Using molecular network analysis to understand current HIV-1 transmission characteristics in an inland area of Yunnan, China.

HIV-1 molecular surveillance provides a new approach to explore transmission risks and targeted interventions. From January to June 2021, 663 newly reported HIV-1 cases were recruited in Zhaotong City, Yunnan Province, China. The distribution characteristics of HIV-1 subtypes and HIV-1 molecular network were analysed. Of 542 successfully subtyped samples, 12 HIV-1 strains were identified. The main strains were CRF08_BC (47.0%, 255/542), CRF01_AE (17.0%, 92/542), CRF07_BC (17.0%, 92/542), URFs (8.7%, 47/542), and CRF85_BC (6.5%, 35/542). CRF08_BC was commonly detected among Zhaotong natives, illiterates, and non-farmers and was mostly detected in Zhaoyang County. CRF01_AE was frequently detected among married and homosexual individuals and mostly detected in Weixin and Zhenxiong counties. Among the 516 pol sequences, 187 (36.2%) were clustered. Zhaotong natives, individuals aged ≥60 years, and illiterate individuals were more likely to be found in the network. Assortativity analysis showed that individuals were more likely to be genetically associated when stratified by age, education level, occupation, and reporting area. The genetic diversity of HIV-1 reflects the complexity of local HIV epidemics. Molecular network analyses revealed the subpopulations to focus on and the characteristics of the risk networks. The results will help optimise local prevention and control strategies.

The characteristics of pretreatment HIV-1 drug resistance in western Yunnan, China.

HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017-2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6-10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6-7.4%), which is below the threshold (⩾10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.

Spatial clusters of HIV-1 genotypes in a recently infected population in Yunnan, China.

BACKGROUND: As a gateway for HIV-1 in China, Yunnan has experienced dramatic changes in HIV-1 epidemics, during which HIV-1 genotypes have become complex. To track dynamic changes in HIV-1 genotypes, an HIV-1 molecular epidemiological study was implemented in the recently infected population in Yunnan. METHODS: From 6,357 HIV-1-positive samples diagnosed during the first half of 2015 in Yunnan, 586 samples were identified as recent infections with BED-capture enzyme immunoassay (CEIA) and were subjected to phylogenetic analyses. Spatial scanning analyses for the main HIV-1 genotypes were also performed. RESULTS: Among the 439 specimens successfully genotyped, more than ten genotypes were detected, including CRF08_BC (45.3%), CRF07_BC (19.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (11.4%), subtype C (2.1%), CRF85_BC (1.1%), CRF55_01B (0.9%), subtype B (0.5%), CRF64_BC (0.5%), CRF59_01B (0.2%), CRF83_cpx (0.2%) and CRF87_cpx (0.2%). Females, Chinese, heterosexual contact and intravenous drug injection were significantly associated with CRF08_BC infection; homosexual contact was significantly associated with CRF01_AE and CRF07_BC infection; males and non-Chinese had a higher risk of URF infection than females. Among all HIV-1 genotypes, the geographic coverage of CRF08_BC was the largest. For CRF08_BC, CRF07_BC, URFs and CRF01_AE, spatial clusters were detected. The two CRF08_BC clusters and one URF cluster were associated with heterosexual transmission, and two of CRF01_AE clusters were associated with homosexual transmission. Transmitted drug resistance (TDR)-associated mutations were detected in 2.4% of individuals. CONCLUSIONS: The diversity of HIV-1 genotypes increased in recent infections because of a long-term HIV-1 epidemic in Yunnan. The predominant HIV-1 strains showed distinct demographic characteristics and formed spatial clusters. These findings improved our understanding of the evolution of HIV-1 in Yunnan and provided information for further HIV-1 control and prevention.

Demographic characteristics and spatial clusters of recent HIV-1 infections among newly diagnosed HIV-1 cases in Yunnan, China, 2015.

