Bingyu Liang

Pre-Exposure Prophylaxis for the Prevention of HIV Infection in High Risk Populations: A Meta-Analysis of Randomized Controlled Trials

Background Nearly ten randomized controlled trials (RCTs) of pre-exposure prophylaxis (PrEP) have been completed or are ongoing worldwide to evaluate the effectiveness of PrEP in HIV transmission among HIV-uninfected high risk populations. The purpose of this study was to evaluate the role of PrEP to prevent HIV transmission through a Mata-analysis. Methods A comprehensive computerized literature search was carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wan Fang, CNKI and related websites to collect relevant articles (from their establishment date to August 30, 2013). The search terms were “pre-exposure prophylaxis”, “high risk population”, “HIV infection”, “reduction”, “relative risk” and “efficacy”. We included any RCT assessing PrEP for the prevention of HIV infection in high risk populations. Interventions of the studies were continuously daily or intermittent doses of single or compound antiretrovirals (ARVs) before HIV exposure or during HIV exposure. A meta-analysis was conducted using Stata 10.0. A random-effects method was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI) for all studies included. Results Seven RCTs involving 14,804 individuals in high risk populations were eligible for this study. The number of subjects in the experimental groups was 8,195, with HIV infection rate of 2.03%. The number of subjects in the control groups was 6,609, with HIV infection rate of 4.07%. The pooled RR was 0.53 (95% CI = 0.40∼0.71, P<0.001). The re-analyzed pooled RR were 0.61 (95% CI = 0.48∼0.77, P<0.001), 0.49 (95% CI = 0.38∼0.63, P<0.001), respectively, by excluding the largest study or two studies without statistical significance. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 1,022. Conclusion These results show that PrEP is an effective strategy for reducing new HIV infections in high risk populations.

HIV pre-exposure prophylaxis interest among female sex workers in Guangxi, China.

Objectives Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. Methods A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. Results Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. Conclusions Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi.

Application of a Combined Model with Autoregressive Integrated Moving Average (ARIMA) and Generalized Regression Neural Network (GRNN) in Forecasting Hepatitis Incidence in Heng County, China.

Background Hepatitis is a serious public health problem with increasing cases and property damage in Heng County. It is necessary to develop a model to predict the hepatitis epidemic that could be useful for preventing this disease. Methods The autoregressive integrated moving average (ARIMA) model and the generalized regression neural network (GRNN) model were used to fit the incidence data from the Heng County CDC (Center for Disease Control and Prevention) from January 2005 to December 2012. Then, the ARIMA-GRNN hybrid model was developed. The incidence data from January 2013 to December 2013 were used to validate the models. Several parameters, including mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and mean square error (MSE), were used to compare the performance among the three models. Results The morbidity of hepatitis from Jan 2005 to Dec 2012 has seasonal variation and slightly rising trend. The ARIMA(0,1,2)(1,1,1)12 model was the most appropriate one with the residual test showing a white noise sequence. The smoothing factor of the basic GRNN model and the combined model was 1.8 and 0.07, respectively. The four parameters of the hybrid model were lower than those of the two single models in the validation. The parameters values of the GRNN model were the lowest in the fitting of the three models. Conclusions The hybrid ARIMA-GRNN model showed better hepatitis incidence forecasting in Heng County than the single ARIMA model and the basic GRNN model. It is a potential decision-supportive tool for controlling hepatitis in Heng County.

In vivo effects of methamphetamine on HIV-1 replication: A population-based study.

