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1.  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(1):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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  HIV Risk Perception among HIV Negative or Status-Unknown Men Who Have Sex with Men in China 
BioMed Research International  2014;2014:232451.
Objective. To evaluate HIV risk perception and its associated factors among Chinese MSM. Methods. A cross-sectional study was conducted among MSM with an HIV negative or unknown status in Beijing, China, between 2011 and 2012. A questionnaire interview was conducted and a blood sample was collected for HIV and syphilis testing. Results. Of 887 MSM who reported they were HIV negative or did not know their HIV status before recruitment, only 7.3% reported a high risk of HIV infection, 28.0% medium risk, 52.2% low risk, and 12.5% no risk. In multivariate logistic regression models using those who reported a medium self-perceived risk as a reference group, self-reported high risk of HIV perception was associated with minority ethnicity (odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.03–8.19), self-reported history of sexually transmitted diseases (OR: 2.27; 95% CI: 1.25–4.10), and HIV testing times since the last HIV testing (OR: 0.47; 95% CI: 0.26–0.84); low self-perceived risk of HIV infection was related to full-time employment (OR: 1.58; 95% CI: 1.15–2.18) and illicit drug use (OR: 0.28; 95% CI: 0.10–0.75). Conclusions. The HIV/AIDS epidemic is rapidly rising among Beijing MSM, but more than half MSM did not perceive this risk.
doi:10.1155/2014/232451
PMCID: PMC3985141  PMID: 24795880
14.  Alterations in HIV-1 gp120 V3 Region Are Necessary but Not Sufficient for Coreceptor Switching in CRF07_BC in China 
PLoS ONE  2014;9(3):e93426.
The most predominant HIV-1 strains in China's current epidemic is the Circulating Recombinant Form 07_BC (CRF07_BC). CRF07_BC is mainly considered as a CCR5-tropic (R5) virus, since CXCR4-tropic (X4) viruses have thus far not been found in this subtype, and the molecular determinants of coreceptor switching remain unknown. To investigate the mechanisms underlying coreceptor requirement in CRF07_BC viruses, we characterized a panel of pNL4-3-based chimeric viruses with mutated V3 loop regions derived from an HIV-1 CRF07_BC infectious clone pXJDC13. Among 17 chimeric viruses, seven were dual-tropic and induced syncytium formation in MT-2 cells. Two amino acid insertions between positions 13 and 14, as well as arginine substitution at position 11 or 16 (IG insertion and P16R mutation or MG insertion and S11R mutation), conferred the chimeric viruses CXCR4-tropic features, which were same as subtype C X4 viruses. Next, to construct CRF07_BC X4 variants, mutated V3 loops were cloned into the CRF07_BC infectious clone pXJDC13. These V3 loops, which in the pNL4-3 backbone conferred chimeric viruses with CXCR4-using ability, abrogated infectivity completely in the CRF07_BC pXJDC13 genetic background. Similarly, IG insertion or MG insertion and S11R mutation dramatically diminished or completely abolished viral infectivity in other envelopes of subtype C or CRF07_BC. These results suggest that the effects of IG insertion and P16R mutation or MG insertion and S11R mutation on CXCR4 usage are context dependent, and additional mutations elsewhere in the envelope are needed to compensate for these fitness-reducing alterations.
doi:10.1371/journal.pone.0093426
PMCID: PMC3968174  PMID: 24676404
15.  Prevalence and Seroincidence of Hepatitis B and Hepatitis C Infection in High Risk People Who Inject Drugs in China and Thailand 
We determined the prevalence and incidence of HBV and HCV infection in people who inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined the association of HBV and HCV incidence with urine opiate test results and with short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of 201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative participants, the HBsAg incidence rate was 2.7/100 person years in China and 0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence rate among HCV antibody negative PWIDs was 22/100 person years in China and 4.6/100 person years in Thailand. Incident HBsAg was not significantly different in the short-term versus long-term B-N arm in China or Thailand. Participants with positive opiate results in at least 75% of their urines during the time period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to 25.22; P = 0.04) in China, but not incident HCV conversion in China or Thailand.
doi:10.1155/2014/296958
PMCID: PMC3985324  PMID: 24860664
16.  Structural and biochemical insights into the V/I505T mutation found in the EIAV gp45 vaccine strain 
Retrovirology  2014;11:26.
