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author:("Ruan, yuhuan")
1.  Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China 
PLoS ONE  2016;11(12):e0166661.
Background
China’s National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.
Method
A cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous blood was sampled for CD4 cell counts, measurement of the HIV viral load (VL), and HIV drug resistance (HIVDR) genotyping. Possible risk factors for HIVDR were analyzed by the logistic regression model.
Results
The study included 765 patients. Among them, 65 patients (8.5%) had virological failure (VLF) defined as ≥1,000 copies/ml. Among the individuals with VLF, 64 were successful genotyped, and of these, 33 had one or more HIVDR mutations. The prevalence of HIVDR mutations among patients receiving first-line ART was 4.3% (33/765). All of the patients with HIVDR mutations were resistant to non-nucleoside transcriptase inhibitors, 81.8% were resistant to nucleoside reverse transcriptase inhibitors, and only 3% had mutations that caused resistance to protease inhibitors. Having lower ratios of drug intake in the past month and dwelling in two southwestern provinces were factors independently associated with the emergence of HIVDR.
Conclusion
Most patients receiving first-line ART treatment achieved sound virological and immunological outcomes. However, poor adherence is still a key problem, which has led to the high rate of HIVDR. It was notable that the proportion of drug resistance widely varied among the provinces. More studies are needed to focus on adherence.
doi:10.1371/journal.pone.0166661
PMCID: PMC5172524  PMID: 27997554
2.  Qualitative Assessment of Barriers and Facilitators of Access to HIV Testing Among Men Who Have Sex with Men in China 
AIDS Patient Care and STDs  2015;29(9):481-489.
Abstract
Diagnosis of HIV is the entry point into the continuum of HIV care; a well-recognized necessary condition for the ultimate prevention of onward transmission. In China, HIV testing rates among men who have sex with men (MSM) are low compared to other high risk subgroups, yet experiences with HIV testing among MSM in China are not well understood. To address this gap and prepare for intervention development to promote HIV testing and rapid linkage to treatment, six focus groups (FGs) were conducted with MSM in Beijing (40 HIV-positive MSM participated in one of four FGs and 20 HIV-negative or status unknown MSM participated in one of two FGs). Major themes reported as challenges to HIV testing included stigma and discrimination related to HIV and homosexuality, limited HIV knowledge, inconvenient clinic times, not knowing where to get a free test, fear of positive diagnosis or nosocomial infection, perceived low service quality, and concerns/doubts about HIV services. Key facilitators included compensation, peer support, professionalism, comfortable testing locations, rapid testing, referral and support after diagnosis, heightened sense of risk through engagement in high-risk behaviors, sense of responsibility to protect self, family and partner support, and publicity via social media. Themes and recommendations were generally consistent across HIV-positive and negative/status unknown groups, although examples of enacted stigma were more prevalent in the HIV-positive groups. Findings from our study provide policy suggestions for how to bolster current HIV prevention intervention efforts to enhance ‘test-and-treat’ strategies for Chinese MSM.
doi:10.1089/apc.2015.0083
PMCID: PMC4553375  PMID: 26186029
3.  Genomic Characterization of Two Novel HIV-1 Unique (CRF01_AE/B) Recombinant Forms Among Men Who Have Sex with Men in Beijing, China 
Abstract
We report here two novel HIV-1 recombinant forms (CRF01_AE/B) isolated from two HIV-positive male subjects infected through homosexual contact in Beijing, China. Recombination contributes substantially to the genetic diversity of HIV-1, and is likely to occur in populations in which multiple subtypes circulate. Molecular epidemiological studies showed that subtype B, CRF01_AE, and CRF07_BC are currently cocirculating in parallel among men who have sex with men (MSM) in China, providing the opportunity for the emergence of new recombinants. Phylogenetic analysis of near full-length genome (NFLG) sequences showed that the unique recombinant forms (URFs) were composed of gene regions from CRF01_AE and subtype B. The CRF01_AE region of the recombinants clustered together with a previously described cluster 4 lineage of CRF01_AE. The B regions of both the recombinants clustered within the B strains. The two recombinants were quite similar with six breakpoints in common. These data highlight the importance of continuous surveillance of the dynamic change of HIV-1 subtypes and new recombinants among the MSM population.
doi:10.1089/aid.2015.0076
PMCID: PMC4553378  PMID: 26058342
4.  Declining Inconsistent Condom Use but Increasing HIV and Syphilis Prevalence Among Older Male Clients of Female Sex Workers 
Medicine  2016;95(22):e3726.