BACKGROUND: The characteristics of recent HIV infections can provide the information about the dynamics of HIV transmission. Yunnan is one of the provinces hardest-hit by HIV-1 in China. To further understand the characteristics of the HIV-1 epidemic in Yunnan, we analyzed the prevalence of recent HIV-1 infections among newly diagnosed cases, identified the associated factors and explored the spatial distribution of recent HIV-1 infections. METHODS: Residual plasma samples from HIV-1 diagnostic tests were preserved. The associated information was collected from China HIV/AIDS case reporting system. Recent HIV-1 infections were estimated by combining the information about disease progression and BED- capture enzyme immunoassay (CEIA). The proportions of recent HIV-1 infections among newly diagnosed cases stratified by demographic characteristics were analyzed. The spatial clusters of recent HIV-1 infections were investigated by spatial scan statistics. RESULTS: Among 6119 HIV/AIDS cases were newly reported between January 2015 and June 2015 in Yunnan Province, 9.3% (570/6119) were estimated as recent infections. Female, aged below 25 years and homosexual contact were more associated with the higher proportion of recent HIV-1 infections. Among the different demographic sub-groups, men who have sex with men (MSM) aged < 25 years and ≥ 50 years had a higher chance of being diagnosed as recent infections, heterosexually infected men aged ≥25 years had a lower chance of being diagnosed as recent infections. In the sub-groups with different screening approaches, the highest proportion of recent infections (16.1%) was found among women diagnosed by testing during pregnancy and childbirth. In the sub-groups with different contact histories, the higher proportion of recent infections was found among the female cases having commercial heterosexual contacts (16.4%) and MSM (19.7%). The statistically significant spatial clusters of recent infections attributed to heterosexual contact, homosexual contact and intravenous drug injection were identified, respectively. CONCLUSIONS: The investigation of recent HIV infections among newly diagnosed cases supplements the routine HIV surveillance, and reveals the characteristics of ongoing HIV transmission. Our finding identified the potential sub-populations and geographic areas in need of services or improved interventions.

Monetary incentives for provision of syphilis screening, Yunnan, China.

PROBLEM: Early detection of syphilis-infected people followed by effective treatment is essential for syphilis prevention and control. APPROACH: Starting in 2010 the local health authority in Yunnan province, China, developed a network of 670 service sites for syphilis testing, diagnosis and treatment or for testing-only with referral for further diagnosis and treatment. Point-of-care tests for syphilis and syphilis interventions were integrated into the existing human immunodeficiency virus (HIV) prevention and control programme. To improve the syphilis services, a pay-for-performance scheme was introduced in which providers were paid for testing and treating patients. LOCAL SETTING: Yunnan province is the region hardest hit by HIV infection and disproportionately burdened with syphilis cases in China. RELEVANT CHANGES: The proportion of attendees at voluntary counselling and testing clinics who were tested for syphilis increased from 46.2% (32 877/71 162) in 2010 to 98.2% (68 012/69 259) in 2015. Syphilis-infected cases treated with the recommended therapy increased from 26.6% (264/993) in 2010 to 82.5% (453/549) in 2015 at designated testing, diagnosis and treatment sites. LESSONS LEARNT: The strategy greatly increased the uptake of syphilis testing and treatment among people at risk. Introduction of point-of-care tests for syphilis increased coverage of the testing services. Introduction of a pay-for-performance scheme seemed to motivate health-care providers to undertake syphilis intervention services.

The changing trends of HIV-1 prevalence and incidence from sentinel surveillance of five sub-populations in Yunnan, China, 2001-2010.