Background
The equine infectious anemia virus (EIAV) is a lentivirus of the Retrovirus family, which causes persistent infection in horses often characterized by recurrent episodes of high fever. It has a similar morphology and life cycle to the human immunodeficiency virus (HIV). Its transmembrane glycoprotein, gp45 (analogous to gp41 in HIV), mediates membrane fusion during the infection. However, the post-fusion conformation of EIAV gp45 has not yet been determined. EIAV is the first member of the lentiviruses for which an effective vaccine has been successfully developed. The attenuated vaccine strain, FDDV, has been produced from a pathogenic strain by a series of passages in donkey dermal cells. We have previously reported that a V/I505T mutation in gp45, in combination with other mutations in gp90, may potentially contribute to the success of the vaccine strain. To this end, we now report on our structural and biochemical studies of the gp45 protein from both wide type and vaccine strain, providing a valuable structural model for the advancement of the EIAV vaccine.
Results
We resolved crystal structures of the ecto-domain of gp45 from both the wild-type EIAV and the vaccine strain FDDV. We found that the V/I505T mutation in gp45 was located in a highly conserved d position within the heptad repeat, which protruded into a 3-fold symmetry axis within the six-helix bundle. Our crystal structure analyses revealed a shift of a hydrophobic to hydrophilic interaction due to this specific mutation, and further biochemical and virological studies confirmed that the mutation reduced the overall stability of the six-helix bundle in post-fusion conformation. Moreover, we found that altering the temperatures drastically affected the viral infectivity.
Conclusions
Our high-resolution crystal structures of gp45 exhibited high conservation between the gp45/gp41 structures of lentiviruses. In addition, a hydrophobic to hydrophilic interaction change in the EIAV vaccine strain was found to modulate the stability and thermal-sensitivity of the overall gp45 structure. Our observations suggest that lowering the stability of the six-helix bundle (post-fusion), which may stabilizes the pre-fusion conformation, might be one of the reasons of acquired dominance for FDDV in viral attenuation.
doi:10.1186/1742-4690-11-26
PMCID: PMC3997929  PMID: 24656154
EIAV; gp45; Crystal structure; Stability; Vaccine strain; Heptad repeat; Pre-fusion conformation; Replication
17.  Modeling the Impact on HIV Incidence of Combination Prevention Strategies among Men Who Have Sex with Men in Beijing, China 
PLoS ONE  2014;9(3):e90985.
Objective
To project the HIV/AIDS epidemics among men who have sex with men (MSM) under different combinations of HIV testing and linkage to care (TLC) interventions including antiretroviral therapy (ART) in Beijing, China.
Design
Mathematical modeling.
Methods
Using a mathematical model to fit prevalence estimates from 2000–2010, we projected trends in HIV prevalence and incidence during 2011–2020 under five scenarios: (S1) current intervention levels by averaging 2000–2010 coverage; (S2) increased ART coverage with current TLC; (S3) increased TLC/ART coverage; (S4) increased condom use; and (S5) increased TLC/ART plus increased condom use.
Results
The basic reproduction number based upon the current level of interventions is significantly higher than 1 ( confidence interval (CI), 1.83–2.35), suggesting that the HIV epidemic will continue to increase to 2020. Compared to the 2010 prevalence of 7.8%, the projected HIV prevalence in 2020 for the five prevention scenarios will be: (S1) Current coverage: 21.4% (95% CI, 9.9–31.7%); (S2) Increased ART: 19.9% (95% CI, 9.9–28.4%); (S3) Increased TLC/ART: 14.5% (95% CI, 7.0–23.8%); (S4) Increased condom use: 13.0% (95% CI, 9.8–28.4%); and (S5) Increased TLC/ART and condom use: 8.7% (95% CI, 5.4–11.5%). HIV epidemic will continue to rise () for S1–S4 even with hyperbolic coverage in the sensitivity analysis, and is expected to decline () for S5.
Conclusion
Our transmission model suggests that Beijing MSM will have a rapidly rising HIV epidemic. Even enhanced levels of TLC/ART will not interrupt epidemic expansion, despite optimistic assumptions for coverage. Promoting condom use is a crucial component of combination interventions.
doi:10.1371/journal.pone.0090985
PMCID: PMC3953201  PMID: 24626165
18.  Alcohol Use among Chinese Men Who Have Sex with Men: An Epidemiological Survey and Meta-Analysis 
BioMed Research International  2014;2014:414381.
