Administration of mRNA-Nanomedicine-Augmented Calvarial Defect Healing via Endochondral Ossification.

Large-area craniofacial defects remain a challenge for orthopaedists, hastening the need to develop a facile and safe tissue engineering strategy; osteoconductive material and a combination of optimal growth factors and microenvironment should be considered. Faced with the unmet need, we propose that abundant cytokines and chemokines can be secreted from the bone defect, provoking the infiltration of endogenous stem cells to assist bone regeneration. We can provide a potent mRNA medicine cocktail to promptly initiate the formation of bone templates, osteogenesis, and subsequent bone matrix deposition via endochondral ossification, which may retard rapid fibroblast infiltration and prevent the formation of atrophic non-union. We explored the mutual interaction of BMP2 and TGFß3 mRNA, both potent chondrogenic factors, on inducing endochondral ossification; examined the influence of in vitro the transcribed polyA tail length on mRNA stability; prepared mRNA nanomedicine using a PEGylated polyaspartamide block copolymer loaded in a gelatin sponge and grafted in a critical-sized calvarial defect; and evaluated bone regeneration using histological and µCT examination. The BMP2 and TGFß3 composite mRNA nanomedicine resulted in over 10-fold new bone volume (BV) regeneration in 8 weeks than the BMP2 mRNA nanomedicine administration alone, demonstrating that the TGFß3 mRNA nanomedicine synergistically enhances the bone's formation capability, which is induced by BMP2 mRNA nanomedicine. Our data demonstrated that mRNA-medicine-mediated endochondral ossification provides an alternative cell-free tissue engineering methodology for guiding craniofacial defect healing.

A Randomized Clinical Trial of 1-Dose vs Accelerated 2-Dose Schedule for Hepatitis A Virus (HAV) Revaccination Among People With Human Immunodeficiency Virus Who Were Nonresponders or Had Seroreversion After Primary HAV Vaccination.

BACKGROUND: For people with human immunodeficiency virus (PWH) who have no serological responses to their primary hepatitis A virus (HAV) vaccination or have seroreversion after successful primary vaccination, the optimal revaccination strategy remains unclear. METHODS: In this open-label, randomized clinical trial, PWH who tested negative for anti-HAV antibodies after receiving a standard 2-dose series of primary HAV vaccination were enrolled and assigned in a 1:1 ratio to receive either 1 dose (the 1-dose group) or 2 doses of HAV vaccine administered 4 weeks apart (the 2-dose group). Serological response rates and anti-HAV antibody titers were compared at weeks 24 and 48. RESULTS: Of the 153 participants (77 in the 1-dose group and 76 in the 2-dose group), the overall serological response rates at week 48 after revaccination were similar between the 2 groups (2- vs 1-dose, 80.2% vs 71.4%, P = .20). However, anti-HAV antibody titers were consistently higher in the 2-dose group than in the 1-dose group. In subgroup analysis, PWH who were nonresponders to primary HAV vaccination were significantly more likely to mount a serological response after 2-dose HAV revaccination (68.4% vs 44.1%, P = .038). No severe adverse events were reported throughout the study. CONCLUSIONS: Two-dose HAV revaccination administered 4 weeks apart yielded similar serological responses as 1-dose revaccination among PWH who were nonresponders or had seroreversion after primary HAV vaccination. The 2-dose revaccination schedule generated significantly higher anti-HAV antibody titers and was more likely to elicit serological responses at week 48 among PWH who were nonresponders to primary HAV vaccination. Clinical Trials Registration. NCT03855176.

Integration of Adenylate Kinase 1 with Its Peptide Conformational Imprint.

In the present study, molecularly imprinted polymers (MIPs) were used as a tool to grasp a targeted α-helix or ß-sheet of protein. During the fabrication of the hinge-mediated MIPs, elegant cavities took shape in a special solvent on quartz crystal microbalance (QCM) chips. The cavities, which were complementary to the protein secondary structure, acted as a peptide conformational imprint (PCI) for adenylate kinase 1 (AK1). We established a promising strategy to examine the binding affinities of human AK1 in conformational dynamics using the peptide-imprinting method. Moreover, when bound to AK1, PCIs are able to gain stability and tend to maintain higher catalytic activities than free AK1. Such designed fixations not only act on hinges as accelerators; some are also inhibitors. One example of PCI inhibition of AK1 catalytic activity takes place when PCI integrates with an AK19-23 ß-sheet. In addition, conformation ties, a general MIP method derived from random-coil AK1133-144 in buffer/acetonitrile, are also inhibitors. The inhibition may be due to the need for this peptide to execute conformational transition during catalysis.

