Selective [2σ + 2σ] Cycloaddition Enabled by Boronyl Radical Catalysis: Synthesis of Highly Substituted Bicyclo[3.1.1]heptanes.

In contrast to the traditional and widely-used cycloaddition reactions involving at least a π bond component, a [2σ + 2σ] radical cycloaddition between bicyclo[1.1.0]butanes (BCBs) and cyclopropyl ketones has been developed to provide a modular, concise, and atom-economical synthetic route to substituted bicyclo[3.1.1]heptane (BCH) derivatives that are 3D bioisosteres of benzenes and core skeleton of a number of terpene natural products. The reaction was catalyzed by a combination of simple tetraalkoxydiboron(4) compound B2pin2 and 3-pentyl isonicotinate. The broad substrate scope has been demonstrated by synthesizing a series of new highly functionalized BCHs with up to six substituents on the core with up to 99% isolated yield. Computational mechanistic investigations supported a pyridine-assisted boronyl radical catalytic cycle.

Diboron(4)-Catalyzed Remote [3+2] Cycloaddition of Cyclopropanes via Dearomative/Rearomative Radical Transmission through Pyridine.

Ring structures such as pyridine, cyclopentane or their combinations are important motifs in bioactive molecules. In contrast to previous cycloaddition reactions that necessitated a directly bonded initiating functional group, this work demonstrated a novel through-(hetero)arene radical transmission concept for selective activation of a remote bond. An efficient, metal-free and atom-economical [3+2] cycloaddition between 4-pyridinyl cyclopropanes and alkenes or alkynes has been developed for modular synthesis of pyridine-substituted cyclopentanes, cyclopentenes and bicyclo[2.1.1]hexanes that are difficult to access using known methods. This complexity-building reaction was catalyzed by a very simple and inexpensive diboron(4) compound and took place via dearomative/rearomative processes. The substrate scope was broad and more than 100 new compounds were prepared in generally high yields. Mechanistic experiments and density function theory (DFT) investigation supported a radical relay catalytic cycle involving alkylidene dihydropyridine radical intermediates and boronyl radical transfer.

Catalysis with Diboron(4)/Pyridine: Application to the Broad-Scope [3 + 2] Cycloaddition of Cyclopropanes and Alkenes.

In contrast to the extensive but non-recyclable use of tetraalkoxydiboron(4) compounds as stoichiometric reagents in diverse reactions, this article reports an atom-economical reaction using a commercial diboron(4) as the catalyst. The key to success was designing a catalytic cycle for radical [3 + 2] cycloaddition involving a pyridine cocatalyst to generate from the diboron(4) catalyst and reversibly mediate the transfer of boronyl radicals. In comparison with known [3 + 2] cycloaddition with transition metal-based catalysts, the current reaction features not only metal-free conditions, inexpensive and stable catalysts, and simple operation but also remarkably broadened substrate scope. In particular, previously unusable cyclopropyl ketones without an activating group and/or alkenes with 1,2-disubstitution and 1,1,2-trisubstitution patterns were successfully used for the first time. Consequently, challenging cyclopentane compounds with various levels of substitution (65 examples, 57 new products, up to six substituents at all five ring atoms) were readily prepared in generally high to excellent yield and diastereoselectivity. The reaction was also successfully applied in concise formal synthesis of an anti-obesity drug and building natural product-like complex bridged or spirocyclic compounds. Mechanistic experiments and computational investigation support the proposed radical relay catalysis featuring a pyridine-assisted boronyl radical catalyst. Overall, this work demonstrates the first approach to use tetraalkoxydiboron(4) compounds as catalysts and may lead to the development of new, green, and efficient transition metal-like boron-catalyzed organic reactions.

Balancing skeleton and functional groups in total syntheses of complex natural products: a case study of tigliane, daphnane and ingenane diterpenoids.

Total synthesis of natural products has greatly contributed to natural product research, organic synthesis and drug discovery and development. However, in most cases, the efficiency of total synthesis is far from sufficient for direct practical industrial application. Thus, designing a concise and efficient synthetic route with balanced efforts between building the complex skeleton and introducing functional groups is highly desirable. In this critical review, we first present an introduction of this issue and a philosophical framework that cover possible synthetic approaches. Next, we have chosen the biogenetically closely related, biologically important and synthetically extremely challenging natural products, tiglianes, daphnanes and ingenanes as the particular case for the discussion, since in the past 40 years many synthetic approaches have been reported. The successes and pitfalls included therefore serve as the basis to draw some conclusions that may inspire future development in this area.