Abstract
Clients of female sex workers (CFSWs) are a bridge population for the spread of HIV and syphilis to low or average risk heterosexuals. Most studies have examined the point prevalence of these infections in CFSWs. Limited evidence suggests that older age CFSWs are at a higher risk of acquiring sexually transmitted diseases compared with younger clients. Thus, we sought to describe long-term trends in HIV, syphilis, and hepatitis C (HCV) to better understand how these infections differ by sex worker classification and client age. We also examined trends in HIV, syphilis, and HCV among categories of female sex workers (FSWs).
We conducted serial cross-sectional studies from 2010 to 2015 in Guangxi autonomous region, China. We collected demographic and behavior variables. FSWs and their clients were tested for HIV, syphilis, and HCV antibodies. Positive HIV and syphilis serologies were confirmed by Western blot and rapid plasma regain, respectively. Clients were categorized as middle age (40–49 years) and older clients (≥50 years). FSWs were categorized as high-tier, middle-tier, or low-tier based on the payment amount charged for sex and their work venue. Chi-square test for trends was used for testing changes in prevalence over time.
By 2015, low-tier FSWs (LTFSWs) accounted for almost half of all FSWs; and they had the highest HIV prevalence at 1.4%. HIV prevalence declined significantly for FSWs (high-tier FSW, P = 0.003; middle-tier FSWs; P = 0.021; LTFSWs, P < 0.001). Syphilis infections significantly declined for FSWs (P < 0.001) but only to 7.3% for LTFSWs. HCV and intravenous drug use were uncommon in FSWs. HIV prevalence increased for older age clients (1.3%–2.0%, P = 0.159) while syphilis prevalence remained stable. HCV infections were halved among older clients in 3 years (1.7%–0.8%, P < 0.001). Condom use during the last sexual encounter increased for FSWs and CFSWs. Few clients reported sex with men or intravenous drug use. Clients preferred LTFSWs, especially older clients (81.9%).
Our results suggest that HIV and syphilis infections are increasing in older clients who prefer LTFSWs. HIV and syphilis are likely increasing in Guangxi Province through heterosexual transmission.
doi:10.1097/MD.0000000000003726
PMCID: PMC4900708  PMID: 27258500
5.  Lamivudine Concentration in Hair and Prediction of Virologic Failure and Drug Resistance among HIV Patients Receiving Free ART in China 
PLoS ONE  2016;11(4):e0154421.
Background
The assessment of adherence to antiretroviral therapy (ART) is important in order to predict treatment outcomes. Lamivudine (3TC) is one of the most widely used NRTIs in China, but its concentrations in hair and association with virologic failure and drug resistance have not been studied.
Methods
We conducted a cross-sectional survey to investigate 3TC concentrations in hair as a predictor of virologic failure and drug resistance among HIV patients receiving free ART. We also compared the capacity of hair 3TC concentrations with self-reported adherence in predicting virologic responses. Hair 3TC concentrations were detected through the LC-MS/MS system.
Results
In patients without HIV drug resistance (HIVDR), with a threshold hair 3TC concentration of 260 ng/g, the sensitivity and specificity in predicting virologic suppression were 76.9% and 89.9%, respectively. Some factors, including CD4+ cell counts, initial treatment regimens with 3TC, and current regimens with second-line drugs, influenced the association between hair 3TC concentrations and virologic suppression. In patients who experienced virologic failure with HIVDR, with a threshold of 180 ng/g, the sensitivity and specificity were 70.0% and 74.4%, respectively. Hair 3TC concentrations had higher sensitivity and specificity in predicting virologic failure and drug resistance than self-reported adherence.