BACKGROUND Although a number of in vitro studies have shown that methamphetamine (METH) can increase HIV-1 replication in human immune cells, a direct link between METH use and HIV-1 pathogenesis remains to be determined among HIV-1 patients. METHODS According to the status of METH use and HIV-1 infection, we enrolled participants and divided them into four groups: METH+HIV+, METH-HIV+, METH+HIV-, and METH-HIV-. HIV viral loads and HIV-1-related cellular factors were measured and compared among different groups. RESULTS A total of 60 participants were enrolled into this study, 15 within each group. HIV viral loads in METH+HIV+ group were significantly higher than those in METH-HIV+ group, while CD4+ T cell counts had an inverse trend between the two groups (p<0.05). METH users or HIV-1 infected patients had lower CCR5+, CXCR4+ percentages in CD4+ T cells than METH-HIV- subjects (p<0.01). However, METH use had little effect on CD3 expression in PBMCs and the levels of MIP-1α, MIP-1β and IL-6 in PBMCs or plasma, which were increased by HIV-1 infection with or without METH. TLR-9 and IFN-α levels in PBMCs of METH users with or without HIV infection were higher than non-METH users (p<0.05). CONCLUSIONS METH use is associated with higher viral loads and lower CD4+ T cell counts in HIV-infected individuals. This finding may be mediated by activation of innate immunity (TLR-9, IFN-α) by METH use.

Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells

Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells. Tunicamycin treatment or HCV infection could induce cellular autophagy, however, MPA also exhibited its inhibitory effect on tunicamycin- or HCV infection-induced autophagy. The expression of three autophagy-related genes, Atg3, Atg5, and Atg7 were identified to be inhibited by MPA treatment. Over-expression of these genes could partly recover HCV replication inhibited by MPA; however, silencing their expression by siRNAs could enhance the inhibitory effect of MPA on HCV. Collectively, these results reveal that suppression of autophagy by MPA plays a role in its anti-HCV activity. Down-regulating the expression of three autophagy-related genes by MPA involves in its antiviral mechanism.

Downregulation of autophagy-related gene ATG5 and GABARAP expression by IFN-λ1 contributes to its anti-HCV activity in human hepatoma cells

ABSTRACT Type‐III interferon (IFN‐&lgr;), the most recently discovered family of IFNs, shares common features with type I IFNs, but also has many distinctive activities. It is not clear that whether IFN‐&lgr; has additional antiviral mechanisms. In this study, we investigated the effects of IFN‐&lgr; on autophagy, a cellular process closely related to hepatitis C virus (HCV) infection in human hepatoma Huh7 cells. Our results showed that IFN‐&lgr;1 treatment inhibit autophagic activity in Huh7 cells, as evidenced by the decreased expression of microtubule‐associated protein 1 light chain 3B (LC3B)‐II and conversion of LC3B‐I to LC3B‐II, decreased formation of GFP‐LC3 puncta and accumulation of autophagosomes. IFN‐&lgr;1 could also inhibit HCV‐induced or tunicamycin (a known inducer of autophagy with similar mechanism to HCV infection) ‐induced LC3B‐II expression and autophagosome formation. Through PCR array, real time RT PCR, and western blot, two autophagy‐related genes, ATG5 and GABARAP, were identified and verified to be down‐regulated by IFN‐&lgr;1 treatment, either in HCV‐uninfected Huh7 cells or in HCV JFH‐1‐infected cells. Overexpression of ATG5 and/or GABARAP could partly recover the IFN‐&lgr;1‐inhibited HCV replication. Mechanism research demonstrated that IFN‐&lgr;1 could induce the expression of miR‐181a and miR‐214 (targeting ATG5 and GABARAP respectively), by which down‐regulates ATG5 and GABARAP expression. Taken together, our results indicate that suppression of the autophagy response by IFN‐&lgr;1 contributes to IFN‐&lgr;1 anti‐HCV activity. The results also provide a theoretical basis for improving the effectiveness of IFN treatment of HCV infection through inhibition of the HCV‐induced autophagy response. HIGHLIGHTSIFN‐&lgr;1 suppresses cellular autophagy in Huh7 cells, which contributes to IFN‐&lgr;1 anti‐HCV activity.IFN‐&lgr;1 induces the expression of miR‐181a and miR‐214, by which down‐regulates expression of ATG5 and GABARAP.Type I IFN (IFN‐&agr;2a) has little effect on autophagy in Huh7 cells.