BACKGROUND: Yunnan is one of the provinces hardest-hit by HIV in China. To understand HIV epidemic dynamics and evaluate prevention effectiveness, we studied the changing trends in HIV-1 prevalence and incidence among five sub-populations in Yunnan. METHODS: Consecutive sentinel surveillances were conducted among people who inject drugs (PWID), male sexually transmitted diseases (STD) clinic attendees, and pregnant women for 2001-2010,female sex workers (FSWs) for 2007-2010, men who have sex with men (MSM) for 2008-2010. For the newly diagnosed HIV-seropositive samples, the recent infections were determined with BED-capture enzyme immunoassay (BED-CEIA), based on which HIV incidence was calculated for each sub-population using McDougal algorithm. RESULTS: From 231,117 individuals, 6,107 HIV-positive samples were tested with BED-CEIA, among which 964 samples were identified as recent infections. In PWID, HIV prevalence for 2001-2010 was between 27.16% and 18.35%, while the estimated incidence rate significantly decreased from 11.68% in 2001 to 1.70% in 2010. Among male STD clinic attendees, both the HIV prevalence (from 3.62% in 2001 to 1.73% in 2010) and incidence (from 1.10% in 2001 to 0.40% in 2010) showed a significant decreasing trend. In FSWs, the HIV prevalence for 2007-2010 kept stable (between 2.46% and 1.95%), while the HIV incidence significantly decreased (from 0.71% in 2007 to 0.31% in 2010). In MSM, the HIV prevalence (between 11.78% and 9.42%) and incidence (between 6.01% and 8.38%) remained stable at a relatively high level for 2008-2010. In pregnant women, the HIV prevalence (between 0.44% and 0.30%) and incidence (between 0.15% and 0.08%) remained stable for 2001-2010. CONCLUSION: The HIV incidences in PWID, male STD clinic attendees and FSWs showed the decreasing trend, supporting a positive effect of prevention strategies for these sub-populations. MSM with the highest HIV incidence have become the sub-population most at risk. In most sub-populations, the HIV prevalence did not decline, suggesting the disease burden is still heavy. These findings are valuable for developing HIV prevention strategies in Yunnan.

[Research on the digit ratio of fixed partner and the multi-partner men who have sex with men].

OBJECTIVE: To investigate the digit ratio of men who have sex with men (MSM), and the relationship between digit ratio and the partner types of MSM. METHODS: Participants were required from Yunnan Rainbow Sky, a community organization that specialized in HIV testing, intervention and counseling services for MSM between December 2014 and April 2015. Inclusion criteria of MSM as the following: more than 18 years old; men who have had sex with men; HIV test was negative. Exclusion criteria were as this: those who couldn't attend the research due to disability. Eventually, there were 115 MSM participated in the research. According to the nationality, we adopted 1:1 matched case-control study, and we selected 115 men as control group. According to the partner number of MSM, the MSM were divided into two groups. One group was fixed partner and another was multi-partner. We used a questionnaire to collect the demographic characteristics, knowledge about HIV/AIDS, sexual behaviors during nearly 6 months, sexual orientation, the places where looked for sex partners, sex roles, drug use, preventive services etc. Then, the physical measurements were used to measure the length from second to the fifth finger in MSM group and control group. The results were expressed as nD. The chi-square test was used to compare the demographic differences between MSM group and the control group, and the T-test was used to compare the digit ratio between two groups. RESULTS: Among 115 MSM, there were 26% (30/115) MSM who had a fixed partner, and there were 74% (85/115) MSM who had multi-partner. The mean values of digit ratio of MSM presented a trend as 2D:3D < 2D:4D < 3D:4D < 2D:5D < 4D:5D < 3D:5D. The right 2D:4D and 2D:5D of MSM were 0.957 7 ± 0.048 1 and 1.229 8 ± 0.083 4, and the mean value was significasntly higher than control group (0.941 4 ± 0.038 0 and 1.204 1 ± 0.069 5, t values were 2.84, 2.54 and P values were 0.005, 0.012). The right 2D:4D of the fixed partner group and multi-partner group among MSM were 0.962 2 ± 0.051 0 and 0.956 1 ± 0.047 3, respectively, and the mean values were significantly higher than control group (t values were 2.98, 2.83; P values were 0.027, 0.015). CONCLUSION: The proportion of multi-partner MSM was higher, so MSM at a high risk of being HIV infected. Right 2D:4D could be used as a biomarker of the MSM in Kunming, but couldn't reflect the features of MSM whether he has a fixed partner or has several partners.

[Analysis of the risky behaviors among HIV positive female sex workers].

