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1.  Identification of a Novel HIV-1 Second-Generation Recombinant Form (CRF01_AE/CRF07_BC) in Jilin, China 
Abstract
We report here a novel HIV-1 second-generation recombinant form (CRF01_AE/CRF07_BC) isolated from an HIV-positive male subject infected through heterosexual contact in Jilin province in northeastern China. Phylogenic analysis shows that this novel second-generation recombinant (JL.RF09) was composed of two well-established circulating recombinant forms (CRF01_AE and CRF07_BC), with two recombinant breakpoints observed in the vpu/env and env gene regions, respectively. The CRF01_AE region of the recombinant was clustered together with a previously described subcluster 4a lineage of CRF01_AE, which is exclusively circulating among men who have sex with men (MSM) in northern China, indicating that the parental origin of the CRF01_AE region in JL.RF09 was from MSM in north China. The CRF07_BC regions of the recombinant are clustered within the CRF07_BC cluster but are distinct from other CRF07_BC references. The detailed origin of CRF07_BC in this recombinant is still not clear. The emergence of the novel HIV-1 recombinant indicates the ongoing generation of recombinants involving CRF01_AE and CRF07_BC, and may provide vital insights into our understanding of the dynamics and complexity of the HIV-1 epidemic in China.
doi:10.1089/aid.2014.0071
PMCID: PMC4118697  PMID: 24892359
2.  The sexually driven epidemic in youths in China’s southwestern border region was caused by dynamic emerging multiple recombinant HIV-1 strains 
Scientific Reports  2015;5:11323.
Dehong prefecture, Yunnan province on China’s southwestern border was the gateway of the country’s AIDS epidemic. Studies on HIV-1 molecular epidemiology will provide key information on virus transmission dynamics and help to inform HIV prevention strategies. HIV-1 infected youths (age 16–25 years) diagnosed in the continuous 3 months in 2009 to 2012 were enrolled. By means of phylogenetic and statistical analyses, It was showed that two thirds (133/205) of youths in Dehong, of which 74.1% were infected sexually, were infected by uncharacterized recombinant HIV-1 strains. Among them about 59.4% (79/131) were unique recombinant forms (URFs) and 40.6% (54/131) formed 11 transmission clusters, termed potential circulating recombinant forms (pCRFs). The emergence of recombinants was statistically significant related with people of low education, residents outside the capital city of Dehong and being Myanmar residents. It was the first report with ongoing HIV-1 recombinant strains in a sexually driven epidemic area in China. Great efforts should be put on reducing multiple risk exposures behavior in local young people, containing the spread of pCRFs to other regions, and preventing the URFs from evolving into future CRFs. Collaborative prevention across border is needed to better control the local AIDS epidemic.
doi:10.1038/srep11323
PMCID: PMC4489098  PMID: 26133091
3.  Near Full-Length Genome Sequence of a Novel HIV-1 Recombinant Form (CRF01_AE/B) Detected Among Men Who Have Sex with Men in Jilin Province, China 
Abstract
We report here a novel HIV-1 recombinant form (CRF01_AE/B) detected from a comprehensive HIV-1 molecular epidemiologic study among men who have sex with men (MSM) in Jilin province of northeastern China. The near full-length genome (NFLG) analyses showed that the novel HIV-1 recombinant isolate (JL.RF07) was composed of CRF01_AE cluster 5 (northeastern China origin) and subtype B (U.S. and European origin), with six recombinant breakpoints observed in the pol, vif, tat, rev, and env gene regions. To the best of our knowledge, this is the first detection of a novel HIV-1 recombinant form (CRF01_AE/B) in Jilin, which may indicate an active transmission network of HIV-1 infection among MSM in the region. Further studies of the molecular epidemiology of the HIV-1 epidemic among MSM in northeastern China are necessary to gain a fuller understanding of the transmission network and potential public health impact of HIV-1 among MSM in this region.