Short Communication: HIV-1 Infection Suppresses Circulating Viral Restriction microRNAs.

MicroRNAs (miRNAs) participate in host innate immunity against HIV-1 infection. We examined the impact of HIV-1 infection on viral restriction miRNAs in plasma of HIV-1-infected subjects. HIV-1-infected subjects had significantly lower plasma levels of HIV-1 restriction miRNAs (miRs-29a, -29b, -125b, -223, -198, and -382) than control subjects. Further in vitro studies showed that HIV-1 infection of macrophages suppressed production of the extracellular miRs-29b, -125b, and -223. These data demonstrate the compelling evidence that HIV-1 infection impairs host innate immunity by inhibiting antiviral miRNAs, which provide a possible mechanism for HIV-1 persistence in the host.

Accuracy of rapid diagnosis of Talaromyces marneffei: A systematic review and meta-analysis

Background To examine the accuracy of Rapid Diagnosis of Talaromyces marneffei (RDTM) in order to improve diagnosis and treatment for clinical measures and reduce the mortality due to associated infections. Methods In this systematic review and meta-analysis, we screened PubMed, Ovid (Cochrane library) and Web of Science, Chinese database CNKI and Wanfang for articles published between 1956 and December, 2017. Data were taken from cross-sectional studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with T. marneffei and a control cohort or a cohort with standard fungus culture. Data were extracted by two authors and checked by three for accuracy. For quality assessment, modified QUADAS-2 criteria were used. Results The 26 included diagnostic studies enrolled 5,594 objectives in 632 patients with T. marneffei infections and 2,612 negative controls between 1996 and 2017 in Thailand, Vietnam and China. The total combined sensitivity and specificity of rapid diagnosis of T. marneffei was 0.82 (95% CI: 0.68–0.90) and 0.99 (95% CI: 0.98–1.00). According to the experimental method, the included studies can be divided into three subgroups, including PCR-based, ELISA-based and others. The results showed these three subgroups had a highly pooled specificity of 1.00 (95% CI: 0.99–1.00), 0.99 (0.98–1.00) and 0.97 (95% CI: 0.91–1.00), respectively, while combined sensitivity was 0.84 (95% CI: 0.37–0.98), 0.82 (95% CI: 0.64–0.92) and 0.77 (95% CI: 0.54–0.91), respectively. Conclusions Although serological methods with a high specificity is essential for potential rapid diagnostic, false-negative results can be obtained in the serum samples, there is no suitable rapid serological test to refer to as is the case with TM infection.

Impact of Educational Interventions on Acceptance and Uptake of Male Circumcision in the General Population of Western China: A Multicenter Cohort Study

To compare different intervention models for promoting male circumcision (MC) to prevent HIV transmission in Western China. A total of 1690 male participants from multiple study sites were cluster randomly allocated to three-stage (Model A), two-stage (Model B), and one-stage (Model C) educational interventions. In all three interventions models, knowledge about MC significantly increased and the reported willingness to accept MC increased to 52.6% (255/485), 67.0% (353/527), and 45.5% (219/481) after intervention, respectively (P < 0.05). Rate of MC surgery uptake was highest (23.7%; 115/485) among those who received Model A intervention, compared to those who received Model B (17.1%; 90/527) or Model C (9.4%; 45/481) interventions (P < 0.05). Multivariable Cox regression analysis identified that Model A or Model B had twice the effect of Model C on MC uptake, with relative risks of 2.4 (95%CI, 1.5–3.8) and 2.2 (95%CI, 1.3–3.6), respectively. Model B was the most effective model for improving participants’ willingness to accept MC, while Model A was most successful at increasing uptake of MC surgery. Self-reported attitude towards MC uptake was not strongly correlated with actual behavior in this study focusing on the general male population in Western China.

Acceptability of Male Circumcision among College Students in Medical Universities in Western China: A Cross-Sectional Study

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.