OBJECTIVE: To analyze the characteristics of risky behaviors among different age groups of HIV positive female sex workers, and to explore the strengthening of their management. METHODS: From January to June 2014, 22 814 female sex workers were investigated and tested HIV in 117 sentinel surveillance sites in Yunnan Province, and 181 were confirmed to be HIV antibody positive, who accepted questionnaire surveys. According to the age, the participants were divided into the < 35 years old age group and ≥ 35 years old age group. The demographic characteristics, knowledge about HIV/AIDS and related risk behaviors characteristics of the two groups were obtained via questionnaire surveys among 181 HIV positive female sex workers, and in-depth qualitative interviews were conducted from among 12 HIV positive sex workers. RESULTS: HIV antibody positive rate was 0.8% (181), the age of the 181 subjects were (35.83 ± 9.17) years old, 76 cases (42.0%) were < 35 years old, and 105 cases (58.0%) were ≥ 35 years old. The differences of marital status, workplace class, the last work site among two groups were statistically significant (χ(2) = 20.80, 28.32, 7.83; P < 0.001, P < 0.001, P = 0.020, respectively). Among 181 HIV, the proportion of AIDS awareness was 95.6% (173); the proportion of drug use among ≥ 35 years old age group was 51.4% (54), which was higher than that in < 35 years old age group (34.2%, 26/76) (χ(2) = 5.30, P = 0.021). 96.7% (175) received condom promotion or HIV counseling and testing in the past year. The proportion of continuing to engage in sexual services over 5 years after HIV infection was 48.5% (51/105) and the proportion of receiving antiretroviral treatment was 69.5% (73/105) in ≥ 35 years old age group, which were higher than those in the < 35 age group (30.2% (23/76), 52.6% (40/76); χ(2) = 12.26, 5.36; P = 0.002, 0.021, respectively). In-depth interviews among 12 HIV positive female sex workers found that regular clients, not consistent use of condoms were the main cause of no condom use. Economic and livelihood factors are important reasons for continuing to engage in sexual services among HIV positive sex workers. CONCLUSION: HIV positive sex workers still have high risk behaviors including continuing to engage in commercial sexual service and no condom use after knowing their HIV infection status, and the proportion of using drugs in the ≥ 35 years old group was higher than that in < 35 years old group.

High prevalence of HIV and syphilis and associated factors among low-fee female sex workers in mainland China: a cross-sectional study.

BACKGROUND: The prevalence of HIV and syphilis among middle and high-fee female sex workers (FSWs) has been widely reported but little is known among low-fee FSWs. This study aims to determine the prevalence and associated factors of HIV and syphilis among low-fee FSWs in China. METHODS: A cross-sectional study design was used. A convenience sample of low-fee FSWs was recruited from venues by outreach workers in 12 cities. Structured questionnaire interviews and blood sampling for HIV and syphilis were carried out. Univariate and multivariate logistic regression were used for assessing potential associated factors. RESULTS: This study enrolled 781 low-fee FSWs. There were 37 (4.7%) HIV positive participants and 117 (15.0%) participants were infected with syphilis. Final multivariate analysis identified five factors associated with HIV infection: older age (OR:2.6, 95% CI:1.1-6.1), local household registration (OR:3.3, 95% CI:1.5-6.9), employed in Yunnan province (OR:2.7, 95% CI:1.1-6.7), soliciting in self-rented rooms and "market day" buildings (OR:3.9, 95% CI:1.5-10.0), injection drug use in the past 6 months (OR:13.5, 95% CI:4.5-40.1); and four factors associated with syphilis infection: older age (OR:1.8, 95% CI:1.2-2.9), employed in Yunnan province (OR:2.1, 95% CI:1.2-3.6), soliciting in self-rented rooms and "market day" buildings (OR:2.3, 95% CI:1.4-3.7) , and no consistent condom use with clients in the past 30 days (OR:1.6, 95% CI:1.0-2.6). CONCLUSIONS: A high prevalence of HIV and syphilis were found among low-fee FSWs. Those soliciting in self-rented rooms and "market day" buildings with the lowest income, and injection drug users (IDUs) in this population should take priority in further intervention strategies.

The changing face of HIV in China.

HIV has advanced from high-risk groups such as intravenous drug users to some in the general population, according to comprehensive new data from the south of China. What needs to be done to halt its spread?

[An analysis of high risk behaviors among female sex workers in Yunnan province in 2013].