Non-opioid recreational drug use and a prolonged HIV outbreak among men who have sex with men in Taiwan: An incident case-control study, 2006-2015.

BACKGROUND/PURPOSE: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak. METHODS: We conducted a retrospective case-control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors. RESULTS: From a total of 15,305 MSM client visits during 2006-2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6-7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006-2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps < 0.05). CONCLUSION: Non-opioid recreational drugs use is associated with incident HIV infection in this prolonged HIV outbreak. There is an urgent need to formulate an effective public health response to mitigate the risk.

Deviation of Trypsin Activity Using Peptide Conformational Imprints.

In this study, a methodology utilizing peptide conformational imprints (PCIs) as a tool to specifically immobilize porcine pancreatic alpha-trypsin (PPT) at a targeted position is demonstrated. Owing to the fabrication of segment-mediated PCIs on the magnetic particles (PCIMPs), elegant cavities complementary to the PPT structure are constructed. Based on the sequence on targeted PPT, the individual region of the enzyme is trapped with different template-derived PCIMPs to show certain types of inhibition. Upon hydrolysis, N-benzoyl-L-arginine ethyl ester (BAEE) is employed to assess the hydrolytic activity of PCIMPs bound to the trypsin using high-performance liquid chromatography (HPLC) analysis. Further, the kinetic data of four different PCIMPs are compared. As a result, the PCIMPs presented non-competitive inhibition toward trypsin, according to the Lineweaver-Burk plot. Further, the kinetic analysis confirmed that the best parameters of PPT/PCIMPs 233-245+G were Vmax = 1.47 × 10-3 mM s-1, Km = 0.42 mM, kcat = 1.16 s-1, and kcat/Km = 2.79 mM-1 s-1. As PPT is bound tightly to the correct position, its catalytic activities could be sustained. Additionally, our findings stated that the immobilized PPT could maintain stable activity even after four successive cycles.

Sensing HIV Protease and Its Inhibitor Using "Helical Epitope"-Imprinted Polymers.

A helical epitope-peptide (lle85-Gly94) was selected from the α-helix structure of the HIV protease (PR) as the template, which represents an intricate interplay between structure conformation and dimerization. The peptide template was mixed with water, trifluoroethanol (TFE), and acetonitrile (ACN) at a certain ratio to enlarge the helical conformation in the solution for the fabrication of helical epitope-mediated molecularly imprinted polymers (HEMIPs) on a quartz crystal microbalance (QCM) chip. The template molecules were then removed under equilibrium batch rebinding conditions involving 5% acetic acid/water. The resulting HEMIPs chip exhibited a high affinity toward template peptide HIV PR85-94, His-tagged HIV PR, and HIV PR, with dissociation constants (Kd) as 160, 43.3, and 78.5 pM, respectively. The detection limit of the developed HIV PR85-94 QCM sensor is 0.1 ng/mL. The HEMIPs chip exhibited a high affinity and selectivity to bind HIV PR and subsequently to an inhibitor of HIV PR (nelfinavir). The HIV PR binding site was properly oriented on the HEMIPs-chip to develop a HIV PR/HEMIPs chip, which can effectively bind nelfinavir to establish a sandwich assay. The nelfinavir then attached to the HIV PR/HEMIPs chip, which can be easily removed involving 0.8% acetic acid/water. Therefore, HIV PR/HEMIPs chip can be useful to screen for other HIV PR inhibitors. This technique may improve drug targeting for HIV therapy and also strengthen investigations into other virus assays.

Awareness and willingness towards pre-exposure prophylaxis against HIV infection among individuals seeking voluntary counselling and testing for HIV in Taiwan: a cross-sectional questionnaire survey.