Total Synthesis of Prostratin, a Bioactive Tigliane Diterpenoid: Access to Multi-Stereocenter Cyclohexanes from a Phenol.

Tiglianes such as prostratin and related diterpenoids are biologically significant natural molecules and long-standing targets for organic synthesis community. Due to the complex polycyclic scaffolds, high oxygenation level, and dense functional groups and stereocenters, their de novo chemical syntheses still face formidable challenges despite extensive efforts in the past 40 years. This account details the development of a modular and concise synthesis of prostratin, a potent anti-HIV and anticancer agent. The key approach in this synthesis involved a sequence of oxidative dearomatization and sequential stereoselective installation of peripheral groups to rapidly build the contiguously substituted cyclohexane C-ring. Inspired by Wender's work, an acid- and solvent-controlled stereodivergent formation of cyclopropane D-ring was developed. Mechanistic investigations by computational methods revealed that the competition between intra- and intermolecular hydrogen bonding led to different conformations, thus favoring different protonation processes. The designed and unexpected chemistry along this campaign reflected the uniqueness of the natural structures and should be amenable to future chemical syntheses of related complex polycyclic molecules.

A unified approach for divergent synthesis of contiguous stereodiads employing a small boronyl group.

Acyclic contiguous stereocenters are frequently seen in biologically active natural and synthetic molecules. Although various synthetic methods have been reported, predictable and unified approaches to all possible stereoisomers are rare, particularly for those containing non-reactive hydrocarbon substituents. Herein, a ß-boronyl group is employed as a readily accessible handle for predictable α-functionalization of enolates with either syn or anti selectivity depending on reaction conditions. Contiguous tertiary-tertiary and tertiary-quaternary stereocenters are thus accessed in generally good yields and diastereoselectivity. Based on experimental and computational studies, mechanism for syn selective alkylation is proposed, and Bpin (pinacolatoboronyl) behaves as a smaller group than most carbon-centered groups. The synthetic utility of this methodology is demonstrated by preparation of several key intermediates for bioactive molecules.

Recent Advances in Continuous-Flow Enantioselective Catalysis.

The increased demand for more efficient, safe, and green production in fine chemical and pharmaceutical industry calls for the development of continuous-flow manufacturing, and for chiral chemicals in particular, enantioselective catalytic processes. In recent years, this emerging direction has received considerable attention and has seen rapid progress. In most cases, catalytic enantioselective flow processes using homogeneous, heterogeneous, or enzymatic catalysts have shown significant advantages over the conventional batch mode, such as shortened reaction times, lower catalysts loadings, and higher selectivities in addition to the normal merits of non-enantioselective flow operations. In this Minireview, the advancements, key strategies, methods, and technologies developed the last six years as well as remaining challenges are summarized.

An Internet-Based Self-Testing Model (Easy Test): Cross-Sectional Survey Targeting Men Who Have Sex With Men Who Never Tested for HIV in 14 Provinces of China.

BACKGROUND: With China's explosive internet growth, activities such as socializing and partner seeking among men who have sex with men (MSM) has also become Web based through popular services such as Blued. This creates a new mode of health promotion with the potential to instantly reach large numbers of MSM, including those who rarely access traditional offline testing facilities. OBJECTIVE: This study aimed to assess the feasibility of the Easy Test in increasing access and uptake of HIV testing and treatment services among MSM and to identify demographic and behavioral predictors of program uptake to inform future implementation. METHODS: A feasibility study of the Easy Test model was conducted from October 2017 to December 2017 in 14 Chinese provinces. Applicants who provided informed consent completed a self-administered questionnaire and submitted a US $5 deposit to have the free test kit delivered to their homes. Orders were then received, processed, and posted by volunteers from local community-based organizations. Once applicants submitted images of their test results, the deposit was refunded to the applicant. Those whose test results were deemed to be HIV-positive were then connected to a peer navigator to accompany the individual to follow-up medical services. A chi-squared trend test was used to assess the relationship between lifetime HIV testing volume and HIV prevalence. Logistic regression models were used to identify independent risk factors associated with two outcomes: (1) never having tested for HIV and (2) receiving an HIV-positive result. RESULTS: A total of 879 individuals submitted Web-based requests for test kits. Their median age was 28 (interquartile range 24-34 years); 69.3% (609/879) had at least a college education, and 51.5% (453/879) had a monthly income between US $450 to $750; 77.7% (683/879) of the applicants submitted images of their test results, among whom 14.3% (98/683) had an HIV-positive result. Among the 42.9% (293/683) who were first-time testers, the HIV prevalence was 18.8% (55/293). Nearly three-quarters (71/98, 72.4%) of those with a positive test result were connected with a peer navigator and enrolled in treatment. Among the first-time testers, having multiple sexual partners (2-3 sexual partners: adjusted odds ratio [aOR] 2.44, 95% CI 1.08-5.50; 4 or above sexual partners: aOR 3.55, 95% CI 1.18-10.68) and reporting inconsistent condom use in the previous 3 months (aOR 7.95, 95% CI 3.66-17.26) were both associated with an HIV-positive result. An inverse dose response relationship between lifetime HIV testing volume and HIV prevalence was also observed in this study (χ23=55.0; P<.001). CONCLUSIONS: The Easy Test model reached a larger portion of first-time testers, many who reported higher risk sexual behaviors. This highlights the potential for an internet-based self-test model to increase access to HIV treatment services for HIV-positive MSM in China.