doi:10.1089/aid.2014.0008
PMCID: PMC4076975  PMID: 24521207
4.  Near Full-Length Genome Identification of a Novel HIV-1 Recombinant Form (CRF01_AE/B′/C) Among Heterosexuals in Jilin, China 
Abstract
Recombinant forms contribute significantly to the genetic diversity of HIV-1. Here we report a novel HIV-1 recombinant form (CRF01_AE/B′/C) detected from a comprehensive HIV-1 molecular epidemiologic study among heterosexuals in Jilin province of northeastern China. Recombinant analyses of the near full-length genome (NFLG) of the novel HIV-1 recombinant isolate (JL.RF01) showed that the backbone of the genome was CRF01_AE, and three insertions of subtype B′ (242, 370, and 233 bp) and C (1142, 230, and 271 bp), respectively, were inserted along the genome. Phylogenetic analyses revealed that the novel HIV-1 recombinant form (CRF01_AE/B′/C) more likely originated from Thailand subtype B′ and CRF01_AE and India subtype C. We report a unique mosaic structure that is distinct to HIV-1 CRF01_AE/B′/C recombinant viruses reported to date. The emergence of this novel recombinant form (CRF01_AE/B′/C) suggests the increasing significance of heterosexual transmission contributing to the complexity of the HIV-1 epidemic in northeastern China.
doi:10.1089/aid.2013.0278
PMCID: PMC4076986  PMID: 24446780
5.  Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection 
Cellular and Molecular Immunology  2014;12(4):435-443.
Increased levels of monocyte–platelet aggregates (MPAs) are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-1-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 (PSGL-1) was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-1.
doi:10.1038/cmi.2014.66
PMCID: PMC4496539  PMID: 25109683
HIV-1; immune activation; monocytes; platelets; sCD163
6.  Identification of a Novel HIV Type 1 Circulating Recombinant Form (CRF65_cpx) Composed of CRF01_AE and Subtypes B and C in Western Yunnan, China 
Abstract
A novel HIV-1 circulating recombinant form (CRF) designated CRF65_cpx was recently characterized from three epidemiologically unlinked individuals infected through heterosexual contact in western Yunnan province of China. This is the first complex mosaic HIV-1 CRF, consisting of contributions from three or more different subtypes, identified in China. An additional full-length genome sequence with identical recombinant breakpoints was found among a previously reported recombinant strain from a man who had sex with a man in Anhui province of East Central China. The breakpoint analysis of the recombinants showed a complex genome organization composed of parental subtypes B′ (Thailand variant of subtype B), C, and CRF01_AE, with 13 recombination breakpoints observed in almost all structure genes of HIV-1. The generation of complex recombinant forms is likely due to cocirculation of multiple lineages of HIV-1 strains in high-risk populations in western Yunnan.
doi:10.1089/aid.2013.0233
PMCID: PMC4046203  PMID: 24279591
7.  Sexual partnerships with men and women among men who have sex with men in Beijing and Chongqing, China, 2010 
AIDS and behavior  2014;18(1):180-188.
HIV is spreading among Chinese MSM and may possibly lead to infection of female partner. Pressure to marry may drive a greater proportion of Chinese MSM to have female partners than MSM elsewhere in the world. Measurement of the size of the potential risk to female partners of Chinese MSM is inconsistent in literature. From samples of MSM in two Chinese cities, we documented numbers of sexual partners and sexual activity with those partners. About 500 MSM were sampled in each city. 11.0% and 12.6% of men reported having any female partners in the past six months in Chongqing and Beijing, respectively. Men also reported that only 7.3% and 6.7% of their entire partnerships were with women in Chongqing and Beijing, respectively. Defining transmission risk accounting for receptive anal sex among men and condom non-use with both male and female partners 3.4% of MSM in both Chongqing and Beijing would have the potential to transmit HIV to female partners. Only 9 (1.8%) men in Chongqing and 2 (0.4%) in Beijing were HIV-positive and also had unprotected intercourse with females. The majority of HIV transmission risk among MSM in China is not from MSM to females.
