Use of multiple recreational drugs is associated with new HIV infections among men who have sex with men in China: a multicenter cross-sectional survey.

BACKGROUND: There is limited information about the types of recreational drugs used by men who have sex with men (MSM) in China or the consequent impact on sexual health and human immunodeficiency virus (HIV) acquisition. METHODS: We recruited MSM from seven cities in China between 2012 and 2013 using multiple approaches including advertisements on gay websites, collaborating with local MSM community-based organizations, peer referrals, and venues such as gay bars and bathrooms visited by MSM. We divided participants into four subgroups based on the number of recreational drugs (RDs) used in the previous 6 months. We defined use of multiple RDs as use of ≥2 types of RDs. Demographics and HIV-related high-risk behaviors were collected, and blood samples were tested for recent HIV infection by the HIV-1 subtypes B, E, and D immunoglobulin G capture enzyme immunoassay (BED-CEIA). We used multivariable logistic regression adjusted for sociodemographics to determine the adjusted odds ratios (aORs) and associated 95% confidence intervals (CIs) of the subgroups of RD use for recent or established HIV infection. RESULTS: A total of 4496 Chinese MSM participated; 28.4% used RDs, and 5% used multiple types of RDs. The prevalence of each RD use was as follows: poppers (25.9%), ecstasy (2.4%), ketamine (1.2%), amphetamine (0.6%), tramadol (0.4%), methamphetamine (3.8%), and codeine (1.9%). Users of multiple RDs commonly used poppers combined with one or more other types of RDs. Multiple RD users were likely to be aged 26-30 years (vs. 18-25 and > 30 years), live in non-local cities (vs. local cities), never married (vs. married), have a high monthly income (vs. no income and 1-599 USD), use versatile positions during anal intercourse (vs. top or bottom), and have inadequate HIV-related prevention knowledge (vs. adequate). As the number of RDs used in the previous 6 months increased, the prevalence of HIV-related high-risk behaviors increased (P < 0.05 for all). The odds of recent HIV infection were higher among those who used one type (aOR = 2.2, 95% CI: 1.5-3.0) or two types of RD (aOR=2.3, 95% CI: 1.0-5.2) in the previous 6 months compared to the odds among those who did not use RDs. CONCLUSION: The level and pattern of multiple RD use among Chinese MSM were different from high-income countries. MSM who used more RDs are more likely to engage in high-risk sexual behaviors, and these behaviors may be associated with increases in new HIV infections.

Anonymous Linkage Between College Students and Human Immunodeficiency Virus (HIV) Facilities: Systematic Evaluation of Urine Self-Collection for HIV Testing Initiative in China.

BACKGROUND: Identifying young individuals living with human immunodeficiency virus (HIV) who are unaware of their status is a major challenge for HIV control in China. To address this, an innovative, anonymous vending machine-based urine self-collection for HIV testing (USCT) program was implemented in 2016 in colleges across China. METHODS: From June 2016 to December 2019, 146 vending machines stocked with urine self-collection kits were distributed on 73 college campuses across 11 provinces of China. Urine samples were collected, delivered, and tested in an anonymous manner. We analyzed the returned rate, reactive rate (likelihood of HIV screening positive), testing effectiveness (the annual number of college students living with HIV screened by USCT or other testing methods), and the spatiotemporal relationship between USCT usage and student activity per college generated from the usage of a social networking application. RESULTS: Among the 5178 kits sold, 3109 (60%) samples were returned; of these, 2933 (94%) were eligible for testing. The HIV reactive rate was 2.3% (66 of 2933). The average effectiveness ratio among the 34 participating Beijing colleges was 0.39 (12:31) between USCT and conventional testing methods. A strong spatiotemporal correlation between USCT numbers and online student activity was observed during school semesters in Beijing. CONCLUSIONS: USCT is a powerful complement to current interventions that target at-risk students and promote HIV testing. The social networking-based evaluation framework can be a guide in prioritizing at-risk target populations.