Spatial Analysis of the Human Immunodeficiency Virus Epidemic among Men Who Have Sex with Men in China, 2006-2015.

BACKGROUND: Studies have shown a recent upsurge in human immunodeficiency virus (HIV) burden among men who have sex with men (MSM) in China, especially in urban areas. For intervention planning and resource allocation, spatial analyses of HIV/AIDS case-clusters were required to identify epidemic foci and trends among MSM in China. METHODS: Information regarding MSM recorded as HIV/AIDS cases during 2006-2015 were extracted from the National Case Reporting System. Demographic trends were determined through Cochran-Armitage trend tests. Distribution of case-clusters was examined using spatial autocorrelation. Spatial-temporal scan was used to detect disease clustering. Spatial correlations between cases and socioenvironmental factors were determined by spatial regression. RESULTS: Between 2006 and 2015, in China, 120 371 HIV/AIDS cases were identified among MSM. Newly identified HIV/AIDS cases among self-reported MSM increased from 487 cases in 2006 to >30 000 cases in 2015. Among those HIV/AIDS cases recorded during 2006-2015, 47.0% were 20-29 years old and 24.9% were aged 30-39 years. Based on clusters of HIV/AIDS cases identified through spatial analysis, the epidemic was concentrated among MSM in large cities. Spatial-temporal clusters contained municipalities, provincial capitals, and main cities such as Beijing, Shanghai, Chongqing, Chengdu, and Guangzhou. Spatial regression analysis showed that sociodemographic indicators such as population density, per capita gross domestic product, and number of county-level medical institutions had statistically significant positive correlations with HIV/AIDS among MSM. CONCLUSIONS: Assorted spatial analyses revealed an increasingly concentrated HIV epidemic among young MSM in Chinese cities, calling for targeted health education and intensive interventions at an early age.

Mortality among People Living with HIV and AIDS in China: Implications for Enhancing Linkage.

To assess the patterns and predictors of AIDS-related mortality and identify its correlates among adult people living with HIV/AIDS (PLWHA) in China, a retrospective record-based cohort study was conducted among 18 years or older PLWHA, who had at least one follow up reported to the national database between January-1989 and June-2012. Cumulative Incidence Function was used to calculate AIDS-related mortality rate. Gray's test was used to determine the variation in cumulative incidence across strata. The Fine and Gray model was used to measure the burden of cumulative incidence of AIDS-related mortality and strength of its association with potential correlates. Among 375,629 patients, 107,634 died during study period, of which 54,759 (50.87%) deaths were AIDS-related. Cumulative mortality rates of AIDS-related death at one, two, five, 10 and 15 years post-diagnosis were 5.7%, 8.2%, 14.3%, 22.9% and 30.9%, respectively. Among PLWHA, male gender, ethnic minority and having AIDS were associated with significantly higher mortality. Further, homosexual transmission, being on ART and increasing CD4-testing frequency were associated with lower mortality. To reduce mortality among PLWHA, efficient interventions targeting males, ethnic minority, heterosexually infected and AIDS patients should be combined with immunologic monitoring, enhancement of coverage of HIV-testing and ART.

Estimating HIV incidence among key affected populations in China from serial cross-sectional surveys in 2010-2014.