doi:10.1007/s10461-013-0505-1
PMCID: PMC4441273  PMID: 23666182
MSM, sexual partnerships; China; HIV; risk taking; bridging; female partners
8.  Near Full-Length Genome Characterization of a New CRF01_AE/CRF08_BC Recombinant Transmitted Between a Heterosexual Couple in Guangxi, China 
Abstract
Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE is transmitted mainly by sexual activity in Guangxi, southwestern China. Other subtypes, including CRF07_BC, CRF08_BC, and subtype B, are also prevalent in this region. Cocirculation of multiple subtypes, as well as a high rate of drug use, creates favorable conditions for the emergence of recombinant viruses in Guangxi. In the present study, we identified a new HIV-1 unique recombinant form (CRF01_AE /08BC) transmitted from the infected index patient to his seronegative sexual partner. This is the first near full-length genome characterization of a CRF01_AE /08BC recombinant virus in Guangxi, and provides an important basis for future analysis on potential new recombinant transmission events.
doi:10.1089/aid.2013.0230
PMCID: PMC4010168  PMID: 24164454
9.  Identification of a Novel HIV-1 Circulating Recombinant Form (CRF62_BC) in Western Yunnan of China 
Abstract
We report here a novel HIV-1 circulating recombinant form (CRF62_BC) that was isolated from three epidemiologically unlinked individuals [one from an injecting drug user (IDU); two from heterosexuals] in Dehong prefecture of western Yunnan province. CRF62_BC harbored two subtype B segments in the pol and vpu-env regions in a subtype C backbone. Subregion tree analysis demonstrated that subtype B regions originated from a Thai-B (subtype B′) lineage and the subtype C region was from an India C lineage. CRF62_BC is the fourth CRF composed of subtypes B′ and C known to date after CRF07_BC, CRF08_BC, and CRF57_BC, which were originally found among IDUs in China. The emergence of CRF62_BC may indicate the continual generation of new recombinant strains in various high-risk populations in western Yunnan. This may complicate the development of effective vaccines to limit the HIV-1 epidemic and increase the difficulty of AIDS prevention and control in China.
doi:10.1089/aid.2013.0235
PMCID: PMC3976572  PMID: 24164474
10.  Genome Sequence of a Novel HIV-1 Circulating Recombinant Form (CRF64_BC) Identified from Yunnan, China 
Abstract
We report a novel HIV-1 circulating recombinant form (CRF64_BC) that was isolated from five epidemiologically unlinked HIV-infected persons in Yunnan province. CRF64_BC was composed of subtype B and subtype C, with five short subtype B segments inserted into the subtype C backbone. Phylogenetic analysis demonstrated that the C subregion was correlated with the India C lineage, which was transmitted into China in the early 1990s. The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results. Dehong is considered the epicenter of HIV-1 in China, and recombinant strains such as CRF07_BC and CRF08_BC, which also originated from this region, have spread widely in China. The newly emerged CRF64_BC increases the complexity of the HIV epidemic in China and complicates the development of subtype-specific tools against HIV transmission.
doi:10.1089/aid.2013.0234
PMCID: PMC3976579  PMID: 24205972
11.  Genome Sequence of a Novel HIV-1 Circulating Recombinant Form (CRF57_BC) Identified from Yunnan, China 
Abstract
We identified a novel HIV-1 circulating recombinant form (designated CRF57_BC) from a total of four patients with no obvious epidemiologic linkage in western Yunnan (Dehong prefecture) in China. Two strains (09CN.YNFL37 and 10CN.DHFL17) were identified in this study. An additional two strains (341 and 1439) were found among strains reported in a previous study. CRF57_BC was composed of subtype B and subtype C, with one subtype B segment inserted into the gag region of the subtype C backbone. Subregion tree analysis showed that the B regions originated from a Thai B lineage and the C regions were from an India C lineage. The emergence of CRF57_BC may reflect the continual generation of various forms of intersubtype recombinants in western Yunnan.
doi:10.1089/aid.2013.0228
PMCID: PMC3976592  PMID: 24205935
12.  An ADAM10 promoter polymorphism is a functional variant in severe sepsis patients and confers susceptibility to the development of sepsis 
Critical Care  2015;19(1):73.