A risk signature with four autophagy-related genes for predicting survival of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a devastating brain tumour without effective treatment. Recent studies have shown that autophagy is a promising therapeutic strategy for GBM. Therefore, it is necessary to identify novel biomarkers associated with autophagy in GBM. In this study, we downloaded autophagy-related genes from Human Autophagy Database (HADb) and Gene Set Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to identify genes for constructing a risk signature. A nomogram was developed by integrating the risk signature with clinicopathological factors. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were used to evaluate the efficiency of the prognostic model. Finally, four autophagy-related genes (DIRAS3, LGALS8, MAPK8 and STAM) were identified and were used for constructing a risk signature, which proved to be an independent risk factor for GBM patients. Furthermore, a nomogram was developed based on the risk signature and clinicopathological factors (IDH1 status, age and history of radiotherapy or chemotherapy). ROC curve and calibration plot suggested the nomogram could accurately predict 1-, 3- and 5-year survival rate of GBM patients. For function analysis, the risk signature was associated with apoptosis, necrosis, immunity, inflammation response and MAPK signalling pathway. In conclusion, the risk signature with 4 autophagy-related genes could serve as an independent prognostic factor for GBM patients. Moreover, we developed a nomogram based on the risk signature and clinical traits which was validated to perform better for predicting 1-, 3- and 5-year survival rate of GBM.

Identification of a Five-Pseudogene Signature for Predicting Survival and Its ceRNA Network in Glioma.

Background: Glioma is the most common primary brain tumor with a dismal prognosis. It is urgent to develop novel molecular biomarkers and conform to individualized schemes. Methods: Differentially expressed pseudogenes between low grade glioma (LGG) and glioblastoma multiforme (GBM) were identified in the training cohort. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox proportional hazards regression analyses were used to select pseudogenes associated with prognosis of glioma. A risk signature was constructed based on the selected pseudogenes for predicting the survival of glioma patients. A pseudogene-miRNA-mRNA regulatory network was established and visualized using Cytoscape 3.5.1. Gene Oncology (GO) and signaling pathway analyses were performed on the targeted genes to investigate functional roles of the risk signature. Results: Five pseudogenes (ANXA2P2, EEF1A1P9, FER1L4, HILS1, and RAET1K) correlating with glioma survival were selected and used to establish a risk signature. Time-dependent receiver operating characteristic (ROC) curves revealed that the risk signature could accurately predict the 1, 3, and 5-year survival of glioma patients. GO and signaling pathway analyses showed that the risk signature was involved in regulation of proliferation, migration, angiogenesis, and apoptosis in glioma. Conclusions: In this study, a risk signature with five pseudogenes was constructed and shown to accurately predict 1-, 3-, and 5-year survival for glioma patient. The risk signature may serve as a potential target against glioma.

A Risk Classification System With Five-Gene for Survival Prediction of Glioblastoma Patients.

Objective: Glioblastoma (GBM) is the most common and fatal primary brain tumor in adults. It is necessary to identify novel and effective biomarkers or risk signatures for GBM patients. Methods: Differentially expressed genes (DEGs) between GBM and low-grade glioma (LGG) in TCGA samples were screened out and weight correlation network analysis (WGCNA) was performed to confirm WHO grade-related genes. Five genes were selected via multivariate Cox proportional hazards regression analysis and were used to construct a risk signature. A nomogram composed of the risk signature and clinical characters (age, radiotherapy, and chemotherapy experience) was established to predict 1, 3, 5-year survival rate for GBM patients. Results: One hundred ninety-four DEGs in blue gene module were found to be positively related to WHO grade via WGCNA. Five genes (DES, RANBP17, CLEC5A, HOXC11, POSTN) were selected to construct a risk signature for GBM via R language. This risk signature was identified to independently predict the outcome of GBM patients, as well as stratified by IDH1 status, MGMT promoter status, and radio-chemotherapy. The nomogram was established which combined the risk signature with clinical factors. The results of c-index, ROC curve and calibration plot revealed the nomogram showing a good accuracy for predicting 1, 3, or 5-year survival of GBM patients. Conclusion: The risk signature with five genes could serve as an independent factor for predicting the prognosis of patients with GBM. Moreover, the nomogram with the risk signature and clinical traits proved to perform better for predicting 1, 3, 5-year survival rate.

ARL3 is downregulated and acts as a prognostic biomarker in glioma.