OBJECTIVE: To understand the high risk behaviors of female sex workers (FSWs) in Yunnan province in 2013. METHODS: A cross-sectional investigation was conducted during April to June, 2013 in Yunnan province, census was used to the investigation where the number of FSWs was close to 200, while probability sampling was used where the number of FSWs was obviously over 200. A total of 25 574 cases were investigated, and data on demography and risk behaviors were obtained by questionnaires one by one. RESULTS: A total of 25 574 cases were investigated, AIDS awareness among FSWs in high-level places, middle-level places and low-level place were 98.8% (92/7 401), 98.6% (150/10 995), and 96.0% (281/6 655). FSWs from low-level place had a lower rate than those from the other two types of places (P < 0.01). The rate of condom use each time when having sex with clients within the recent one month among FESs from high-level places, middle-level places and low-level place were 93.4% (6 307/6 755), 93.8% (10 109/10 782) and 90.4% (6 053/6 697), and the FSWs working in low-level place had a lower rate than those from the other two types of places(P < 0.01). Multi-factor logistic regression analysis showed that the following had a lower rate of condom use: the FSWs working in low-level place (OR = 1.56, 95% CI:1.36-1.79; OR = 1.36, 1.16-1.59), over 30 years old (OR = 0.77, 95%CI:0.69-0.85), Yunnan citizen (OR = 0.88, 95% CI:0.77-1.00), minority (OR = 1.32, 95% CI:1.16-1.50), under senior high school (OR = 0.61, 95%CI:0.49-0.75), married (OR = 0.81, 95% CI:0.71-0.92), living together (OR = 0.70, 95% CI:0.51-0.96), divorced or lost spouses (OR = 0.81, 95% CI:0.65-1.02), worked less than 6 months in local areas (OR = 1.74, 95% CI:1.34-2.27), drug users (OR = 1.65, 95% CI:1.11-2.46), had not accepted HIV interventions (OR = 2.91, 95% CI:2.36-3.58), had no knowledge about AIDS (OR = 4.50, 95% CI:3.48-5.82). The main reasons for not using condoms were the clients' unwilling to use, which accounted for 47.62% (270/567). The total rate of drug use was 1.0% (264/25 567) and the FSWs working in middle-level places had the highest rate of injecting drugs, which accounted for 0.6% (70/11 141). The FSWs working in low-level places had a higher rate than those who worked in high-level places and middle-level places in venereal diseases, which accounted for 1.2% (85/6 934) (P < 0.01). The rate of receiving effective interventions was 96.7% (24 717/25 574), the rate of accepting treatment and clean needles among drug users was 21.6% (57/264). CONCLUSION: High risk behaviors were serious among the FSWs who worked in low-level places, especially among the olders, the minorities, people who had lower educational level, the new-comer and drug users, which indicated that more attention needs to be paid among these populations.

HIV-1 molecular networks and pretreatment drug resistance at the frontier of Yunnan Province, China.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174) and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men (MSM). The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170) and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

Reconstituting the epidemic history of HIV strain CRF01_AE among men who have sex with men (MSM) in Liaoning, northeastern China: implications for the expanding epidemic among MSM in China.

HIV CRF01_AE accounted for 84% of the recent infections among men who have sex with men (MSM) in Liaoning Province of northeastern China. CRF01_AE strains were grouped into two distinct clusters (designated clusters 1 and 2) that were also detected in other regions in China. Phylodynamics study revealed that these two CRF01_AE strains were independently introduced into the population of MSM in China in the early and mid-1990s. Our study elucidated unique features of dynamics and interrelationships of MSM epidemics in China.

Reducing HIV-related stigma in health care settings: a randomized controlled trial in China.

OBJECTIVES: The objective of the intervention was to reduce service providers' stigmatizing attitudes and behaviors toward people living with HIV. METHODS: The randomized controlled trial was conducted in 40 county-level hospitals in 2 provinces of China between October 2008 and February 2010. Forty-four service providers were randomly selected from each hospital, yielding a total of 1760 study participants. We randomized the hospitals to either an intervention condition or a control condition. In the intervention hospitals, about 15% of the popular opinion leaders were identified and trained to disseminate stigma reduction messages. RESULTS: We observed significant improvements for the intervention group in reducing prejudicial attitudes (P < .001), reducing avoidance intent towards people living with HIV (P < .001), and increasing institutional support in the hospitals (P = .003) at 6 months after controlling for service providers' background factors and clinic-level characteristics. The intervention effects were sustained and strengthened at 12 months. CONCLUSIONS: The intervention reduced stigmatizing attitudes and behaviors among service providers. It has the potential to be integrated into the health care systems in China and other countries.

Prospective cohort study of HIV incidence and molecular characteristics of HIV among men who have sex with men(MSM) in Yunnan Province, China.