Introduction
Although genetic variants of the A disintegrin and metalloproteinase 10 (ADAM10) gene have been shown to be associated with susceptibility to several inflammatory-related diseases, to date little is known about the clinical relationship in the development of sepsis.
Methods
Two genetic variants in the promoter of ADAM10 were selected to analyze the potential association with the risk of sepsis. A total of 440 sepsis patients and 450 matched healthy individuals in two independent Chinese Han population were enrolled. Pyrosequencing and polymerase chain reaction-length polymorphism was used to determine the genotypes of the rs514049 and rs653765. A real-time qPCR method was used to detect the mRNA level of ADAM10. Enzyme-linked immunosorbent assay was used to measure the expression levels of substrates CX3CL1, interleukin (IL)-6R, tumor necrosis factor alpha (TNF-α), and the pro-inflammatory cytokines IL-1β and IL-6. Luciferase assay was used to analyze the activities of the promoter haplotypes of ADAM10.
Results
No statistically significant differences between sepsis cases and controls in the genotype or allele frequencies were observed, suggesting that ADAM10 single nucleotide polymorphisms (SNPs) may not be risk factors for the occurrence of sepsis. A significant difference in the genotype and allele frequencies of the rs653765 SNP between patients with sepsis subtype and severe sepsis (P = 0.0014) or severe sepsis/sepsis shock (P = 0.0037) were observed. Moreover, the rs653765 CC genotype in severe sepsis showed a higher ADAM10 level compared to healthy groups, and the rs653765 CC polymorphism had a strong impact on the production of the ADAM10 substrates CX3CL1, IL-6R and TNF-α. Furthermore, the functional assay showed that ADAM10 C-A haplotype carriers exhibited significantly higher reporter activity compared with the T-A carriers and T-C carriers in human acute monocytic leukemia cell line.
Conclusions
Our data initially indicated the ADAM10 rs653765 polymorphism was associated with the development of severe sepsis; the risk CC genotype could functionally affect the expression level of ADAM10 mRNA and was accompanied by the up-regulation of its substrates. Thus, ADAM10 might be clinically important and play a critical role in the pathogenesis of the development of sepsis, with potentially important therapeutic implications.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-015-0796-x) contains supplementary material, which is available to authorized users.
doi:10.1186/s13054-015-0796-x
PMCID: PMC4373036  PMID: 25888255
13.  HIV-1 transmitted drug resistance-associated mutations and mutation co-variation in HIV-1 treatment-naïve MSM from 2011 to 2013 in Beijing, China 
BMC Infectious Diseases  2014;14:689.
Background
Transmitted drug resistance (TDR) is an important public health issue, because TDR-associated mutation may affect the outcome of antiretroviral treatment potentially or directly. Men who have sex with men (MSM) constitute a major risk group for HIV transmission. However, current reports are scarce on HIV TDR-associated mutations and their co-variation among MSM.
Methods
Blood samples from 262 newly diagnosed HIV-positive, antiretroviral therapy (ART)-naïve MSM, were collected from January 2011 and December 2013 in Beijing. The polymerase viral genes were sequenced to explore TDR-associated mutations and mutation co-variation.
Results
A total of 223 samples were sequenced and analyzed. Among them, HIV-1 CRF01_AE are accounted for 60.5%, followed by CRF07_BC (27.8%), subtype B (9.9%), and others. Fifty-seven samples had at least one TDR-associated mutation, mainly including L10I/V (6.3%), A71L/T/V (6.3%), V179D/E (5.4%), and V106I (2.7%), with different distributions of TDR-associated mutations by different HIV-1 subtypes and by each year. Moreover, eight significant co-variation pairs were found between TDR-associated mutations (V179D/E) and seven overlapping polymorphisms in subtype CRF01_AE.