Conclusions
The hair 3TC concentration was a stronger indicator than self-reported adherence in predicting virologic failure and drug resistance in HIV patients receiving free ART.
doi:10.1371/journal.pone.0154421
PMCID: PMC4847920  PMID: 27119346
6.  Expanding substance use treatment options for HIV prevention with Buprenorphine-Naloxone: HIV Prevention Trials Network 058 (HPTN 058) 
Background
Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited.
Methods
HPTN 058 was a randomized controlled trial designed to compare the impact of two medication assisted treatment (MAT) strategies on HIV incidence or death among opioid dependent people who inject drugs (PWID). HIV-negative opiate dependent PWID were recruited from four communities in Thailand and China with historically high prevalence of HIV among PWID. 1251 participants were randomly assigned to either; 1) a one year intervention consisting of two opportunities for a 15 day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling (Short Term Medication Assisted Treatment: ST-MAT) or, 2) thrice weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions (Long Term Medication Assisted Treatment: LT-MAT) followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact.
Results
While the study was stopped early due to lower than expected occurrence of the primary endpoints, sufficient data were available to assess the impact of the interventions on drug use and injection related risk behavior. At weeks 26, 22% of ST-MAT participants had negative urinalyses for opioids compared to 57% in the LT-MAT (p<0.001). Differences disappeared in the year following treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection related risk behaviors were significantly reduced in both groups following randomization.
Conclusions
Participants receiving BUP/NX three times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection related risk behavior. These data support the use of thrice weekly BUP/NX as a way to reduce exposure to HIV risk. Continued access to BUP/NX may be required to sustain reductions in opioid use.
doi:10.1097/QAI.0000000000000510
PMCID: PMC4382671  PMID: 25564105
7.  Genomic Characterization of Two Novel HIV-1 Second-Generation Recombinant Forms Among Men Who Have Sex with Men in Beijing, China 
Abstract
We report two different unique HIV-1 recombinant viruses from two HIV-positive men who have sex with men (MSM) in Beijing, China. Phylogenetic analysis of near full-length genomes (NFLG) showed that the unique recombinant forms (URFs) were comprised of gene regions from two circulating recombinant forms, CRF01_AE and CRF07_BC, both common in China. The parental CRF01_AE region of the recombinants clustered together with a previously described cluster 4 lineage of CRF01_AE. The CRF07_BC regions of both the recombinants clustered within the CRF07_BC radiation, but were distinct from other CRF07_BC reference sequences. The two recombinant forms had two breakpoints in common. The emergence of the two URFs indicates the ongoing generation of recombinant viruses involving CRF01_AE and CRF07_BC, and may provide insight into our understanding of the dynamics and complexity of the HIV-1 epidemic in China.
doi:10.1089/aid.2014.0307
PMCID: PMC4348344  PMID: 25495675
8.  Incidence of Co-Infections of HIV, Herpes Simplex Virus Type 2 and Syphilis in a Large Cohort of Men Who Have Sex with Men in Beijing, China 
PLoS ONE  2016;11(1):e0147422.
Background
The HIV-epidemic among MSM in China has worsened. In this key population, prevalence of HSV-2 and syphilis infection and co-infection with HIV is high.
Methods
A longitudinal study was conducted (n = 962) in Beijing, China, with three overlapping cohorts (n = 857, 757 and 760) consisting of MSM that were free from pairs of infections of concern (i.e. HIV-HSV-2, HIV-syphilis, HSV-2-syphilis) at baseline to estimate incidence of HIV, HSV-2, syphilis, and those of co-infection.
Results
The incidence of HIV, HSV-2 and syphilis in the overall cohort was 3.90 (95% CI = 2.37, 5.43), 7.87 (95% CI = 5.74, 10.00) and 6.06 (95% CI = 4.18, 7.94) cases per 100 person-years (PYs), respectively. The incidence of HIV-HSV-2, HIV-Syphilis and HSV-2-Syphilis co-infections was 0.30 (95% CI = 0.29, 0.88), 1.02 (95% CI = 0.13, 2.17) and 1.41 (95% CI: 0.04, 2.78) cases per 100 PYs, respectively, in the three sub-cohorts constructed for this study.