BACKGROUND: Glioma is the most common primary malignant brain tumor in adults with a poor prognosis. ARL3 is a member of the ARF family, and plays a key role in ciliary function and lipid-modified protein trafficking. ARL3 has been reported to be involved in ciliary diseases, in which it affects kidney and photoreceptor development. However, the functional role of ARL3 in cancer remains unknown. In this study, we aimed to explore ARL3 expression and its roles in glioma prognosis. METHODS: RT-PCR and immunohistochemistry were performed to examine the expression level of ARL3 in glioma samples. Data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Repository for Molecular Brain Neoplasia Data (REMBRANDT) databases were employed to investigate ARL3 expression and its roles in glioma prognosis. A nomogram for predicting 3- or 5-year survival was established using Cox proportional hazards regression. Finally, gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were performed to explore the biological function. RESULTS: ARL3 expression was downregulated in glioma, and associated with poor prognosis in glioma patients. The C-indexes, areas under the ROC curve and calibration plots of the nomogram indicated an effective predictive performance for glioma patients. In addition, GO and pathway analyses suggested the involvement of ARL3 in angiogenesis and immune cell infiltration in the microenvironment. CONCLUSIONS: Low ARL3 expression predicted poor prognosis and contributed to antiangiogenesis and the proportion of infiltrating immune cells in the GBM microenvironment. Thus, ARL3 may be a prognostic marker and therapeutic target for glioma.

Correlates of HIV infection among transgender women in two Chinese cities.

BACKGROUND: In an era when HIV transmission has been on the rise among men who have sex with men (MSM), transgender women may play a considerable role in China's current HIV epidemic as a potential "bridge" of HIV transmission between homosexual and heterosexual populations. We sought to understand the risk behaviours and factors associated with HIV infection among transgender women in two cities in China. METHODS: From January to December 2016, we recruited transgender women with the help of community-based organizations (CBOs) through a wide range of methods, including snowball sampling. After recruitment, we asked participants to fill out a structured questionnaire including questions about socio-demographics, sexual behaviours, condom use, substance use and uptake of health care services. HIV infection status was determined by using two different rapid testing reagents. RESULTS: Among 498 subjects enrolled in this study, 233 were from Shanghai and 265 were from Tianjin. The median age was 30 years (range: 18-68; IQR: 24-33). Of them, 337 (67.7%) preferred feminine dress, 13 (2.6%) had undergone transsexual operation and 68 (13.7%) had used hormones for transition purposes. Nearly half (45.6%) reported having regular partners, and 351 (70.5%) had casual partners. Regarding condom use, 81.5% reported not always using condoms with stable partners, and 70.9% reported not using condoms with casual partners. Twenty-five (5.0%) had a history of buying sex and fifty-one (10.2%) had a history of selling sex in the past three months. A total of 200 (40.2%) participants had used at least one kind of controlled substance in the past six months. The most commonly used substances were amyl nitrates (rush popper) (99.5%) and 5-MeO-DiPT (20.0%). Among rush popper users, 170 (85.4%) reported always having sex while on the drug, and 177 (88.9%) reported increased sexual pleasure after using the drug. The HIV infection risk factors identified in our study were being located in Shanghai (aOR = 9.35, 95% CI = 3.89-22.49), selling sex in the past three months (aOR = 3.44, 95% CI = 1.31-9.01), and substance use in the past six months (aOR = 5.71, 95% CI = 2.63-12.41). CONCLUSIONS: Transgender women bear a high HIV burden in the two Chinese cities. Those involved in commercial sex tended to have inconsistent condom use, leading to high risk of HIV infection. Substance use was an independent risk factor of HIV infection by increasing sexual activities and unprotected sex, which indicated an aggravated and complex situation with possible interacting syndemic factors that could cumulatively facilitate sexual risk behaviours and HIV infection in transgender women. There is an urgent need for innovative and appropriate HIV prevention programmes targeting this unique population. Efforts should be made to provide them with tailored services including persuasive communication on consistent condom use, substance use counselling and related referral services, all with the goal of reducing HIV epidemic among transgender women.

HIV and syphilis epidemic among MSM and non-MSM aged 50 and above in Shanghai, China: A yearly cross-sectional study, 2008-2014.

The magnitude of the HIV and syphilis epidemic among Chinese men ages 50 and older is unclear. In this study, we aimed to characterise and compare the prevalence of HIV and syphilis infections; linkage to care among those infected with HIV; and the geographic distribution of the two epidemics among elderly men who have sex with men (MSM) and non-MSM in Shanghai, China. This cross-sectional study involved 12,910 men ages 50 and above who participated in the HIV voluntary and counselling testing programme each year from 2008 to 2014. HIV prevalence among MSM in our sample ranged between 4.9% and 15.4%, while syphilis frequency among non-MSM decreased from 26.0% to 18.7%. Further, in 2014, MSM participants had a higher HIV prevalence than non-MSM (4.9% vs 1.8%), whereas syphilis was higher in older non-MSM compared to MSM (18.7% vs 12.4%). Among those infected with HIV, 121/211 (53.75%) of participants were linked to HIV treatment, where the linkage rate was comparable to that in Kunming [Zhao, S., Zhao, G., Zhang, W., liao, B., Chu C., Wang J., & Li, L. (2015). Compare the difference of efficiency between voluntary counseling testing and provider-initiated testing counseling for identifying HIV/AIDS in Kunming. Chinese Journal of AIDS & STD, 21(7), 623-625]. The high burden of HIV and syphilis among men ages 50 and older in Shanghai, China highlights the need to target older Chinese men, both MSM and non-MSM, with prevention efforts.