Conclusions
To date, this work consists the most comprehensive genetic characterization of HIV-1 TDR-associated mutations prevalent among MSM. It provides important information for understanding TDR and viral evolution among Chinese MSM, a population currently at particularly high risk of HIV transmission.
doi:10.1186/s12879-014-0689-7
PMCID: PMC4271504  PMID: 25510523
HIV-1; MSM; Subtypes; Transmitted drug resistance-associated mutations; Co-variation
14.  Near Full-Length Genome Identification of a Novel HIV Type 1 B′/C Recombinant Isolate JL100091 in Jilin, China 
AIDS Research and Human Retroviruses  2013;29(12):1609-1612.
Abstract
We report here a novel HIV-1 B′/C recombinant isolate JL100091, identified from an HIV-positive female subject infected through heterosexual transmission in Jilin in 2006. The near full-length genome analyses of the novel recombinant (JL10091) showed that one subtype B′ region (3,085 bp) was inserted into the subtype C backbone, with two breakpoints observed in gag and pol genes. To our knowledge, this is the first detection of a novel HIV-1 B′/C recombinant in Jilin, which indicates ongoing transmission of networks among the heterosexual population in the region. The novel HIV-1 B′/C recombinant (JL10091) in Jilin originated from India subtype C and China subtype B′ may suggest potential transmission routes of HIV-1 in China. Further monitoring of the molecular epidemiology of the HIV-1 epidemic in Jilin will provide critical information for designing effective control and prevention measures against HIV transmission in the region.
doi:10.1089/aid.2013.0134
PMCID: PMC3848441  PMID: 23800314
15.  The Potential Role of CD16+ Vγ2Vδ2 T Cell-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity in Control of HIV Type 1 Disease 
AIDS Research and Human Retroviruses  2013;29(12):1562-1570.
Abstract
Increasing evidence has suggested that HIV infection severely damages the Vγ2Vδ2 (Vδ2) T cells that play an important role in the first-line host response to infectious disease. However, little is known about Vδ2 T cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in HIV disease. We found that although the CD16+ Vδ2 T cell subset hardly participated in phosphoantigen responses dominated by the CD16− Vδ2 T cell subset, the potency of the ADCC function of Vδ2 T cells was correlated with the frequency of the CD16+ subset. Thus, two distinct and complementary Vδ2 T cell subsets discriminated by CD16 were characterized to explore the respective impacts of HIV-1 infection on them. HIV-1 disease progression was not only associated with the phosphoantigen responsiveness of the CD16− Vδ2 subset, but also with the ability of the CD16+ Vδ2 subset to kill antibody-coated target cells. Furthermore, both of the two Vδ2 functional subsets could be partially restored in HIV-infected patients with antiretroviral therapy. Notably, in the context of an overall HIV-mediated Vδ2 T cell depletion, despite the decline of phosphoantigen-responsive CD16− Vδ2 cells, CD16+ Vδ2 cell-mediated ADCC was not compromised but exhibited a functional switch with dramatic promotion of degranulation in the early phase of HIV infection and chronic infection with slower disease progression. Our study reveals functional characterizations of the two Vδ2 T cell subsets with different activation pathways during HIV-1 infection and provides a rational direction for activating the CD16+ Vδ2 T cells capable of mediating ADCC as a means to control HIV-1 disease.
doi:10.1089/aid.2013.0111
PMCID: PMC3848486  PMID: 23957587
16.  Near Full-Length Genome Sequence of a Novel HIV Type 1 Second-Generation Recombinant Form (CRF01_AE/CRF07_BC) Identified Among Men Who Have Sex with Men in Jilin, China 
AIDS Research and Human Retroviruses  2013;29(12):1604-1608.