BACKGROUND: Yunnan has the largest number of reported HIV/AIDS cases among all Chinese provinces, the reported prevalence of HIV among Yunnan men who have sex with men (MSM) passed 10%, while HIV incidence epidemic and molecular characteristics of new infected Yunnan MSM were not evaluated before. METHODS: An 18 months prospective followed up with a frequency of 3 month per visit were conducted among HIV seronegative MSM in Kunming cityduring 2009-2011. Interviewer-administrated questionnaires were carried out. Blood specimens were obtained to test for syphilis and HIV, in which HIV were evaluated by standard HIV enzyme immunoassay (EIA) and HIV nucleic acid amplification testing (NAAT). Near full-length regions of the HIV-1 were evaluated for subtyping, primary drug resistance mutations. RESULTS: During the follow-up 70.1% of the recruited 378 MSM retained in the cohort. Eleven MSM seroconverted to HIV and fifteen MSM seroconverted to syphilis. The HIV incidence and syphilis incidence was 3.5 (95% CI 1.8-6.2) cases /100 person year(PY) and 5.3 (95% CI 3.0-8.7) cases/100 PY, respectively. Multivariate analysis showed that baseline syphilis infection (aHR, 17.7), occupation (students vs. others [aHR, 5.7], retirees vs. others [aHR, 4.1]), bleeding experience after receptive anal intercourse (aHR,7.6), and minority ethnic(vs. Han) [aHR, 5.7] were independent risk factors for HIV seroconversion(each P<0.05). Among the 7/11 successfully amplified near full-length sequences, 71.4% (5/7) were CRF01_AE, and 28.6% (2/7) were CRF07_BC. Two HIV transmission pairs were detected among seroconverted minority ethnic MSM. CONCLUSIONS: HIV incidence was moderately high among Yunnan MSM. Yunnan province need to strengthen both HIV and syphilis screening among MSM population. Some subpopulations of MSM, such as students, retirees and minority ethnic groups require more HIV epidemic surveillance and strengthened behavior interventions. HIV subtypes and primary drug resistance should be continually monitored to track cross-group transmission of HIV strains.

[Evaluation of PIMA analyzer detecting CD4 cell count of venous and capillary blood in HIV-infected individuals].

OBJECTIVE: This study is aimed at evaluating the utility of the portable CD4 analyzers (PIMA). METHODS: The paired finger prick blood (25 µl) and 5 ml venous blood samples were collected from 196 HIV infected patients, who came to Yunnan CDC voluntary counseling and testing (VCT) clinic for CD4 test services, from May to August, 2012. The absolute CD4 cell counts were measured by PIMA (using venous and finger-prick blood) and by Calibur (using venous blood) as the reference. The PIMA and Calibur CD4 results were compared using the Wilcoxon matched-pairs test, and the Spearman's rank correlation coefficients were estimated. The Bland-Altman plots were used to assess the consistency of the two methods. RESULTS: The median absolute CD4 counts of 196 venous blood samples obtained by PIMA and by Calibur were 268 (range:169-403) cells/µl and 302 (range:181-474) cells/µl respectively, which showed significant difference (Z = -7.31, P < 0.01). The median absolute CD4 counts measured by PIMA and by Calibur (using 188 finger-prick and venous blood samples respectively) were 271 (range: 165-450) cells/µl and 304 (range:188-476) cells/µl, which also showed significant difference (Z = -7.60, P < 0.01). The CD4 counts obtained by PIMA CD4 analyzer (using venous and finger-prick blood) showed strong positive correlation with the CD4 counts obtained by the reference method (using venous blood), and the r values were 0.94 and 0.92 respectively (P < 0.01) . The mean biases (limit of agreement) were -38.7 (-210.9-133.5)cells/µl and -45.4 (-221.8-131.0) cells/µl, respectively.Using 350 CD4 counts as the threshold for ART treatment initiation, the sensitivity and specificity of PIMA were 99.1% and 79.3% for venous blood samples, and 97.2%and 78.5% for finger-prick blood samples, respectively. CONCLUSION: The CD4 counts obtained by PIMA are lower than that obtained by Calibur, while the sensitivity is high.

Genetic diversity and drug resistance among newly diagnosed and antiretroviral treatment-naive HIV-infected individuals in western Yunnan: a hot area of viral recombination in China.