High-risk behaviour and HIV infection risk among non-local men who have sex with men with less than a single year's residence in urban centres: a multicentre cross-sectional study from China.

OBJECTIVES: Traditionally, subjects' migration status has usually been defined on the basis of their registered residency status. We attempted to redefine migration based on the duration of residency in their cities of migration and to explore more precisely the impact of migration on HIV infection risk in men who have sex with men (MSM). METHODS: A multisite cross-sectional study was conducted during 2012-2013 in seven Chinese cities. Questionnaire surveys were conducted and blood was drawn to test for antibodies to HIV, syphilis and herpes simplex virus-2 (HSV-2). MSM who were unregistered local residents and had resided in their cities of migration for ≤1 or >1 year were defined as migrant MSM, or transitional MSM, respectively. RESULTS: Compared with transitional MSM and local MSM, migrant MSM had poorer HIV knowledge and higher rates of high-risk behaviour, including earlier sexual debut, multiple sexual partners, participation in commercial sex and recreational drug use. Multivariate logistic regression analysis showed that HIV prevalence among migrant MSM was higher than local MSM (p<0.05). This relationship, however, did not hold for transitional MSM and local MSM (p>0.05). Male sex work, recreational drug use, syphilis infection and HSV-2 infection were independently associated with HIV infection among migrant MSM. CONCLUSIONS: Non-local MSM with shorter residence were at greater risk of HIV acquisition. More focus should be placed on HIV behavioural interventions targeting non-local MSM with temporary residence.

Treatment-seeking behaviour and barriers to service access for sexually transmitted diseases among men who have sex with men in China: a multicentre cross-sectional survey.

BACKGROUND: Delayed or inappropriate treatment for sexually transmitted diseases (STDs) increases the risk of HIV acquisition and may cause other harmful outcomes. However, studies on STD treatment-seeking behaviour and correlated factors in men who have sex with men (MSM) are scarce. This information is crucial for the promotion of STD treatment-seeking behaviour and reduction of HIV transmission among Chinese MSM. METHODS: During 2012-2013, a multicentre cross-sectional study was conducted in 7 Chinese cities. Participants completed an interview-questionnaire and gave venous blood samples, which were then tested for antibodies to HIV, syphilis, and herpes simplex virus-2 (HSV-2). MSM who tested positive for syphilis/HSV-2 or had obvious STD-related symptoms within the last 12 months were defined as suspected STD-infected MSM. RESULTS: Of the 4 496 eligible MSM who completed this survey, 24.4% (1 096/4 496) were categorized as suspected STD-infected MSM. 35.7% (391/1 096) of these MSM with suspected STD infections sought STD treatment in clinics within the last 12 months. Among MSM who did not attend STD clinics for treatment, the prevalence of syphilis and HSV-2 was significantly higher; the HIV prevalence and incidence within this subpopulation reached as high as 14.5% and 12.2/100 person-years, respectively. Multivariate logistic regression analysis indicated that having 7-12 years of education (vs. ≤6 years; aOR, 2.5; 95%CI, 1.0-6.1), ≥13 years of education (vs. ≤6 years: aOR, 2.8; 95%CI, 1.2-7.0), monthly income >500 USD (vs. ≤500 USD: aOR, 1.5; 95%CI, 1.1-2.1), obvious STD-related symptoms within last 12 months (aOR, 5.3; 95%CI, 3.7-7.5), being HIV infected (aOR, 1.7; 95%CI, 1.1-2.6), currently syphilis infected (aOR, 0.6; 95%CI, 0.4-0.9) and HSV-2 infected (aOR, 0.6; 95%CI, 0.5-0.9) were independent correlates with seeking STD treatment in clinics among Chinese MSM. CONCLUSIONS: The high prevalence of STD infection coupled with a low proportion of individuals who exhibit appropriate treatment-seeking behaviour create a high risk of a growing HIV epidemic among Chinese MSM. Models that prioritize better screening for and education about STDs should be urgently implemented, especially among low-income MSM.

