may be linked to the comorbidities of AIDS (cancer, cardiovascular disease, metabolic disease and others) and will hinder efforts to eradicate HIV by cytotoxic T or NK cell killing. Here, we focus on one subset of T cells that may be critical in the pathogenesis of HIV and an attractive target for new immune-based therapies.

/pdf/gd-t-cells-in-hiv-disease-past-present-and-future-tj0r3d74mt.pdf

γδ T Cells in HIV Disease: Past, Present, and Future

γδ T cells, a subgroup of T cells based on the γδ TCR, when compared with conventional T cells (αβ T cells), make up a very small proportion of T cells However, its various subgroups are widely distributed in different parts of the human body and are attractive effectors for infectious disease immunity γδ T cells are activated and expanded by nonpeptidic antigens (P-Ags), major histocompatibility complex (MHC) molecules, and lipids which are associated with different kinds of pathogen infections Activation and proliferation of γδ T cells play a significant role in diverse infectious diseases induced by viruses, bacteria, and parasites and exert their potential effector function to effectively eliminate infection It is well known that many types of infectious diseases are detrimental to human life and health and give rise to high incidence of illnesses and death rate all over the world To date, there is no comprehensive understanding of the correlation between γδ T cells and infectious diseases In this review, we will focus on the various subgroups of γδ T cells (mainly Vδ1 T cells and Vδ2 T cells) which can induce multiple immune responses or effective functions to fight against common pathogen infections, such as Mycobacterium tuberculosis, Listeria monocytogenes, influenza viruses, HIV, EBV, and HBV Hopefully, the gamma-delta T cell study will provide a novel effective way to treat infectious diseases

/pdf/protective-role-of-gd-t-cells-in-different-pathogen-8qagjak1ul.pdf

Protective Role of γδ T Cells in Different Pathogen Infections and Its Potential Clinical Application.

BACKGROUND Human immunodeficiency virus (HIV) infection and disease are accompanied by decreases in the absolute number and function of Vgamma2Vdelta2 T cells, suggesting that this subset of cells may play an important role in controlling disease. We performed a cross-sectional study involving HIV-infected former blood donors and assessed the association between Vgamma2Vdelta2 T cells and markers of disease progression. METHODS Changes in Vgamma2Vdelta2 T cell count and function were compared between HIV-infected individuals and healthy blood donors using the Mann-Whitney U test. The relationships between Vgamma2Vdelta2 T cell count, plasma viral load, and CD4 T cell count were analyzed using the Spearman correlation. RESULTS We found significant positive correlations between CD4 T cell count and both total Vgamma2Vdelta2 T cell count (P<.001) and functional (isopentenyl pyrophosphate-responsive) Vgamma2Vdelta2 T cell count (P<.001). We found significant reverse correlations between viral load and both total Vgamma2Vdelta2 T cell count (P<.05) and functional Vgamma2Vdelta2 T cell count (P<.05). CONCLUSIONS The association of Vgamma2Vdelta2 T cells with disease progression in 146 HIV-infected participants supports the view that intact Vgamma2Vdelta2 T cell populations are important for controlling HIV disease.

/pdf/association-between-vg2vd2-t-cells-and-disease-progression-xysyca21xx.pdf

Association between Vγ2Vδ2 T Cells and Disease Progression after Infection with Closely Related Strains of HIV in China