Abstract
We report here a novel HIV-1 second-generation recombinant form (CRF01_AE/CRF07_BC) composed of CRF01_AE and CRF07_BC, identified among men who have sex with men (MSM) in Jilin, with four breakpoints observed in the pol, vif, and vpr genes. The CRF01_AE regions of the recombinant were clustered with the CRF01_AE lineage, which is mainly circulating among MSM in northern China, with the support of 100% bootstrap value, indicating that the parental origin of the CRF01_AE regions was from MSM, in which recombination events may be more likely to occur. To the best of our knowledge, this is the first detection of a novel HIV-1 second-generation recombinant form (CRF01AE/CRF07_BC) in Jilin, which indicates active transmission networks of HIV-1 infection among MSM in the region. Therefore, it is necessary to continue monitoring the molecular epidemiology of HIV-1 among MSM in Jilin to obtain a better understanding of the transmission and potential public health impact of HIV-1 among MSM in the region.
doi:10.1089/aid.2013.0116
PMCID: PMC3848684  PMID: 23809010
17.  The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy 
Objective
We built a cohort study of HIV patients taking long-term first-line Antiretroviral Therapy in 2003. In this assay, we focused on the development of primary drug resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), K103N, Y181C and G190A.
Method
The cohort study was built in Henan province, China. We used Single Genome Amplification (SGA) to analyze the frequency of K103N, Y181C and G190A in serial plasma samples of three individual patients. We also performed standard genotype HIV drug resistance assay in 204 patients of this cohort study to analyze the frequency of these mutations.
Result
In the SGA sequences, the K103N decreased and vanished, while the frequency of Y181C and G190A increased in individual patient receiving long-term Antiretroviral Therapy (ART). In the sequences of standard genotype HIV drug resistance assay, the frequency of K103N, Y181C and G190A had the similar pattern with that in SGA sequences. Among these patients, the viral suppression were still sufficient after receiving ART for 72 months, and 78.6% (160/204) patients could have their CD4 count over than 200cells/ul.
Conclusion
In some patients, first-line ART had the possibility to provide sufficient treatment effect for over than 72 months, but in long-term treatment, the dominant NNRTI drug resistance mutation K103N could reduced, while the proportion of variants with mutation Y181C or G190A may increased. This result was not similar with that in vitro study, which state that variant with K103N or Y181C had an equal viral fitness with wild type.
doi:10.1186/1742-6405-11-36
PMCID: PMC4414387  PMID: 25926857
K103N; Y181C; G190A Navirapine (NVP); Antiviral therapy; Cohort study
18.  Molecular Epidemiology of HIV-1 in Jilin Province, Northeastern China: Emergence of a New CRF07_BC Transmission Cluster and Intersubtype Recombinants 
PLoS ONE  2014;9(10):e110738.
Objective
To investigate the HIV-1 molecular epidemiology among newly diagnosed HIV-1 infected persons living in the Jilin province of northeastern China.
Methods
Plasma samples from 189 newly diagnosed HIV-1 infected patients were collected between June 2010 and August 2011 from all nine cities of Jilin province. HIV-1 nucleotide sequences of gag P17–P24 and env C2–C4 gene regions were amplified using a multiplex RT-PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes.
Results
Based on all sequences generated, the subtype/CFR distribution was as follows: CRF01_AE (58.1%), CRF07_BC (13.2%), subtype B’ (13.2%), recombinant viruses (8.1%), subtype B (3.7%), CRF02_AG (2.9%), subtype C (0.7%). In addition to finding CRF01_AE strains from previously reported transmission clusters 1, 4 and 5, a new transmission cluster was described within the CRF07_BC radiation. Among 11 different recombinants identified, 10 contained portions of gene regions from the CRF01_AE lineage. CRF02_AG was found to form a transmission cluster of 4 in local Jilin residents.
Conclusions
Our study presents a molecular epidemiologic investigation describing the complex structure of HIV-1 strains co-circulating in Jilin province. The results highlight the critical importance of continuous monitoring of HIV-infections, along with detailed socio-demographic data, in order to design appropriate prevention measures to limit the spread of new HIV infections.
doi:10.1371/journal.pone.0110738
PMCID: PMC4214716  PMID: 25356726
19.  HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China 
BMJ Open  2014;4(10):e005886.
Objective
To explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.
Design
A series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network.
Setting
China.
Participants
Data were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis.