The HIV/AIDS epidemic among Chinese men who have sex with men (MSM) has become a significant public health concern. Knowledge of alcohol consumption in this population is limited. In this study, 1,155 Chinese MSM were surveyed to assess alcohol use and its correlates. A meta-analysis was also performed to aggregate pooled prevalence of current alcohol use. MSM who were unmarried (aOR: 1.87; 95% CI: 1.29–2.71) or unemployed/retired (aOR: 2.77; 95% CI: 1.73–4.45) were more likely to drink alcohol more than once per week. MSM who consumed alcohol more than once per week were more likely to use drug (P < 0.01), have sex with women (P < 0.01), have unprotected insertive (P = 0.04) or receptive (P = 0.03) anal sex with men, have more than 10 lifetime male sex partners (P < 0.01), predominantly practice insertive anal sex (P < 0.01), and trade sex for money (P < 0.01). Pooled overall alcohol use prevalence was 32%. Pooled prevalence for MSM who drank alcohol more than once per week and who drank alcohol before sex with male partners was 23%. Our findings provide the basis for further exploring the alcohol-HIV association and developing risk reduction interventions.
doi:10.1155/2014/414381
PMCID: PMC3966324  PMID: 24711993
19.  Efficacy of Peer-Led Interventions to Reduce Unprotected Anal Intercourse among Men Who Have Sex with Men: A Meta-Analysis 
PLoS ONE  2014;9(3):e90788.
Objective
To conduct a systematic review and meta-analysis to evaluate the efficacy of peer-led interventions in reducing unprotected anal intercourse (UAI) among men who have sex with men (MSM).
Methods
Randomized clinical trials (RCTs), quasi-experimental studies, pre- and post-intervention studies without control groups, and serial cross-sectional assessments involving peers delivering interventions among MSM and published as of February 2012 were identified by systematically searching 13 electronic databases and cross-referencing. Effect sizes (ES) were calculated as the changes of standardized mean difference (SMD) in UAI between groups or pre-post intervention.
Results
A total of 22 studies met the eligibility criteria, including five RCTs, six quasi-experimental studies, six pre-and-post intervention studies, and five serial cross-sectional intervention studies. We used 15 individual studies including 17 interventions for overall ES calculation; peer-led interventions reduced UAI with any sexual partners in meta-analysis (mean ES: -0.27; 95% confidence interval [CI]: −0.41, −0.13; P<0.01). Subgroup analyses demonstrated a statistically significant reduction on UAI in quasi-experimental studies (mean ES: −0.30; 95% CI: −0.50, −0.09; P = 0.01) and serial cross-sectional intervention studies (mean ES: −0.33; 95% CI: −0.57, −0.09; P = 0.01), but non-significant reduction in RCTs (mean ES: −0.15; 95% CI: −0.36, 0.07; P = 0.18) or pre- and post-intervention studies (mean ES: −0.29; 95% CI: −0.69, 0.11; P = 0.15). Heterogeneity was large across these 15 studies (I2 = 77.5%; P<0.01), largely due to pre-and-post intervention studies and serial cross-sectional intervention studies.
Conclusions
Peer-led HIV prevention interventions reduced the overall UAI among MSM, but the efficacy varied by study design. More RCTs are needed to evaluate the effect of peer-led interventions while minimizing potential bias.
doi:10.1371/journal.pone.0090788
PMCID: PMC3948720  PMID: 24614809
20.  The Functional Polymorphisms of miR-146a Are Associated with Susceptibility to Severe Sepsis in the Chinese Population 
Mediators of Inflammation  2014;2014:916202.
MicroRNA-146a (miR-146a) acts as a pivotal regulatory molecule in immune response and various diseases, such as carcinoma and autoimmune diseases. Growing evidences have demonstrated the association of miR-146a gene single-nucleotide polymorphisms (SNPs) with risk of several diseases, but no genetic relevance studies of miR-146a gene polymorphisms to sepsis have been reported by now. Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095329 A/G in a Chinese Han population (226 sepsis cases; 206 healthy controls). Our results indicated a higher prevalence of the miR-146a gene SNP rs2910164 C allele and CC genotype in patients with severe sepsis (rs2910164G versus rs2910164C: P = 0.0029, odds ratio (OR) = 1.664; GG+GC versus CC: P = 0.0045, OR = 1.947). Neither the genotype nor the allele in rs57095329 showed significant differences between the septic cases and the controls (P = 0.5901 and 0.3580, resp.), and no significant difference was observed in the subgroups. In addition, we confirmed that the two SNPs rs2910164 and rs57095329 could functionally affect the miR-146a expression levels and the reduction of miR146a was accompanied with the upregulation of the expression levels of TRAF-6 and IRAK-1 in severe sepsis patients. This present study might provide valuable clinical evidence that miR-146a gene polymorphism rs2910164 is associated with the risk of severe sepsis.