INTRODUCTION: HIV incidence is an important measure for monitoring the development of the epidemic, but it is difficult to ascertain. We combined serial HIV prevalence and mortality data to estimate HIV incidence among key affected populations (KAPs) in China. METHODS: Serial cross-sectional surveys were conducted among KAPs from 2010 to 2014. Trends in HIV prevalence were assessed by the Cochran-Armitage test, adjusted by risk group. HIV incidence was estimated from a mathematical model that describes the relationship between changes in HIV incidence with HIV prevalence and mortality. RESULTS: The crude HIV prevalence for the survey samples remained stable at 1.1 to 1.2% from 2010 to 2014. Among drug users (DUs), HIV prevalence declined from 4.48 to 3.29% (p<0.0001), and among men who have sex with men (MSM), HIV prevalence increased from 5.73 to 7.75% (p<0.0001). Changes in HIV prevalence among female sex workers (FSWs) and male patients of sexually transmitted disease clinics were more modest but remained statistically significant (all p<0.0001). The MSM population had the highest incidence estimates at 0.74% in 2011, 0.59% in 2012, 0.57% in 2013 and 0.53% in 2014. Estimates of the annual incidence for DUs and FSWs were very low and may not be reliable. CONCLUSIONS: Serial cross-sectional prevalence data from representative samples may be another approach to construct approximate estimates of national HIV incidence among key populations. We observed that the MSM population had the highest incidence for HIV among high-risk groups in China, and we suggest that interventions targeting MSM are urgently needed to curb the growing HIV epidemic.

Causes of Death among AIDS Patients after Introduction of Free Combination Antiretroviral Therapy (cART) in Three Chinese Provinces, 2010-2011.

INTRODUCTION: Although AIDS-related deaths have had significant economic and social impact following an increased disease burden internationally, few studies have evaluated the cause of AIDS-related deaths among patients with AIDS on combination anti-retroviral therapy (cART) in China. This study examines the causes of death among AIDS-patients in China and uses a methodology to increase data accuracy compared to the previous studies on AIDS-related mortality in China, that have taken the reported cause of death in the National HIV Registry at face-value. METHODS: Death certificates/medical records were examined and a cross-sectional survey was conducted in three provinces to verify the causes of death among AIDS patients who died between January 1, 2010 and June 30, 2011. Chi-square analysis was conducted to examine the categorical variables by causes of death and by ART status. Univariate and multivariate logistic regression were used to evaluate factors associated with AIDS-related death versus non-AIDS related death. RESULTS: This study used a sample of 1,109 subjects. The average age at death was 44.5 years. AIDS-related deaths were significantly higher than non-AIDS and injury-related deaths. In the sample, 41.9% (465/1109) were deceased within a year of HIV diagnosis and 52.7% (584/1109) of the deceased AIDS patients were not on cART. For AIDS-related deaths (n = 798), statistically significant factors included CD4 count <200 cells/mm3 at the time of cART initiation (AOR 1.94, 95%CI 1.24-3.05), ART naïve (AOR 1.69, 95%CI 1.09-2.61; p = 0.019) and age <39 years (AOR 2.96, 95%CI 1.77-4.96). CONCLUSION: For the AIDS patients that were deceased, only those who initiated cART while at a CD4 count ≥200 cells/mm3 were less likely to die from AIDS-related causes compared to those who didn't initiate ART at all.

Spatiotemporal Scan and Age-Period-Cohort Analysis of Hepatitis C Virus in Henan, China: 2005-2012.

BACKGROUND: Studies have shown that hepatitis C virus (HCV) infection increased during the past decades in China. However, little evidence is available on when, where, and who were infected with HCV. There are gaps in knowledge on the epidemiological burden and evolution of the HCV epidemic in China. METHODS: Data on HCV cases were collected by the disease surveillance system from 2005 to 2012 to explore the epidemic in Henan province. Spatiotemporal scan statistics and age-period-cohort (APC) model were used to examine the effects of age, period, birth cohort, and spatiotemporal clustering. RESULTS: 177,171 HCV cases were reported in Henan province between 2005 and 2012. APC modelling showed that the HCV reported rates significantly increased in people aged > 50 years. A moderate increase in HCV reported rates was observed for females aged about 25 years. HCV reported rates increased over the study period. Infection rates were greatest among people born between 1960 and 1980. People born around 1970 had the highest relative risk of HCV infection. Women born between 1960 and 1980 had a five-fold increase in HCV infection rates compared to men, for the same birth cohort. Spatiotemporal mapping showed major clustering of cases in northern Henan, which probably evolved much earlier than other areas in the province. CONCLUSIONS: Spatiotemporal mapping and APC methods are useful to help delineate the evolution of the HCV epidemic. Birth cohort should be part of the criteria screening programmes for HCV in order to identify those at highest risk of infection and unaware of their status. As Henan is unique in the transmission route for HCV, these methods should be used in other high burden provinces to help identify subpopulations at risk.