Enhancing HIV Testing and Treatment among Men Who Have Sex with Men in China: A Pilot Model with Two-Rapid Tests, Single Blood Draw Session, and Intensified Case Management in Six Cities in 2013.

OBJECTIVES: To explore models to improve HIV testing, linkage to care and treatment among men who have sex with men (MSM) in cooperation with community-based organizations (CBOs) in China. METHODS: We introduced a new model for HIV testing services targeting MSM in six cities in 2013.These models introduced provision of rapid HIV testing by CBO staff and streamlined processes for HIV screening, confirmation of initial reactive screening results, and linkage to care among diagnosed people. We monitored attrition along each step of the continuum of care from screening to treatment and compared program performance between 2012 and 2013. According to the providers of two rapid tests (HIV screening), four different services delivery models were examined in 2013: Model A = first screen at CDC, second at CDC (Model A = CDC+CDC), Model B = first and second screens at CBOs (Model B = CBO+CBO), Model C = first screen at CBO, second at Hospital (Model C = CBO+Hosp), and Model D = first screen at CBO, second at CDC (Model D = CBO+CDC). Logistic regressions were performed to assess advantages of different screening models of case finding and case management. RESULTS: Compared to 2012, the number of HIV screening tests performed for MSM increased 35.8% in 2013 (72,577 in 2013 vs. 53,455 in 2012). We observed a 5.6% increase in proportion of cases screened reactive receiving HIV confirmatory tests (93.9% in 2013 vs. 89.2% in 2012, χ2 = 48.52, p<0.001) and 65% reduction in loss to CD4 cell count tests (15% in 2013 vs. 43% in 2012, χ2 = 628.85, p<0.001). Regarding linkage to care and treatment, the 2013 pilot showed that the Model D had the highest rate of loss between screening reactive and confirmatory test among the four models, with 18.1% fewer receiving a second screening test and a further 5.9% loss among those receiving HIV confirmatory tests. The Model B and the Model C showed lower losses (0.8% and 1.3%) for newly diagnosed HIV positives receiving CD4 cell count tests, and higher rates of HIV positives referred to designated ART hospitals (88.0% and 93.3%) than the Model A and Model D (4.6% and 5.7% for CD4 cell count test, and 68.9% and 64.4% for referring to designated ART hospitals). The proportion of cases where the screening test was reactive that were commenced on ART was highest in Model C; 52.8% of cases commenced on ART compared to 38.9%, 34.2% and 21.1% in Models A, B and D respectively. Using Model A as a reference group, the multivariate logistic regression results also showed the advantages of Models B, C and D, which increased CD4 cell count test, referral to designated ART hospitals and initiation of ART, when controlling for program city and other factors. CONCLUSIONS: This study has demonstrated that involvement of CBOs in HIV rapid testing provision, streamlining testing and care procedures and early hospital case management can improve testing, linkage to, and retention in care and treatment among MSM in China.

Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China.

To explore the evolutionary dynamics and molecular transmission patterns of HIV-1 CRF01_AE in depth among men who have sex with men (MSM) in Shanghai, we constructed phylogenetic tree and genetic transmission networks based on 1, 152 pol sequences from MSM, 282 from other risk groups and 795 references. Phylogenetic analyses identified two distinct major CRF01_AE lineages and a Shanghai-based sub-lineage. The estimated tMRCAs for lineage 1 and 2 were 1996.0 (1992.9-1999.2) and 1997.8 (1994.3-2001.4), respectively. Of the 1, 152 MSM, 681 (59.1%) were identified as belonging to 241 separate networks. Of these 681 individuals in networks, 74.2% were linked to cases diagnosed in different years, 4.3% were linked to heterosexual women, and 0.7% were linked to persons who inject drugs. A total of 71 networks including 180 individuals diagnosed in Shanghai with the same domicile were found. Recent infection (P = 0.022) and sampling year after 2011 (P < 0.001) were significantly associated with potential transmission links among the networks. Besides, a significant transmission of viruses with drug resistant mutations at V179D/E were found in the networks. Given these findings, we propose that genetic transmission analysis is a useful tool in HIV intervention strategies to curb the spread of virus and promoting public health.