OBJECTIVES: We aimed to investigate the awareness and willingness towards pre-exposure prophylaxis (PrEP) among individuals seeking voluntary counselling and testing (VCT) for HIV in Taiwan, where PrEP is currently not reimbursed by the insurance. METHODS: Between April and October 2016, a questionnaire interview was conducted among VCT clients to inquire about the attitudes towards PrEP against HIV infection. Multivariate logistic regression analysis was performed to identify the associated factors with willingness to initiate PrEP. RESULTS: During the 6-month period, 1173 VCT clients (99.8%) completed the interviews, with 67.4% being homosexual or bisexual male. While 67.2% of the clients knew of postexposure prophylaxis, 40.2% heard of PrEP. Overall, 546 clients (46.5%) were willing to initiate PrEP and 89.5% of them would choose event-driven PrEP. In multivariate analysis, male gender (OR 1.796; 95% CI 1.165 to 2.768), full-time job (OR 1.354; 95% CI 1.052 to 1.742), one-night stand (OR 1.374; 95% CI 1.043 to 1.810), having casual sex partners within 3 months (OR 1.329; 95% CI 1.031 to 1.714), condomless anal sex (OR 1.405; 95% CI 1.122 to 1.878) and ever having chemsex or attending a drug party in the past 1 year (OR 2.571; 95% CI 1.541 to 4.287), regular screening for HIV infection (OR 1.321; 95% CI 1.021 to 1.711) and knowledge of PrEP (OR 1.504; 95% CI, 1.159 to 1.953) were associated with willingness to initiate PrEP. CONCLUSIONS: Understanding the willingness to initiate PrEP against HIV among the VCT clients in Taiwan, which was associated with male gender, risky sexual behaviours and awareness of PrEP, will help inform the implementation of PrEP programme.

Increasing incidence of recent hepatitis C virus infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan.

OBJECTIVES: The incidence of hepatitis C virus (HCV) infection among HIV-negative men who have sex with men (MSM) is rarely investigated in the Asia-Pacific region. We aimed to estimate the incidence rate of and factors associated with recent HCV infection among the clients seeking voluntary counselling and testing (VCT) services for HIV in Taiwan. METHODS: During 2006-2013, 12 143 clients sought VCT services for HIV. Clients with subsequent follow-up tests at an interval of 6 months or longer were included to estimate the incidence rate of HCV seroconversion. Phylogenetic analysis of HCV sequences from VCT clients and HIV-positive patients was performed. RESULTS: The overall HCV seroprevalence at baseline was 0.3%. Of 2150 clients testing negative for anti-HCV antibody at baseline with a total of 5074.99 person-years of follow-up (PYFU), 17 (0.8%) developed HCV seroconversion, leading to an overall incidence rate of 3.35 per 1000 PYFU (95% CI 1.76 to 4.94), which increased from 2.28 (95% CI 0.05 to 4.51) in 2006-2009, to 3.33 (95% CI 0.86 to 5.80) in 2010 to 2011 and 4.94 per 1000 PYFU (95% CI 0.99 to 8.99) in 2012-2013; the incidence of early syphilis increased from 11.91 to 13.28 and 31.78 per 1000 PYFU in the three corresponding periods. In multivariate analysis, having HIV-positive partners (adjusted HR (AHR) =3.756; 95%CI 1.180 to 11.955) and developing a rapid plasma reagin titre of 4 or greater (AHR=9.978; 95% CI 1.550 to 64.233) were significantly associated with HCV seroconversion. CONCLUSIONS: An increasing trend of recent HCV infection occurs among individuals seeking VCT services in Taiwan. Having HIV-positive partners and having syphilis are independently associated with recent HCV seroconversion.

Incidence of recent HCV infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan.