doi:10.1155/2014/916202
PMCID: PMC3950573  PMID: 24701036
21.  Virological Outcomes and Drug Resistance in Chinese Patients after 12 Months of 3TC-Based First-Line Antiretroviral Treatment, 2011–2012 
PLoS ONE  2014;9(2):e88305.
Objective
To determine the prevalence of virological failure and HIV drug resistance among Chinese patients one year after initiating lamivudine-based first-line antiretroviral treatment.
Methods
A prospective cohort study with follow-up at 12 months was conducted in four urban sentinel sites in China. Antiretroviral naive patients ≥18 years old were recruited. Blood samples were collected for testing CD4 cell count, viral load, and (for samples with HIV-1 RNA ≥1000 copies/ml) genotyping of drug resistance.
Results
A total of 513 patients were enrolled in this cohort, of whom 448 (87.3%) were retained at 12 months. The median final CD4 cell count was 313 cells/mm3, which increased from 192 cells/mm3 at baseline (P<0.0001). Of the 448 remaining subjects, 394 (87.9%) had successful virological suppression (HIV RNA <1000 copies/ml). Among 54 samples with viral load ≥1000 copies/ml, 40 were successfully genotyped, and 11 were found with detectable HIV drug resistance mutations. Of these, the proportions of drug resistance to NNRTIs, NRTIs and PIs were 100%, 81.8% and 0%, respectively. Injecting drug use (AOR = 0.40, 95% CI: 0.19,0.84; P = 0.0154), CD4 count at baseline ≥350 cells/mm3 (AOR = 0.32, 95% CI: 0.14,0.72; P = 0.0056), and missed doses in the past month (AOR = 0.30, 95% CI: 0.15,0.60; P = 0.0006) were significantly negatively associated with HIV RNA <1000 copies/ml.
Conclusions
Our study demonstrates effective virological and immunological outcomes at 12 months among these who initiated first-line ART treatment. However, patients infected through drug injection, who missed doses, or with higher CD4 count at baseline are at increased risk for poor virological response.
doi:10.1371/journal.pone.0088305
PMCID: PMC3917868  PMID: 24516631
22.  Changing the Landscape of the HIV Epidemic among MSM in China: Results from Three Consecutive Respondent-Driven Sampling Surveys from 2009 to 2011 
BioMed Research International  2014;2014:563517.
This study assessed the changes of HIV incidence and its predictors among Beijing's men who have sex with men (MSM). Three consecutive cross-sectional surveys were carried out using a consistent respondent-driven sampling (RDS) approach in 2009, 2010, and 2011, respectively. Structured-questionnaire based interviews were completed with computer-assisted self-administration. Incident infection was examined with BED capture enzyme immunoassay (BED-CEIA). The overall rate of HIV prevalence was 8.0% in the three years (95% confidence interval [CI]: 4.9%–11.2%). The overall rate of BED-CEIA incidence was 7.8/100 person years (PY) (95% CI: 5.5–10.1) with 6.8/100PY (95% CI: 3.4–10.2) in 2009, 11.2/100PY (95% CI: 6.2–16.3) in 2010, and 5.8/100PY (95% CI: 2.4–9.3) in 2011, respectively. Multivariable logistic regression analysis revealed that, compared with HIV-negative MSM, recently infected MSM were more likely to be bisexual (adjusted odds ratio [AOR] = 2.1, 95% CI: 1.1–4.1), live in Beijing ≤3 years (AOR = 2.1, 95% CI: 1.2–4.0), and have a negative attitude towards safe sex (AOR = 1.1 per scale point, 95% CI: 1.0–1.1). This study demonstrated a disturbing rise of HIV infections among Beijing's MSM. These findings underscored the urgency of scaling up effective and better-targeted intervention services to stop the rapid spread of the virus.
doi:10.1155/2014/563517
PMCID: PMC3918367  PMID: 24575408
23.  HIV, Syphilis, and Behavioral Risk Factors among Female Sex Workers before and after Implementation of Harm Reduction Programs in a High Drug-Using Area of China 
PLoS ONE  2014;9(1):e84950.