High HIV incidence epidemic among men who have sex with men in china: results from a multi-site cross-sectional study.

BACKGROUND: Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, timely and comprehensive investigation. METHODS: Mixed methods were used to recruit MSM from seven cities in China between 2012 and 2013. Recent and established HIV infections were estimated by Western Blot and BED HIV-1 capture enzyme immunoassay. Syphilis and herpes simplex virus-2 (HSV-2) were also tested. RESULTS: A total of 4496 eligible MSM were recruited. The majority was aged ≤35 years (77.5 %), migrants (60.3 %), never married (69.8 %), and played receptive role in anal sex (70.5 %). The HIV prevalence was 9.9 %, and 41.9 % were recently infected, with sensitivity/specificity adjusted HIV incidence of 8.9 (95 % CI: 7.6-10.2)/100 Person-Years. The prevalence of history HSV-2 and syphilis were 12.5 % and 8.5 %, respectively. Recent HIV infection was associated with having multiple male partners (aOR = 1.4, 95 % CI 1.1-1.9), recreational drug use (aOR = 2.2, 95 % CI 1.6-3.0), anal bleeding (aOR = 2.1, 95 % CI 1.4-3.0), syphilis infection (aOR = 2.8, 95 % CI 1.9-4.3) and history HSV-2 infection (aOR = 2.3, 95 % CI 1.5-3.3). CONCLUSION: High rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having multiple partners, history of recreational drug use and syphilis or HSV-2 infection seemed to be the need of the hour.

Decreasing age at first anal intercourse among men who have sex with men in China: a multicentre cross-sectional survey.

INTRODUCTION: Literature on the age at first anal intercourse (AFAI) among men who have sex with men (MSM) is limited. We aimed to elucidate the evolution of AFAI and the factors associated with early AFAI, based on a large sample of MSM in China. METHODS: We collected information on the demographics and sexual behaviours of MSM from seven large cities in China from 2012 to 2013. Blood samples were collected for HIV serology. AFAI was calculated for MSM born in different time periods. Linear regression models were used to explore factors associated with younger AFAI. RESULTS: A total of 4491 MSM (median age: 27 years, median AFAI: 21 years) were recruited. Median AFAI decreased steadily from 33 years of age among MSM born from 1940 to 1959 to 18 years of age among MSM born from 1990 to 1996. Factors significantly associated with younger AFAI included more recent birth cohort, being unmarried or living with a male partner, being a student or industry worker, the gender of the first partner being male, and using Rush or Ecstasy in the past six months (p for all <0.05). CONCLUSIONS: AFAI among MSM in China has considerably decreased over the past few decades. The decreasing AFAI and factors associated with younger AFAI point to the necessity of early sex education and control of recreational drug use among MSM in China.

A Large-scale Survey of CRF55_01B from Men-Who-Have-Sex-with-Men in China: implying the Evolutionary History and Public Health Impact.

The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China, involving the co-circulation of several different lineages of HIV-1 strains, including subtype B and CRF01_AE. This expansion has created conditions that facilitate the generation of new recombinant strains. A molecular epidemiologic survey among MSM in 11 provinces/cities around China was conducted from 2008 to 2013. Based on pol nucleotide sequences, a total of 19 strains (1.95%) belonged to the CRF55_01B were identified from 975 MSM in 7 provinces, with the prevalence range from 1.5% to 12.5%. Near full length genome (NFLG) sequences from six epidemiologically-unlinked MSM were amplified for analyzing evolutionary history, an identical genome structure composed of CRF01_AE and subtype B with four unique recombination breakpoints in the pol region were identified. Bayesian molecular clock analyses for both CRF01_AE and B segments indicated that the estimated time of the most recent common ancestors of CRF55_01B was around the year 2000. Our study found CRF55_01B has spread throughout the most provinces with high HIV-1 prevalence and highlights the importance of continual surveillance of dynamic changes in HIV-1 strains, the emergence of new recombinants, and the need for implementing effective prevention measures specifically targeting the MSM population in China.

HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai, China.