Conclusions
The incidence of HIV, HSV-2 and syphilis was very high and those of their co-infections were relatively high. Such co-infections have negative impacts on the HIV/STI epidemics. Prevention practices need to take such co-infections into account.
doi:10.1371/journal.pone.0147422
PMCID: PMC4731205  PMID: 26820145
9.  Geographic origin and evolutionary history of China’s two predominant HIV-1 circulating recombinant forms, CRF07_BC and CRF08_BC 
Scientific Reports  2016;6:19279.
To determine the origin and evolutionary history of two predominant and closely-related circulating recombinant forms (CRF07_BC and CRF08_BC), recombinant structures and phylogenies of 7 unique recombinant forms comprised of subtypes of B’ (Thai B linage) and C (designated URFs_BC) from archival specimens of injection drug users (IDUs) collected in 1996 to 1998 from western Yunnan and 4 circulating recombinant forms with B’/C recombinants recently identified (designated nCRFs_BC) in China were compared with those of CRF07_BC and CRF08_BC. The results showed that 5 of 7 URFs_BC and all the nCRFs_BC shared recombination breakpoints with CRF07_BC and/or CRF08_BC. Yunnan URFs_BC consistently occupied the basal branch positions compared with CRF07_BC, CRF08_BC, and nCRFs_BC in phylogenetic trees. The estimated most recent common ancestors (tMRCA) for Yunnan URFs_BC were from ~1987, approximately half a decade earlier than those for CRF07_BC (~1994) and CRF08_BC (~1992). Discrete phylogeographic and spatial diffusion analysis revealed that both CRF07_BC and CRF08 BC came from western Yunnan in the early 1990s. Our results provide compelling evidence for western Yunnan as the geographic origin of CRF07_BC and CRF08_BC, which emerged from a swarm of URFs_BC by a series of recombination events in western Yunnan in the early 1990s.
doi:10.1038/srep19279
PMCID: PMC4725877  PMID: 26763952
10.  Predictors of antiretroviral therapy initiation: a cross-sectional study among Chinese HIV-infected men who have sex with men 
BMC Infectious Diseases  2015;15:570.
Background
Early antiretroviral therapy (ART) initiation is crucial to achieve HIV viral suppression and reduce transmission. HIV-infected Chinese men who have sex with men (MSM) were less likely to initiate ART than other HIV-infected individuals. We assessed predictors of ART initiation among Chinese MSM.
Methods
In 2010–2011, a cross-sectional study was conducted among MSM in Beijing, China. We examined ART initiation within the subgroup who were diagnosed with HIV infection prior to participation in the survey. Logistic regression models were fitted to evaluate socio-demographic and behavioral factors associated with ART initiation. The eligibility criterion in the 2010/2011 national HIV treatment guidelines was CD4 cell count <350 cells/μL or World Health Organization (WHO) clinical stage III/IV.
Results
Of 238 eligible HIV-infected participants, the median duration of HIV infection was 15 months (range: 31 days-12 years); 62 (26.1 %) had initiated ART. Among 103 men with CD4 counts <350 cells/μL, 38 (36.9 %) initiated ART. Being married to a woman (adjusted odd ratios [aOR]: 2.50; 95 % confidence interval [CI]: 1.07-5.87), longer duration of HIV infection (aOR: 10.71; 95 % CI: 3.66-31.32), and syphilis co-infection (aOR: 2.58; 95 % CI: 1.04-6.37) were associated with a higher likelihood of ART initiation. Of 135 men with CD4 count ≥350 cells/μL, 24 (18 %) initiated ART. Being married to a woman (aOR: 4.21; 95 % CI: 1.60-11.06), longer duration of HIV infection (aOR: 22.4; 95 % CI: 2.79-180), older age (aOR: 1.26; 95 % CI: 1.1-1.44), Beijing Hukou (aOR: 4.93; 95 % CI: 1.25-19.33), presence of AIDS-like clinical symptoms (aOR: 3.97; 95 % CI: 1.32-14.0), and history of sexually transmitted infections (aOR: 4.93; 95 % CI: 1.25-19.43) were associated with ART initiation. Compared with men who did not initiated ART, those with ART were more likely to receive counseling on benefits of ART (96.8 % vs. 66.4 %, P = 0 < 0.01), HIV stigma coping strategy (75.8 % vs. 65.9 %, P = 0.04), mental health (66.1 % vs. 52.9 %, P = 0.02), and substance use (46.7 % vs. 36.6 %, P = 0.04).