BACKGROUND: The emergence of an HIV-1 epidemic in China was first recognized in Dehong, western Yunnan. Due to its geographic location, Dehong contributed greatly in bridging HIV-1 epidemics in Southeast Asia and China through drug trafficking and injection drug use; and also extensively to the HIV genetic diversity in Yunnan and China. We attempt to monitor HIV-1 in this area by studying the HIV-1 genetic distribution and transmitted drug resistance (TDR) in various at-risk populations. METHODS: Blood samples from a total of 320 newly HIV-1 diagnosed individuals, who were antiretroviral therapy (ART)-naive, were collected from January 2009 to December 2010 in 2 counties in Dehong. HIV-1 subtypes and pol gene drug resistance (DR) mutations were genotyped. RESULTS: Among 299 pol sequences successfully genotyped (93.4%), subtype C accounted for 43.1% (n=129), unique recombinant forms (URFs) for 18.4% (n=55), CRF01_AE for 17.7% (n=54), B for 10.7% (n=32), CRF08_BC for 8.4% (n=25) and CRF07_BC for 1.7% (n=5). Subtype distribution in patients infected by different transmission routes varied. In contract to the previous finding of CRF01_AE predominance in 2002-2006, subtype C predominated in both injecting drug users (IDUs) and heterosexually transmitted populations in this study. Furthermore, we found a high level of BC, CRF01_AE/C and CRF01_AE/B/C recombinants suggesting the presence of active viral recombination in the area. TDR associated mutations were identified in 4.3% (n=13) individuals. A total of 1.3% of DR were related to protease inhibitors (PIs), including I85IV, M46I and L90M; 0.3% to nucleoside reverse transcriptase inhibitors (NRTIs), including M184I; and 2.7% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), including K103N/S, Y181C, K101E and G190A. CONCLUSION: Our work revealed diverse HIV-1 subtype distributions and intersubtype recombinations. We also identified a low but significant TDR mutation rate among ART-naive patients. These findings enhance our understanding of HIV-1 evolution and are valuable for the development and implementation of a comprehensive public health approach to HIV-1 DR prevention and treatment in the region.

Uncovering the Impact of Control Strategies on the Transmission Pattern of SARS-CoV-2 - Ruili City, Yunnan Province, China, February-March 2022.

Introduction: The implementation of public health and social measures (PHSMs) was an effective option for controlling coronavirus disease 2019 (COVID-19). However, evidence is needed to evaluate these PHSMs' effects on the recently emerged variant Omicron. Methods: This study investigated variant Omicron BA.2's outbreak in Ruili City, Yunnan Province, China. The disease transmission dynamics, spatiotemporal interactions, and transmission networks were analyzed to illustrate the effect of PHSM strategies on Omicron spread. Results: A total of 387 cases were related to the outbreak. The time-varying reproduction number was synchronized with PHSM strategies. Spatiotemporal clustering strength presented heterogeneity and hotspots. Restricted strategies suppressed temporal and spatial relative risk compared with routine and upgraded strategies. The transmission network presented a steeper degree distribution and a heavier tail under upgraded strategies. Phase transformation and distinctive transmission patterns were observed from strategy-stratified subnetworks. Conclusions: The tightened response strategy contained reproduction of the virus, suppressed spatiotemporal clustering, and reshaped the networks of COVID-19 Omicron variant transmission. As such, PHSMs against Omicron are likely to benefit future responses as well.

Effectiveness of adenovirus type 5 vectored and inactivated COVID-19 vaccines against symptomatic COVID-19, COVID-19 pneumonia, and severe COVID-19 caused by the B.1.617.2 (Delta) variant: Evidence from an outbreak in Yunnan, China, 2021.