Results
929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0–17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm3 or from 0 to 199 cells/mm3, and residence of Guangxi and Yunnan provinces.
Conclusions
The proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.
doi:10.1136/bmjopen-2014-005886
PMCID: PMC4202012  PMID: 25319999
20.  Sexual Risk Reduction for HIV-Infected Persons: A Meta-Analytic Review of “Positive Prevention” Randomized Clinical Trials 
PLoS ONE  2014;9(9):e107652.
Background
Prevention intervention trials have been conducted to reduce risk of sexual transmission among people living with HIV/AIDS (PLWHA), but the findings were inconsistent. We performed a systematic review and meta-analysis to evaluate overall efficacy of prevention interventions on unprotected vaginal or anal intercourse (UVAI) among PLWHA from randomized clinical trials (RCTs).
Methods
RCTs of prevention interventions among PLWHA published as of February 2012 were identified by systematically searching thirteen electronic databases. The primary outcome was UVAI. The difference of standardized mean difference (SMD) of UVAI between study arms, defined as effect size (ES), was calculated for each study and then pooled across studies using standard meta-analysis with a random effects model.
Results
Lower likelihood of UVAI was observed in the intervention arms compared with the control arms either with any sexual partners (mean ES: −0.22; 95% confidence interval [CI]: −0.32, −0.11) or with HIV-negative or unknown-status sexual partners (mean ES and 95% CI: −0.13 [−0.22, −0.04]). Short-term efficacy of interventions with ≤10 months of follow up was significant in reducing UVAI (1–5 months: −0.27 [−0.45, −0.10]; 6–10 months: −0.18 [−0.30, −0.07]), while long-term efficacy of interventions was weaker and might have been due to chance (11–15 months: −0.13 [−0.34, 0.08]; >15 months: −0.05 [−0.43, 0.32]).
Conclusions
Our meta-analyses confirmed the short-term impact of prevention interventions on reducing self-reported UVAI among PLWHA irrespective of the type of sexual partner, but did not support a definite conclusion on long-term effect. It is suggested that booster intervention sessions are needed to maintain a sustainable reduction of unprotected sex among PLWHA in future risk reduction programs.
doi:10.1371/journal.pone.0107652
PMCID: PMC4171502  PMID: 25243404
21.  Sex with Women Among Men Who Have Sex with Men in China: Prevalence and Sexual Practices 
AIDS Patient Care and STDs  2013;27(9):524-528.
Abstract
Men who have sex with men and women (MSMW) are a potential bridge population for transmitting HIV to heterosexual women. This study assessed key characteristics of this subgroup of men who have sex with men (MSM) in China. Of 1141 eligible MSM, 45.6% reported bisexual behaviors. Besides marriage as a strong predictor (odds ratio: 23.90, 95% confidence interval: 14.29–39.98), older age (1.12, 1.10–1.15) and lower education (or no college education) (1.98, 1.52–2.59) were also independently associated with having ever had sex with women. MSMW reported higher proportions of alcohol drinking, heterosexual/bisexual orientation, and preference for an insertive role in anal sex than men who had sex with men only; but there was no statistically significant difference between two groups in prevalence of HIV and syphilis infections and in history of sexually transmitted infections. HIV prevention intervention programs should break the bridging role of HIV transmission in MSMW population.
doi:10.1089/apc.2013.0161
PMCID: PMC3760059  PMID: 23931683
22.  Near Full-Length Genomic Characterization of a Novel HIV Type 1 CRF07_ BC/01_AE Recombinant in Men Who Have Sex with Men from Sichuan, China 
AIDS Research and Human Retroviruses  2013;29(8):1173-1176.