Copper-catalyzed aerobic cascade cycloamination and acyloxylation: a direct approach to 4-acyloxy-1H-pyrazoles.

A novel direct transformation of hydrazones to acyloxylated pyrazoles by copper-catalyzed regioselective olefinic C(sp(2))-H bond cycloamination and acyloxylation was performed under mild conditions, which combines the formation of the pyrazole skeleton and installation of an acyloxyl group in a single step, using facile carboxylic acids as the acyloxylation reagents.

[Characteristics of HIV transmission through heterosexual contact in China, 2008-2014].

OBJECTIVE: To understand the epidemiological characteristics and changing patterns of HIV transmission through heterosexual contact since 2008, and to project the influences of heterosexual transmission mode on the HIV epidemic in China. METHODS: Demographic data and history of exposure in newly identified HIV/AIDS cases aged 15 years or older, through heterosexual transmission mode from 2008 to 2014, were collected and analyzed. RESULTS: The number of HIV/AIDS cases caused by heterosexual transmission increased from 23 402 in 2008, to 68 671 in 2014. The proportion of heterosexual transmission mode increased from 8.7% in 2008 to 66.4% in 2014. Among these cases, the proportion of males increased from 55.3% in 2008 to 68.2% in 2014. Among those who reported acquiring HIV through heterosexual contact, the proportion of cases through extramarital sexual acts out of all the newly report ones, increased from 78.2% in 2008 to 88.2% in 2014. This mode of infection accounted for 85.2% in the age 15 to 49 years group, comparing to 84.2% in the age group of 50 years old or above. The proportion of reported HIV infections through extramarital sexual acts appeared 93.8% on males while 69.0% on females, with statistically significant difference (χ(2)=36 000.000, P<0.001). CONCLUSION: As the predominant factor of HIV/AIDS epidemic, currently in China, heterosexual transmission showed diversities in different sub-epidemic areas, gender or age groups. Tailored strategies were urgently needed for health education and highrisk behavioral intervention, according to the local epidemic driven factors, respectively.

HIV epidemic among drug users in China: 1995-2011.

AIM: To describe trends in the HIV epidemic among drug users (DUs) in China from 1995 to 2011. DESIGN, SETTING AND PARTICIPANTS: Data sets from China's national HIV/AIDS case reporting and sentinel surveillance systems as of December 2011 were used separately for descriptive analysis. MEASURES: Changes in the geographic distribution of the number of HIV cases and HIV prevalence among injecting drug users (IDUs) and non-IDUs were examined. We also analysed changes in HIV prevalence among the broader DU population, and drug use-related behaviours including types of drugs used, recent injecting and recent needle sharing in the context of the rapid scale-up of DU sentinel sites and national harm reduction programmes. FINDINGS: The HIV epidemic among China's DUs is still highly concentrated in five provinces. Here, HIV prevalence peaked at 30.3% [95% confidence interval (CI)=28.6, 32.1] among IDUs in 1999, and then gradually decreased to 10.9% (95% CI=10.6, 11.2) by 2011. We observed a rapid increase in the use of 'nightclub drugs' among DUs from 1.3% in 2004 to 24.4% in 2011. A decline in recent needle sharing among current IDU from 19.5% (95% CI=19.4, 19.6) in 2006 to 11.3% (95% CI=11.2, 11.4) in 2011 was found to be correlated with the rapid scale-up of methadone maintenance treatment (MMT; r(4)=-0.94, P=0.003) harm reduction efforts. CONCLUSIONS: While HIV prevalence and needle sharing among current injecting drug users in China have declined dramatically and are correlated with the scale-up of national harm reduction efforts, the recent, rapid increased use of 'nightclub drugs' presents a new challenge.

Spatial analysis on hepatitis C virus infection in mainland China: from 2005 to 2011.