The HIV-1 epidemic among men who have sex with men (MSM) has been spreading throughout China. Shanghai, a central gathering place for MSM, is facing a continuously increasing incidence of HIV-1 infection. In order to better understand the dynamics of HIV-1 diversity and its influence on patient's immune status at baseline on diagnosis, 1265 newly HIV-1-infected MSM collected from January 2009 to December 2013 in Shanghai were retrospectively analyzed for genetic subtyping, CD4+T cell counts, and viral loads. HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (62.13%), CRF07_BC (24.51%), subtype B (8.06%), CRF55_01B (3.24%), CER67_01B (0.95%), CRF68_01B (0.4%), CRF08_BC (0.08%) and CRF59_01B (0.08%). Twenty-four unique recombination forms (URFs) (1.98%) were identified as well. Bayesian inference analysis indicated that the introduction of CRF01_AE strain (1997) was earlier than CRF07_BC strain (2001) into MSM population in Shanghai based on the time of the most recent common ancestor (tMRCA). Three epidemic clusters and five sub-clusters were found in CRF01_AE. Significantly lower CD4+T cell count was found in individuals infected with CRF01_AE than in those infected with CRF07_BC infection (P<0.01), whereas viral load was significantly higher those infected with CRF01_AE than with CRF07_BC (P<0.01). In addition, the patients with >45 years of age were found to have lower CD4+T cell counts and higher viral loads than the patients with <25 years of age (P<0.05). This study reveals the presence of HIV-1 subtype diversity in Shanghai and its remarkable influence on clinical outcome. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster, patient's baseline CD4+T cell count and viral load would be of great value to monitoring of disease progression, intervention for transmission, improvement of antiretroviral therapy strategy and design of vaccines.

Increase of RT-related transmitted drug resistance in non-CRF01_AE among HIV type 1-infected men who have sex with men in the 7 cities of China.

OBJECTIVES: To elucidate new features in the prevalence of HIV-1 transmitted drug resistance (TDR) in men who have sex with men (MSM) in China. METHODS: A total of 441 HIV-1-positive subjects were recruited from high-risk MSM populations in 7 cities across China between 2012 and 2013. Nucleotide sequences of 1.1-kb pol-RT regions were amplified and sequenced from 367 of the 441 samples. Phylogenetic and genetic drug-resistant analyses were performed. RESULTS: The overall distribution of HIV-1 genotypes was as the following: CRF01_AE, 52.3%; CRF07_BC, 33.2%; 01/B recombinants, 6.0%; subtype B (United States-European), 3.8%; subtype B', 3.8%; and CRF08_BC, 0.8%. About 91.3% of the sequences clustered together. An overall 4.6% TDR rate was found. Reverse transcriptase (RT)-related TDR reached 2.7%. TDR of 2.2% was detected in protease region. Most of RT-related TDRs were detected in non-CRF01_AE subtypes (90.0%, 9/10), including T215A/S, K101E, K103N, V106M, and E138G. Most of the strains with TDRs (88.2%, 15/17) were presented in the clusters. TDR strains against non-nucleoside reverse transcriptase inhibitors in non-CRF01_AE subtypes also formed some subclusters (70.0%, 7/10). One CRF07_BC subject with K103N in Kunming had a very close genetic distance with one that received highly active antiretroviral therapy locally (bootstrap = 99%). Two CRF55_01B subjects carrying K103N in Changsha and Nanjing also had a very close genetic distance (bootstrap = 100%). CONCLUSIONS: RT-related TDR of non-CRF01_AE became the main TDR among MSM in China. There is an increasing trend and a potential transmission risk for the RT-related TDR among MSM throughout China. Some TDRs could have already been transmitted among different cities. Intervention efforts should be strengthened among MSM to prevent further transmission of HIV and the proliferation of the strains with TDR.

Recreational drug use and risks of HIV and sexually transmitted infections among Chinese men who have sex with men: Mediation through multiple sexual partnerships.