Conclusions
We documented low rates of ART initiation among Chinese MSM. Policy changes for expanding ART eligibility and interventions to improve the continuum of HIV care are in progress in China. Impact evaluations can help assess continuing barriers to ART initiation among MSM.
doi:10.1186/s12879-015-1309-x
PMCID: PMC4696158  PMID: 26714889
HIV, antiretroviral therapy; Continuum of care; Men who have sex with men; China
11.  Trends of HIV subtypes and phylogenetic dynamics among young men who have sex with men in China, 2009–2014 
Scientific Reports  2015;5:16708.
To investigate the origins of HIV transmission and phylogenetic dynamics among men who have sex with men (MSM), a total of 1205 newly diagnosed HIV-infected 16–25 year-olds were recruited in 13 provinces across China between 2009 and 2014. Based on phylogenetic analyses of partial pol sequences, HIV-1 subtypes including CRF01_AE (45.3%), CRF07_BC (37.8%), subtype B (6.1%), and B’ (3.7%), as well as some other recombinants (7.1%) were identified. In addition to two distinct CRF01_AE clusters [cluster 4 (33.7%, 406/1205) and cluster 5 (7.1%, 85/1205)], we identified a new CRF07_BC cluster (cluster 1) (36.0%, 434/1205), which entered Chinese MSMs in 2004, and had been rapidly spreading since about 2004, which indicating the third wave of the HIV epidemic among the population. Moreover, two new clusters of CRF_01B recombinants were found in this study. The complexities of HIV subtypes and recombinants strongly supports the necessity for a comprehensive study about risk behaviors and their relationship with increasing HIV epidemic subtypes among the MSM group. Implementation and evaluation of comprehensive harm reduction strategies in Chinese MSM are urgently needed.
doi:10.1038/srep16708
PMCID: PMC4649359  PMID: 26577039
12.  Low Virologic Failure and Drug Resistance among HIV-Infected Patients Receiving Hospital-Based ART While Care and Outreach through Community in Guangxi, China 
Objectives
To investigate human immunodeficiency virus (HIV) virologic suppression and drug resistance among HIV-infected patients receiving first-line antiretroviral treatment (ART) in hospitals while community care and outreach through local health workers in Guangxi, China.
Design
This was a series of cross-sectional surveys from 2004 to 2012 in Guangxi, supported by the Chinese National HIVDR Surveillance and Monitoring Network Working Group.
Settings
Guangxi, China.
Methods
Demographic, ART, and laboratory data (CD4+ cell count, viral load, and drug resistance) were analyzed. Factors associated with virologic suppression were identified by logistic regression analysis.
Results
A total of 780 patients were included in this study. The median treatment duration was 20.6 months (IQR 6.6–35.9). Of 780 study participants, 95.4% of patients (744/780) had HIV virologic suppression. Among these, of the 143 patients who were infected through drug injection, only 10 (7.0%) experienced virologic failure, and the overall prevalence of HIV drug resistance was 2.8% (22/789). Factors associated with virologic suppression in the final multivariate models included self-reported missing doses in the past month (compared to not missing doses in the past month, AOR = 0.2, 95% CI: 0.1–0.6) and initial ART regimen without 3TC (compared to initial ART regimen with 3TC, AOR = 0.2, 95% CI: 0.1–0.4). Moreover, the trend chi-square test showed that the proportion of virologic suppression increased over time from 2004 to 2012 (P = 0.002).
Conclusion
This study first demonstrated that HIV patients infected through various transmission routes can achieve an excellent treatment outcome in hospitals at or above the county level for free first-line ART in Guangxi. It is an important of ART education and adherence to intervention for achieving better treatment outcomes.
doi:10.3389/fpubh.2015.00244
PMCID: PMC4621383  PMID: 26579506
HIV; antiretroviral treatment; virologic suppression; drug resistance; China
13.  Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China 
Scientific Reports  2015;5:14823.
Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA ≥ 1000 copies/ml before switch, the proportion of viral load (VL) ≥ 1000 copies/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA < 1000 copies/ml before switch, the proportion of VL ≥ 1000 copies/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3%, and 1.1% before regimen switch to 26.8%, 18.3%, and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA ≥ 1000 copies/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China.
doi:10.1038/srep14823
PMCID: PMC4597210  PMID: 26445885
14.  Acceptability of Male Circumcision among College Students in Medical Universities in Western China: A Cross-Sectional Study 
PLoS ONE  2015;10(9):e0135706.
Background
Male circumcision (MC) has been shown to reduce the risk of female to male transmission of HIV. The goal of this survey was to explore MC’s acceptability and the factors associated with MC among college students in medical universities in western China.
Methods
A cross-sectional study was carried out in three provinces in western China (Guangxi, Chongqing and Xinjiang) to assess the acceptability of MC as well as to discover factors associated with the acceptability among college students in medical universities. A total of 1,790 uncircumcised male students from three medical universities were enrolled in this study. In addition, 150 students who had undergone MC were also enrolled in the survey, and they participated in in-depth interviews.
Results
Of all the uncircumcised participants (n = 1,790), 55.2% (n = 988) were willing to accept MC. Among those who accepted MC, 67.3% thought that MC could improve their sexual partners’ hygiene, 46.3% believed that HIV and sexually transmitted diseases (STDs) could be partially prevented by MC. The multivariable logistic regression indicates that MC’s acceptability was associated with three factors: the redundant foreskin (OR = 10.171, 95% CI = 7.629–13.559), knowing the hazard of having a redundant foreskin (OR = 1.597, 95% CI = 1.097–2.323), and enhancing sexual pleasure (OR = 1.628, 95% CI = 1.312–2.021). The in-depth interviews for subjects who had undergone MC showed that the major reason for having MC was the redundant foreskin (87.3%), followed by the benefits and the fewer complications of having MC done. In addition, most of these participants (65.3%) said that the MC could enhance sexual satisfaction.
Conclusions
MC’s acceptance among college students in medical universities is higher than it is among other populations in western China. An implementation of an MC programme among this population is feasible in the future.
doi:10.1371/journal.pone.0135706
PMCID: PMC4577094  PMID: 26390212
15.  Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand* 
Drug and alcohol dependence  2014;0:139-145.
Background
Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX.
Methods
We compared rates of alanine aminotransferase (ALT) elevation ≥ grade 3 (ALT ≥ 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants.
Results
Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation ≥ grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations ≥ grade 2 occurred in 2% of subjects, with no significant difference between arms.
Conclusions
Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors.
doi:10.1016/j.drugalcdep.2014.06.013
PMCID: PMC4127183  PMID: 24999060
buprenorphine/naloxone; injection drug use; opioid dependence; HIV prevention; safety; hepatotoxicity; alanine aminotransferase; hepatitis C virus
16.  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
17.  HIV-1 Treatment-as-Prevention 
Medicine  2015;94(24):e902.
Abstract
The Chinese national observational cohort study suggests that the treatment-as-prevention (TasP) approach can be an effective public health HIV-1 prevention strategy. However, results from that study may have been biased because the follow-up time of index patients prior to their initiation of antiretroviral therapy (ART) was excluded. In this study, we correct for such bias by using an extended time-dependent Cox regression model to conduct a cohort study analysis of serodiscordant couples in Guangxi of China, inclusive of all follow-up time.
During the follow-up of this observational cohort study of HIV-1 sero-discordant couples, the positive index partners may have never be treated with ART, or enter untreated but subsequently began treatment, or may have been treated immediately upon entry into the public health system. The treatment effectiveness of ART in HIV-1 acquisition among HIV-negative partners is assessed by the extended Cox regression model with treatment status as a time-varying covariate.