INTRODUCTION: The incidence of recent hepatitis C virus infection (HCV) infection has been noted to be increasing among men who have sex with men (MSM), especially those with HIV infection, in several resource-rich settings. In Taiwan, the incidence of recent HCV infection increased from 0 in 1994-2000, 2.29 in 2001-2005 to 10.13 per 1000 person-years of follow-up (PYFU) in 2006-2010. In this study, we aimed to estimate the incidence rate of recent HCV infection among those individuals who sought voluntary counselling and testing (VCT) service at a University Hospital. METHODS: Between May 2006 and December 2013, 18,246 tests for HIV antibody were performed among 12,143 individuals at the VCT services. A total of 2157 clients without HIV or HCV infection at baseline were included for estimation of incidence rate of recent HCV infection. Antibodies to HCV were determined with a third-generation enzyme immunoassay. A nested case-control study with four matched controls without HCV seroconversion for one HCV seroconverter was conducted to investigate the factors associated with recent HCV infection. Phylogenetic analysis was performed among the HCV strains obtained from VCT clients and patients coinfected with HIV and HCV between 2006 and 2013. RESULTS: During the study period, 2157 clients received a total of 8260 tests. The HCV seroprevalence at baseline was 0.3%. Of the 2150 HCV-negative clients who contributed 5074.99 PYFU, 17 developed HCV seroconversion (incidence rate, 3.35 per 1000 PYFU; 95% CI, 1.76-4.94); the rate increased from 2.28 per 1000 PYFU (95% CI, 0.05-4.51) in 2006-2009, to 3.33 per 1000 PYFU (95% CI, 0.86-5.80) in 2010-2011, to 4.94 per 1000 PYFU (95% CI, 0.99-8.99) in 2012-2013. In case-control study, HCV seroconverters were more likely to have HIV-infected partners, recent syphilis and a Rapid Plasma Reagin (RPR) titre of 4 or greater. In multivariate analysis, having HIV-infected partners remained as the only independent associated factors with HCV seroconversion (AOR, 6.931; 95% CI, 1.064-45.163). Phylogenetic analysis revealed transmission pairs and clusters, with most clustered sequences derived from MSM. CONCLUSIONS: Similar to the observation among HIV-infected patients who are not IDUs, increasing trends of recent HCV infection also occur among the individuals who sought VCT services in Taiwan. Having HIV-infected partners is independently associated with recent HCV seroconversion.

Seroincidence of HIV and prevalence of transmitted drug resistance of HIV-1 strains among persons seeking voluntary counselling and testing in Taiwan.

INTRODUCTION: The total case number of persons who are newly diagnosed with HIV continues to increase in Taiwan and men who have sex with men (MSM) have re-emerged as the leading risk group for HIV transmission. In this study, we aimed to estimate the incidence rate of HIV infection among those individuals who sought voluntary counselling and testing (VCT) service at a university hospital. METHODS: Between 1 April, 2006 and 31 December, 2013, 18,246 tests for HIV antibody were performed among 12143 individuals at the VCT service. A total of 2157 individuals who tested negative for anti-HIV antibody had subsequent follow-up tests at the same VCT service, which composed the study population for estimation of incidence rate of recent HIV infection. The BED assays were used to identify recent HIV infections that occurred within the previous six months before seeking VCT service. RESULTS: During the 6.5-year study period, 647 individuals were diagnosed as being HIV-positive, with an overall HIV seroprevalence of 3.55% (95% CI 3.27-3.82). The overall incidence rate of HIV infection was estimated 4.13 per 100 person-years of follow-up (95% CI 3.67-4.69 per 100 person-years of follow-up). MSM had an estimated 10-fold higher seroprevalence and seroincidence of HIV than heterosexuals. Of 647 clients testing positive for HIV, 603 clients were MSM (93.2%) and 477 patients (70.8%) subsequently sought HIV care at the hospital; 226 (47.4%) were diagnosed as having recent HIV infections by the BED assay, while 244 (51.2%) long-term infection and 7 without data by the BED assay. Of those patients, 173 (75.6%) and 178 patients (73.0%) with recent HIV infection and long-term infection had data of transmitted drug resistance mutations, respectively. The prevalence of transmitted drug resistance mutations to any class of antiretroviral therapy was 9.0% and 10.6% (p=0.68), respectively, of the HIV-1 strains from the patients with recent HIV infection and long-term infection, respectively. CONCLUSIONS: The seroincidence rate of HIV among persons seeking VCT was estimated 4.13 per 100 person-years of follow-up. The prevalence of transmitted drug resistance to any class of antiretroviral agents was similar between those who were recently infected with HIV and those who had long-term infection in Taiwan.