Abstract
In recent years, the men who have sex with men (MSM) population has seen the fastest growing prevalence of HIV transmission in China. In addition, coinfection through sex and intravenous drug use is a major problem in HIV prevention and control. Recent studies have also revealed that three major viral strains (CRF07_BC, CRF01_AE, and subtype B) have been cocirculating among MSM in Sichuan, suggesting a high probability of generating new recombinants. This study reports a near full-length genome of a novel HIV-1 recombinant (MSM0720) between CRF07_BC and CRF01_AE. The analysis of MSM0720 shows that the genome is composed of at least 11 interlaced segments, including six CRF07_BC and five CRF01_AE segments, with CRF07_BC as the backbone; this is different from a previously identified CRF01_AE/07_BC recombinant strain in intravenous drug users from Jiangsu.
doi:10.1089/aid.2013.0104
PMCID: PMC3715772  PMID: 23594292
23.  The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population 
PPAR Research  2014;2014:701971.
Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.
doi:10.1155/2014/701971
PMCID: PMC4131125  PMID: 25152754
24.  HIV/AIDS-related stigmatizing and discriminatory attitudes and recent HIV testing among Beijing men who have sex with men 
AIDS and behavior  2012;16(3):499-507.
The study was to assess the correlates for recent HIV testing and HIV/AIDS-related stigmatizing and discriminatory attitudes among men who have sex with men (MSM) in Beijing, China. A cross-sectional study probed demographics, sexual and drug use behaviors, HIV testing, and prevention services. Of 500 participants, 39.3% recently received a test for HIV. Recent testing was independently associated with expressing lower levels of HIV/AIDS-related stigmatizing and discriminatory attitudes, more male sex partners, no female sexual partners and knowing HIV status of their last male partner. Expressing lower levels of HIV/AIDS-related stigmatizing and discriminatory attitudes was independently associated with recent testing, younger age, and knowing HIV status of their last male partner. This study revealed that HIV/AIDS-related stigmatizing and discriminatory attitudes were common and inversely associated with recent HIV testing. Low levels of testing highlighted the urgent needs to reduce HIV/AIDS-related stigma and discrimination and expand HIV testing among Beijing MSM.
doi:10.1007/s10461-012-0161-x
PMCID: PMC4048063  PMID: 22350831
HIV/AIDS; stigma; discrimination; testing; men who have sex with men
25.  Identification of the Critical Sites of NNRTI-Resistance in Reverse Transcriptase of HIV-1 CRF_BC Strains 
PLoS ONE  2014;9(4):e93804.
Background
The polymorphisms involved in drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF_BC, the most prevalent HIV-1 strain in China, have been poorly characterized.
Results
To reveal the drug resistance mutations, we compared the gene sequences of pol region of HIV-1 CRF_BC from 631 treatment-naïve and 363 treatment-experienced patients using the selection pressure-based method. We calculated an individual Ka/Ks value for each specific amino acid mutation. Result showed that eight polymorphic mutations (W88C, K101Q, I132L, R135L, T139K/R, H221Y and L228R) in RT for treatment-experienced patients were identified, while they, except for R135L, were completely absent in those from treatment-naïve patients. The I132L and T139K/R mutants exhibited high-level resistance to DLV and NVP and moderate resistance to TMC-125 and EFV, while the K101Q and H221Y mutants exhibited an increased resistance to all four NNRTIs tested. The W88C, R135L, and L228R may be RTI-induced adaptive mutations. Y181C+K101Q mutant showed a 2.5-, 4.4-, and 4.7-fold higher resistance to TMC-125, NVP and EFV, respectively, than Y181C alone mutant, while Y181C+H221Y or K103N+H221Y mutants had significantly higher resistance to all four NNRTIs than Y181C or K103N mutants. K103N+T139K and G190A+T139K mutant induce higher resistance (2.0∼14.2-fold and 1.5∼7.2-fold, respectively) to all four NNRTIs than K103N or G190A alone mutation.
Conclusions
I132L and T139K/R are rare but critical mutations associated with NNRTI-resistance for some NNRTIs. K101Q, H221Y and T139K can enhance K103N/Y181C/G190A-assocated NNRTI-resistance. Monitoring these mutations will provide useful information for rational design of the NNRTI-based antiretroviral regimen for HIV-1 CRF_BC-infected patients.
doi:10.1371/journal.pone.0093804
PMCID: PMC3990534  PMID: 24743727

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