BACKGROUND: The burden of Hepatitis C virus (HCV) has become more and more considerable in China. A macroscopic spatial analysis of HCV infection that can provide scientific information for further intervention and disease control is lacking. METHODS: All geo-referenced HCV cases that had been recorded by the China Information System for Disease Control and Prevention (CISDCP) during 2005-2011 were included in the study. In order to learn about the changes of demographic characteristics and geographic distribution, trend test and spatial analysis were conducted to reflect the changing pattern of HCV infection. RESULTS: Over 770,000 identified HCV infection cases had specific geographic information during the study period (2005-2011). Ratios of gender (Male/Female, Z-value  = -18.53, P<0.001), age group (≤30 years old/≥31 years old, Z-value  = -51.03, P<0.001) and diagnosis type (Clinical diagnosis/Laboratory diagnosis, Z-value  = -130.47, P<0.001) declined. HCV infection was not distributed randomly. Provinces Henan, Guangdong, Guangxi, Xinjiang, and Jilin reported more than 40,000 HCV infections during 2005 to 2011, accounting for 43.91% of all cases. The strength of cluster of disease was increasing in China during the study period. Overall, 11 provinces had once been detected as hotspots during 7 years, most of which were located in the central or border parts of China. Tibet, Qinghai, Jiangxi were the regions that had coldspots. CONCLUSIONS: The number of clustering of HCV infection among older adults increased in recent years. Specific interventions and prevention programs targeting at main HCV epidemic areas are urgently in need in mainland China.

[Trend on HIV prevalence and risk behaviors among men who have sex with men in China from 2010 to 2013].

OBJECTIVE: To understand the trends on HIV and syphilis infections, as well as on risk behaviors and intervention among MSM in China from 2010 to 2013 so as to provide information for the development of intervention strategies for MSM. METHODS: Study population involved MSM who were recruited for the national HIV sentinel surveillance between 2010 and 2013. Demographic information, HIV related risk behaviors, and results on HIV and syphilis infections were described and trend analysis was performed. RESULTS: Between 2010 and 2013, the total number of MSM under survey was 149 848. As for sources of the studied population, 12.3% of them were from public bathrooms (Group A), 30.1% from internet (Group B), and 57.5% were others (Group C). Proportions of three groups were similar between 2010 and 2013. The proportion of always using condom in the last six months increased from 30.2% to 37.8%, from 34.7% to 42.9% and from 35.3% to 43.1% in group A, B or C (trend:P < 0.01), from 2010 to 2013. The proportion of using condom in group A was the lowest among the three groups. The prevalence rate of HIV increased from 7.8% in 2010 to 9.2% in 2013 among group A, from 5.0% in 2010 to 6.8% in 2013 among group B, from 5.6% in 2010 to 6.5% in 2013 among group C(trend:P < 0.01). The prevalence rate of syphilis decreased from 13.2% in 2010 to 9.5% in 2013 among group A, from 6.1% in 2010 to 5.7% in 2013 among group B, from 8.7% in 2010 to 6.2% in 2013 among group C (trend:P < 0.01). In this MSM population, 77.1% of them were at age 21-40, 9.4% were at age 41-50 and 2.8% were older than 50 years of age. Both the prevalence rates of HIV and syphilis were the highest-10.1% and 13.6%, among age group of over 50s, respectively. CONCLUSION: HIV prevalence among MSM increased rapidly in the last four years, especially in older age groups and from public bathrooms. More intervention efforts should be targeting on MSM with the above mentioned characters.

Diversity of HIV/AIDS epidemic in China: a result from hierarchical clustering analysis and spatial autocorrelation analysis.

OBJECTIVE: To find out the diversity of HIV/AIDS epidemic among different areas in China according to their varied epidemic characteristics. DESIGN AND METHODS: Seventeen provincial variables, generated from original HIV/AIDS epidemic data and socioeconomic indicators to indicate HIV/AIDS epidemic characteristics, were introduced to hierarchical clustering analysis to form subepidemic areas. Then spatial autocorrelation analysis was applied to show the clustering distribution of cases from different most-at-risk populations. RESULTS: Three HIV/AIDS subepidemic areas (A, B, C) were formed, each of which was further divided into two clusters, showing the diversity of HIV/AIDS epidemic in China. A1 was the earliest and severest HIV/AIDS epidemic area and occupied 37% hotspot counties. The epidemic in A1 was driven by IDU in its early period and heterosexual transmission later. Henan, the only province in A2, characterized by its HIV/AIDS epidemic among former plasma donors during the early 1990s, presented strong spatial clustering of blood/plasma transmission occupying 80% blood/plasma hotspots. The epidemic within B3, located in southwest China, was driven by IDU and heterosexual populations, and recently by MSM. The epidemic within B4, covering all four municipalities, had been largely spread among MSM since 2005. B3 and B4 occupied 76% MSM hotspots. For C5 and C6, only sporadic HIV/AIDS infections occurred in the last years among former plasma donors and heterosexual populations, whereas the prevalence among MSM had been increasing. CONCLUSION: China's different HIV/AIDS subepidemic areas had obvious diversity of affected populations, which should be considered when determining prevention policies.