BACKGROUND: Recreational drug use (RDU) may result in sexual disinhibition and higher risk for HIV and other sexually transmitted infections (STIs) among men who have sex with men (MSM) in China. We assessed whether RDU was associated with HIV, syphilis, and herpes simplex virus type 2 (HSV-2) within the context of multiple sexual partnerships and unprotected sex. METHODS: We conducted a cross-sectional study among sexually-active MSM in six Chinese cities (Kunming, Jinan, Changsha, Zhengzhou, Nanjing, and Shanghai) in 2012-2013. We interviewed participants regarding RDU and sexual activity and drew blood for HIV, syphilis, and HSV-2. We fit multiple logistic regression models to assess associations of drug use and HIV, syphilis and HSV-2 infections, controlling for number of sexual partners and unprotected sex. RESULTS: Of 3830 participants, 28% reported ever using ≥1 of these drugs in the past 6 months: popper (alkyl nitrites), ecstasy, ice (methamphetamine), amphetamine, tramadol, and ketamine. In the past six months, 62% of MSM reported ≥2 sexual partners and 76% did not use condoms at last sexual encounter. HIV, syphilis and HSV-2 prevalences were 9.2%, 12.2%, and 10.3%, respectively.RDU was associated with HIV infection (aOR = 1.67; 95% CI, 1.31-2.13). Men with RDU were more likely to report multiple sexual partners (OR = 1.69; 95% CI, 1.44-1.98) and unprotected sex (aOR = 1.25; 95% CI, 1.05-1.49). The RDU-HIV association persisted (aOR = 1.58; 95% CI = 1.23-2.02) after adjusting for numbers of partners. CONCLUSIONS: RDU was associated with multiple sexual partnerships, unprotected sex, and HIV among Chinese MSM. It is plausible that RDU is a driver of increased sexual/HIV risk and/or may be an associated behavior with sexually risky lifestyles. Community engagement is needed.

Identification and characterization of a novel HIV-1 circulating recombinant form (CRF59_01B) identified among men-who-have-sex-with-men in China.

The HIV-1 epidemic among men-who-have-sex-with-men (MSM) continues to expand in China. A large-scale national survey we conducted on HIV-1 strains among MSM in 11 provinces in China from 2008 to 2013 (n = 920) identified a novel transmission cluster consisting of six strains (0.7%) that belonged to a new circulating recombinant form (designated CRF59_01B). CRF59_01B contains two subtype B segments of U.S.-European origin (in the pol and vpu-env regions) in a CRF01_AE backbone. CRF59_01B is the second CRF (after CRF55_01B) circulating primarily among MSM in China. CRF59_01B occurs at a low frequency (less than 1%), but it was detected in four different provinces/regions in China: Liaoning (northeast China) (n = 3); Hunan (central China) (n = 1); Guangdong (south China) (n = 1); Yunnan (southwest China) (n = 1). One additional recombinant strain was detected in a heterosexual individual in Liaoning province but is not the focus of this paper. Bayesian molecular clock analyses indicate that CRF59_01B emerged as a result of recombination between CRF01_AE and subtype B around the year 2001. The emergence of multiple forms of recombinants and CRFs reflects the ever-increasing contribution of homosexual transmission in China's HIV epidemic and indicates an active HIV transmission network among MSM in China.

Evidence that HIV-1 CRF01_AE is associated with low CD4+T cell count and CXCR4 co-receptor usage in recently infected young men who have sex with men (MSM) in Shanghai, China.

Men who have sex with men (MSM) have recently accounted for an alarmingly increasing proportion of HIV-1 transmission in China. In order to investigate the immune status as a result of CRF01_AE infection and CXCR4 co-receptor usage in a young Shanghai-based HIV-1-infected MSM population in Shanghai, 364 HIV-1-infected MSM with average age of 22.7 years old, newly diagnosed between Jan 2009 and Jul 2013 were analyzed for CD4+T cell count, subtyping using phylogenetic analysis, and viral co-receptor tropism using Geno2pheno and webPSSM in combination. A total of 276 individuals were identified as recently infected. Subtype assignment were as follows: 176 (63.8%) CRF01_AE, 77 (27.9%) CRF07_BC, and 23 (8.3%) subtype B. Besides, 24 second-generation recombinant strains were identified. A lower CD4+T cell count at baseline survey was observed among CRF01_AE strain-infected individuals, compared to those who were infected with CRF07_BC (P<0.01). The frequency of baseline CD4+T cell count <200 was higher and the frequency of CD4 T counts >500 lower in CRF01_AE infection than CRF07_BC infection. It is worth noting that 32.4%-40.9% of CRF01_AE strain-infected individuals were predicted to carry CXCR4-tropic viruses whereas none of CRF07_BC and subtype B were found to be as CXCR4-tropic viruses (P<0.001). As could be expected CXCR4 tropism was associated with lower CD4 T counts. This study revealed that CRF01_AE strains with high frequency of CXCR4 tropism are prevailing in the young MSM population in China and could potentially cause a severe loss of CD4+T cell count and rapid disease progression. A regular surveillance of HIV-1 subtypes, CD4+T cell count and viral co-receptor usage would be greatly beneficial for effectively monitoring disease progression, improvement of antiretroviral therapy strategy and prompt intervention of transmission.