A total of 6548 sero-discordant couples were included in the cohort study analysis. Among them, 348 negative partners sero-converted. HIV seroincidence was significantly higher among the nontreated (4.3 per 100 person-years, 3.7–4.9) compared with those receiving ART (1.8 per 100 person-years, 1.5–2.0). An overall 35% reduction in risk of HIV transmission was associated with receiving ART (adjusted hazard ratio [AHR] 0.65, 95% confidence interval [CI] 0.51–0.83), and the yearly risk reduction was also significant in the first 3 consecutive years of follow-up. Moreover, ART was found to be significantly inversely associated with multiple baseline characteristics of index partners.
TasP may be feasible on a national or regional scale. In addition to other proven preventive strategies such as the use of condoms, ART adherence to maintain viral suppression would then be the key challenge for successful TasP implementation.
doi:10.1097/MD.0000000000000902
PMCID: PMC4616551  PMID: 26091454
18.  Measures of condom and safer sex social norms and stigma towards HIV/AIDS among Beijing MSM 
AIDS and behavior  2014;18(6):1068-1074.
Social norms around condom use and safe sex as well as HIV/AIDS stigma are used to identify persons at higher risk for HIV. These measures have been developed and tested in a variety of settings and populations. While efforts have been undertaken to develop context specific measures of these domains among Chinese MSM, the feasibility of using existing measures is unknown. A survey of MSM, based on respondent-driven sampling (RDS), was conducted in Beijing. Existing measures of condom social norms, attitudes towards safer sex and HIV/AIDS stigma were piloted. Internal consistency of all measures was high. As expected higher levels of condom social norms and positive attitudes towards safer sex were associated with condom use. HIV / AIDS stigma and discrimination had a significant relationship with never having an HIV test and lack of discussion of HIV/AIDS with male partners. Correlates of low condom social norms were age, education, employment and resident status. Existing measures of condom social norms, attitudes towards safer sex and HIV/AIDS stigma appear to be appropriate for use among Chinese MSM. Using existing measures as opposed to developing new measures has the potential to expedite investigations into psychosocial correlates of HIV risk behavior.
doi:10.1007/s10461-013-0609-7
PMCID: PMC3962708  PMID: 24057931
men who have sex with men; condom social norms; safer sex; HIV/AIDS stigma; China
19.  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
21.  HIV Testing and Preventive Services Accessibility Among Men Who Have Sex With Men at High Risk of HIV Infection in Beijing, China 
Medicine  2015;94(6):e534.
Abstract
The HIV epidemic among men who have sex with men (MSM) has been increasing at an alarming rate in most areas of China in recent years. Many Chinese MSM still lack sufficient access to HIV prevention services, despite ongoing scale-up of comprehensive HIV testing and intervention services. The purpose of this study was to investigate utilization of HIV testing and prevention services, and related factors that influence the MSM people to access HIV test or other services to prevent HIV among MSM in Beijing, China.
Three successive cross-sectional surveys of MSM were conducted in Beijing from September 2009 to January 2010, September 2010 to January 2011, and September 2011 to January 2012. Demographic and behavioral data were collected and analyzed. Blood samples were tested for HIV and syphilis. Three models were established to analyze factors associated with HIV testing and preventive services.
Of the 1312 participants, prevalence of HIV and syphilis was 7.9% and 15.4%, respectively. Sixty-nine percent ever had an HIV test, 56.2%, 78.7%, and 46.1% received HIV test, free condom/lubricants, and sexually transmitted infection services in the past 12 months (P12M), respectively. MSM with larger social networks and who knew someone infected with HIV were more likely to receive HIV testing and preventive services; lower degrees of stigma and discriminatory attitudes toward HIV/AIDS were positively associated with having an HIV test, whereas unprotected anal intercourse in the past 6 months (P6M) was associated with less preventive services participation. The most reported barriers to HIV testing were fear of testing HIV positive (79.3%) and perceiving no risk for HIV (75.4%). Almost all participants felt that ensuring confidentiality would encourage more MSM to have an HIV test. The two main reasons for not seeking HIV test was not knowing where to go for a test (63.2%) and perceiving low risk of HIV infection (55.1%).