BACKGROUND: In partial response to the coronavirus disease 2019 (COVID-19) pandemic, countries around the world are conducting large-scale vaccination campaigns. Real-world estimates of vaccine effectiveness (VE) against the B.1.617.2 (Delta) variant are still limited. An outbreak in Ruili city of Chinaprovided an opportunity to evaluate VE against the Delta variant of two types of COVID-19 vaccines in use in China and globally - inactivated (CoronaVac and BBIBP-CorV) and adenovirus type 5 vectored (Convidecia) vaccines. METHODS: We estimated VE using a retrospective cohort study two months after the Ruili vaccination campaign (median: 63 days). Close contacts of infected people (Chinese nationality, 18 years and above) were included to assess VE against symptomatic Covid-19, COVID-19 pneumonia, and severe COVID-19. We calculated the relative risks (RR) of the outcomes for unvaccinated compared with fully vaccinated individuals. We used logistic regression analyses to estimate adjusted VEs, controlling for gender and age group (18-59 years and 60 years and over).We compared unvaccinated and fully vaccinated individuals on duration of RT-PCR positivity and Ct value. FINDINGS: There were 686 close contacts eligible for VE estimates. Adjusted VE ofad5-vectored vaccine was 61.5% (95% CI, 9.5-83.6) against symptomatic COVID-19, 67.9% (95%CI: 1.7-89.9) against pneumonia, and 100% (95%CI: 36.6-100) against severe/critical illness. For the two inactivated vaccines, combined VE was 74.6% (95% CI, 36.0-90.0) against symptomatic COVID-19, 76.7% (95% CI: 19.3-93.3) against pneumonia, and 100% (95% CI: 47.6-100) against severe/critical COVID-19. There were no statistically significant differences in VE between twoinactivated vaccines for symptomatic COVID-19 and for pneumonia, nor were there statistically significant differences between inactivated and ad5-vectored VE in any of the three outcomes. The median durations of RT-PCR positivity were 17 days for fifteen people vaccinated with an inactivated vaccine, 18 days for forty-four people vaccinated with the Ad5 vectored vaccine, and 26 days for eleven unvaccinated individuals. INTERPRETATION: These results provide reassuring evidence that the three vaccines are effective at preventing Delta-variant COVID-19 in short term following vaccination campaign, and are most effective at preventing more serious illness. The findings of reduced duration of RT-PCR positivity and length of hospital stay associated with full vaccination suggests potential saving of health-care system resources.

Economic and epidemiological evaluation of interventions to reduce the burden of hepatitis C in Yunnan province, China.

BACKGROUND: The paradigm shift in hepatitis C virus (HCV) treatment options in the last five years has raised the prospect of eliminating the disease as a global health threat. This will require a step-change in the number being treated with the new direct-acting antivirals (DAAs). Given constrained budgets and competing priorities, policy makers need information on how to scale-up access to HCV treatment. To inform such decisions, we examined the cost effectiveness of screening and treatment interventions in Yunnan, China. METHODS AND FINDINGS: We simulated the HCV epidemic using a previously published model of HCV transmission and disease progression, calibrated to Yunnan data, and implemented a range of treatment and screening interventions from 2019. We incorporated treatment, diagnosis, and medical costs (expressed in 2019 US Dollars, USD) to estimate the lifetime benefits and costs of interventions. Using this model, we asked: is introducing DAAs cost effective from a healthcare sector perspective; what is the optimal combination of screening interventions; and what is the societal return on investment of intervention? The incremental cost-effectiveness ratio (ICER) of switching to DAAs with a median cost of 7,400 USD (50,000 Chinese Yuan) per course is 500 USD/disability adjusted life year (DALY) averted; at a threshold of 50% of Yunnan gross domestic product (2,600 USD), switching to DAAs is cost effective 94% of the time. At this threshold, the optimal, cost-effective intervention comprises screening people who inject drugs, those in HIV care, men who have sex with men, and ensuring access to DAAs for all those newly diagnosed with HCV. For each USD invested in this intervention, there is an additional 0·80 USD (95% credible interval: 0·17-1·91) returned through reduced costs of disease or increased productivity. Returns on investment are lower (and potentially negative) if a sufficiently long-term horizon, encompassing the full stream of future benefits, is not adopted. The study had two key limitations: costing data were not always specific to Yunnan province but were taken from China-level studies; and modelled interventions may require more operational research to ensure they can be effectively and efficiently rolled-out to the entire province. CONCLUSIONS: Introducing DAAs is cost effective, the optimal package of screening measures is focussed on higher risk groups, and there are likely to be positive returns from investing in such HCV interventions. Our analysis shows that targeted investment in HCV interventions will have net benefits to society; these benefits will only increase as DAA costs fall.