BACKGROUND Unregulated commercial blood/plasma collection among farmers occurred between 1992 and 1995 in central China and caused the second major epidemic of human immunodeficiency virus type 1 (HIV-1) infection in China. It is important to characterize HIV-1-infected former blood donors and to study characteristics associated with disease progression for future clinical intervention and vaccine development. METHODS A cross-sectional study was performed on HIV-1-infected former blood donors (FBDs) and age-matched HIV-seronegative local residents. Demographic, epidemiologic, clinical and key laboratory data were collected from all study participants. Both unadjusted and adjusted multivariate linear regressions were employed to analyze the association of the decrease of CD4(+) T-cell counts with other characteristics. RESULTS Two hundred and ninety-four HIV-1-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled in this study. The unregulated blood/plasma collection occurred more than a decade (10.8 - 12.8 years) ago, which caused the rapid spread of HIV-1 infection and the high prevalence of co-infection with hepatitis C virus (HCV, 89.5%); hepatitis B virus (HBV) co-infection was observed in only 11 HIV(+)participants (3.7%). Deterioration in both clinical manifestation and laboratory parameters and increase of viral loads were observed in parallel with the decrease of CD4(+) T-cell counts. The decrease of total lymphocyte counts (P < 0.001) and hemoglobin levels (P < 0.001) and the appearance of dermatosis (P = 0.03) were observed in parallel with the decrease of CD4(+) T-cell counts whereas viral loads (P < 0.001) and CD8(+) T-cell counts (P = 0.01) were inversely associated with CD4(+) T-cell counts. CONCLUSIONS Co-infection with HCV but not HBV is highly prevalent among HIV-1-infected FBDs. CD4(+) T-cell counts is a reliable indicator for disease progression among FBDs. Total lymphocyte counts, hemoglobin level and appearance of dermatosis were positively associated with CD8(+) T-cell counts and viral loads were inversely associated with the decreased CD4(+) T-cell counts.

Epidemiology, clinical and laboratory characteristics of currently alive HIV-1 infected former blood donors naive to antiretroviral therapy in Anhui Province, China.

Several research groups have recently reported that persistent GB virus C (GBV-C) co-infected with human immunodeficiency virus (HIV) leads to slower AIDSs disease progression than HIV-1 infection alone However, these findings were not confirmed by several other studies To investigate the association between GBV-C replication and plasma HIV loads and CD4+ T cell counts, 203 HIV-1 positive former blood/plasma donors(FBDs) were enrolled from Fuyang city of Anhui Province in China Plasma specimens were collected from them and were tested for GBV-C using RT-PCR and ELISA Out of 203 specimens, 52 (256%) cases were positive for GBV-C, including 35 male (673%) and 17 female (327%) cases No significant association was identified between GBV-C infection and CD4+ T-cell counts or between GBV-C infection and HIV viral loads Since all the subjects studied were naive to ART, the influence of therapy on AIDS disease progression was ruled out in this study Overall, our data indicated that HIV-1 positive male FBDs were prone to be infected, GBV-C coinfection with HIV-1 does not significantly influence HIV/AIDS disease progression during the late stage of chronic HIV-1 infection

[Effect of GBV-C/HIV coinfection on HIV/AIDS disease progression and HIV replication].

Objective To estimate the median survival and the effect of antiretroviral therapy (ART) among HIV-positive former blood donors of Fuyang in Anhui province, China. Methods A retrospective survey was conducted among HIV-positive former blood donors, and data was collected on survivors who had received ART. Weibull function was used to calculate median survival of HIV-positive former blood donors. The effect of ART was estimated through comparing the actual number of deaths after ART with the expected number of deaths in those who did not receive ART. Results The median period of HIV infection was at the end of 1994, with the median survival of HIV-positive former blood donors in Fuyang as 10.8 years. By the end of September 2008, among 159 former blood donors, 74 received ART, with their mean CD4+ T-cell count increased from 247.8/μl to 475.1/μl (P<0.0001). 76 of the 159 former blood donors died. When comparing the expected number of deaths calculated by Weibull function, 31.7% of the total number of deaths was reduced. Conclusion Result from this study was in consistent to the UNAIDS' figures that in the absence of treatment, the net median survival time after infection with HIV was estimated to be 11 years and ART has reduced about one third of the expected deaths.

Key words: 
Human immunodeficiency virus infection;  Former blood donors;  Median survival time;  Antiretroviral therapy

[The median survival and the effect of antiretroviral therapy among HIV-positive former blood donors in Anhui province].

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Association between Vγ2Vδ2 T Cells and Disease Progression after Infection with Closely Related Strains of HIV in China

Epidemiology, clinical and laboratory characteristics of currently alive HIV-1 infected former blood donors naive to antiretroviral therapy in Anhui Province, China.

[Effect of GBV-C/HIV coinfection on HIV/AIDS disease progression and HIV replication].

[The median survival and the effect of antiretroviral therapy among HIV-positive former blood donors in Anhui province].