Given a high prevalence of HIV, syphilis, and risky behaviors and a relatively low HIV testing rate among MSM in Beijing, more efforts are urgently needed to address barriers to HIV testing and improve accessibility of prevention services.
doi:10.1097/MD.0000000000000534
PMCID: PMC4602732  PMID: 25674755
22.  HIV-Testing Behavior and Associated Factors Among MSM in Chongqing, China 
Medicine  2014;93(27):e124.
Abstract
The high and climbing human immunodeficiency virus (HIV) rates among Chinese men who have sex with men (MSM) bring huge pressure and challenge to acquired immune deficiency syndrome response work in China. This study examined HIV-testing behavior and describes the characteristics of recently tested MSM in Chongqing to address targeting HIV prevention interventions.
Two consecutive cross-sectional surveys were conducted among Chongqing MSM using respondent-driven sampling in 2009 and 2010. Information was collected regarding details on demographic characteristics, sexual practices with male and female partners, and HIV-testing experiences. Univariate and multivariate logistic regression analyses were performed to identify factors independently associated with recent HIV testing.
The final sample size included in our analyses was 992. The overall HIV prevalence was 13.4%, and HIV prevalence increased significantly from 11.6% in 2009 to 15.4% in 2010 (P = 0.08). The overall rate of HIV testing in the past 12 months was 44.6%, and the self-reported rates decreased significantly from 47.8% in 2009 to 41.1% in 2010 (P = 0.03). Factors independently associated with recent HIV testing included living in Chongqing >1 year (adjusted odds ratio [AOR] 1.8, 95% confidence interval [CI] 1.1–2.9), the age of most recent male partner ≤25 (AOR 1.5, 95% CI 1.1–2.1), not having unprotected insertive anal sex with most recent male partner in the past 6 months (AOR 1.5, 95% CI 1.1–2.0), disclosing HIV status to most recent male partner (AOR 2.8, 95% CI 2.0–3.8), and holding lower level of HIV-related stigma (AOR 1.1 per scale point, 95% CI 1.0–1.1).
The extremely high HIV prevalence and low annual testing level put MSM at high risk of HIV infection and transmission, and it is a priority to promote regular HIV testing among this group in order to control the spread of HIV in Chongqing, China.
doi:10.1097/MD.0000000000000124
PMCID: PMC4602788  PMID: 25501047
23.  Acceptance of Male Circumcision Among Male Rural-to-Urban Migrants in Western China 
AIDS Research and Human Retroviruses  2013;29(12):1582-1588.
Abstract
To describe the acceptability of male circumcision (MC) and explore potential factors associated with MC acceptability among male rural-to-urban migrants in western China, a cross-sectional survey of MC acceptability was conducted with 1,904 subjects in three western provinces with high HIV prevalence (Guangxi, Chongqing, and Xinjiang) in China between June 2009 and November 2009. Through face-to-face interviews, the participants completed a self-administered questionnaire about demographics, MC knowledge, willingness and reasons to accept or refuse MC, sexual behaviors, and other psychosocial variables. Factors associated with acceptability of MC were identified by multiple logistic regression analysis. Of the participants (n=1,904), 710 men were willing to accept MC (37.3%); the reasons included promotion of the partners' genital hygiene (54.9%), redundant prepuce or phimosis (43.1%), enhancement of sexual pleasure (40.6%), prevention of penile inflammation or cancer (35.5%), and protection against HIV and sexual transmitted diseases (STDs)(31.1%). A multivariable logistic regression showed that four factors were associated with acceptability of MC, including education level (OR=1.286, 95% CI=1.025∼1.614), redundant prepuce or phimosis (OR=13.751, 95% CI=10.087∼18.745), having one or more circumcised friends (OR=2.468, 95% CI=1.953∼3.119), and having sexual intercourse with a temporary partner in the past year (OR=1.543, 95% CI=1.101∼2.162). Compared with previously published data among the general population in China or worldwide, the acceptability of MC (37.3%) was low among the male rural-to-urban migrants in western China. Nevertheless, appropriate education could greatly improve the acceptability of MC. More public campaigns and health education on MC are needed to increase the rate of MC in China.
doi:10.1089/aid.2013.0156
PMCID: PMC3848437  PMID: 23931654
24.  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
25.  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

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