Objective
To evaluate the impact of harm reduction programs on HIV and syphilis infection and related risk behaviors among female sex workers (FSWs) in a drug trafficking city in Southwest China.
Design
Before and after harm reduction program study.
Methods
Two cross-sectional surveys were conducted among FSWs before and after harm reduction programs were launched in Xichang city, Sichuan province. The first and second cross-sectional surveys were conducted in 2004 and 2010, respectively. Temporal changes in odds of HIV, syphilis, and behavioral risk factors were assessed by multivariable logistic regression while controlling for socio-demographics.
Results
The 2004 and 2010 cross-sectional surveys recruited 343 and 404 FSWs, respectively. From 2004 to 2010, the odds of syphilis infection decreased by 35% and was of borderline statistical significance (AOR: 0.65, 95% CI: 0.41–1.03), while odds of HIV infection rose, but not significantly (AOR: 4.12, 95% CI: 0.76–22.45). Although odds of unprotected sex with primary sex partners did not significantly change over time (AOR: 0.96; 95% CI: 0.61–1.50), odds of unprotected sex with clients declined significantly and remarkably (AOR: 0.14, 95% CI: 0.09–0.21). Notably, the odds of reporting ≥10 new sex partners in the previous month increased by 37% (AOR: 1.37; 95% CI: 0.98–1.90).
Conclusions
Harm reduction strategies may be an effective means of reducing unprotected sex with clients among FSWs. Future research is needed to better target both FSWs and IDUs and interrupt bridging networks for HIV transmission in high drug-using areas of China.
doi:10.1371/journal.pone.0084950
PMCID: PMC3885653  PMID: 24416319
24.  Correction: Willingness to Use the Oral Fluid HIV Rapid Test among Men Who Have Sex with Men in Beijing, China 
PLoS ONE  2014;9(1):10.1371/annotation/47ef6213-e854-4dca-b321-704c261c6167.
doi:10.1371/annotation/47ef6213-e854-4dca-b321-704c261c6167
PMCID: PMC3883729
25.  Short Communication: Emerging Transmitted HIV Type 1 Drug Resistance Mutations Among Patients Prior to Start of First-Line Antiretroviral Therapy in Middle and Low Prevalence Sites in China 
AIDS Research and Human Retroviruses  2012;28(12):1637-1639.
Abstract
It is known that transmitted drug resistance (TDR) will most likely emerge in regions where antiretroviral therapy (ART) has been widely available for years. However, after a decade of rapid scale-up of ART in China, there are few data regarding TDR among HIV-infected patients prior to initiating first-line ART in China. A prospective, observational cohort study was performed at sentinel sites in five provinces or municipalities. Study participants were recruited at the county- or city-level centers for disease control (CDCs), during routine monitoring visits following referral from diagnosing parties (e.g., hospitals). Each province or municipality recruited 140 patients through sequential sampling throughout the 2011 calendar year. A total of 627 eligible subjects were included in the analysis. the median CD4+ cell count was 206 cells/ml at the baseline survey. The majority of patients (93.5%) had plasma HIV viral load ≥1,000 copies/ml. Of the 627 patients, 17 (2.7%) had drug resistance mutations for any type of HIV drugs. The prevalence of drug resistance mutations to nonnucleoside reverse transcriptase inhibitor (NNRTI) drugs (8/627, 1.3%) was higher than to nucleoside reverse transcriptase inhibitor (NRTI) drugs (5/627, 0.8%) and protease inhibitor (PI) drugs (4/627, 0.6%). A logistic regression model showed that the only predictive factor was the route of infection through homosexual intercourse, i.e., men who have sex with men (MSM) status. As HIV prevalence is rising rapidly among Chinese MSM, it is essential to continue surveying this risk group and related high-risk populations with low awareness of HIV, and to develop new public health interventions that help to reduce the spread of drug-resistant HIV.
doi:10.1089/aid.2012.0164
PMCID: PMC3505058  PMID: 22822770

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