Seroprevalence of hepatitis B virus among adults at high risk for HIV transmission two decades after implementation of nationwide hepatitis B virus vaccination program in Taiwan.

BACKGROUND: Seroprevalence of hepatitis B virus (HBV) after implementation of universal neonatal HBV vaccination and catch-up vaccination programs remains rarely investigated among the adults who were born in the vaccination era (in or after 1986) and engaged in high-risk sexual behaviors. MATERIALS AND METHODS: Between 2006 and 2012, we determined HBV surface antigen ([HBsAg), anti-HBs, and HBV core antibody (anti-HBc), hepatitis C virus antibody (anti-HCV) and rapid plasma reagin titers among HIV-infected men who have sex with men (MSM) born during 1984-1985 (Group I: 244 persons) and those born in or after 1986 (Group II: 523), and HIV-uninfected MSM (Group III: 377) and heterosexuals (Group IV: 217) born in or after 1986. Prevalence and incidence of HBV infection were estimated and multivariate analysis was performed to identify factors associated with HBsAg positivity. RESULTS: Compared with Group I, Groups II-IV had a significantly lower prevalence of HBsAg positivity (7.8% vs 3.7%, 2.4%, and 3.2%, respectively); and the prevalence of anti-HBc positivity was also lower for Groups III and IV (30.3% vs. 19.6%, and 18.0%, respectively), but no difference was observed between Groups I and II (30.3% vs. 26.3%). In multivariate analysis, HBsAg positivity was significantly associated with syphilis (adjusted odds ratio, 2.990; 95% confidence interval, 1.502-5.953) and anti-HCV positivity (adjusted odds ratio, 3.402; 95% confidence interval, 1.091-10.614). In subjects of Group II with all-negative HBV markers at baseline, the incidence rate of HBsAg seroconversion was 0.486 episodes per 100 person-years; and for those who received combination antiretroviral therapy containing lamivudine and/or tenofovir, none developed HBsAg seroconversion during the follow-up. CONCLUSIONS: Among the adults who were born in or after 1986 and engaged in high-risk sexual behaviors in Taiwan, neonatal HBV vaccination and catch-up vaccination programs conferred long-term protection against HBsAg seroconversion and HBsAg positivity was associated with syphilis and anti-HCV positivity.

Associated factors with and genotypes of Chlamydia trachomatis infection among clients seeking voluntary counseling and testing for HIV infection in Taiwan.

BACKGROUND/PURPOSE: This study aimed to investigate the factors associated with Chlamydia trachomatis infection and the genotype distribution of the strains among the clients seeking voluntary counseling and testing (VCT) for human immunodeficiency virus (HIV) in Taiwan. METHODS: The VCT clients completed an anonymous self-administered questionnaire interview to inquire into the risks for sexually transmitted diseases, followed by providing a 10-mL first-catch urine specimen to detect C. trachomatis with the use of polymerase-chain-reaction assays. The genotyping of C. trachomatis strains was performed by sequencing of omp1 gene. A case-control study was performed to identify factors associated with chlamydial infection. RESULTS: From 2008 to 2011, 140 (4.2%) of the 3323 VCT clients tested positive for C. trachomatis by polymerase chain reaction assays of urine specimens. Compared with 280 control individuals without C. trachomatis infection, cases were more likely to be female (adjusted odds ratio, 3.28; 95% confidence interval, 1.56-6.90) and to report dysuria or urethral discharge (adjusted odds ratio, 2.57; 95% confidence interval, 1.44-4.61). Infections with genotypes Da and G were significantly more common in male than female individuals (genotype Da, 22.2% vs. 0%; and genotype G, 24.4% vs. 3.3%) and in men who have sex with men than heterosexuals (genotype Da, 22.2% vs. 0%; and genotype G, 24.4% vs. 3.3%). CONCLUSION: Among the VCT clients in Taiwan, female sex and presence of urethral symptoms were associated with C. trachomatis infection of the genitourinary tract. Homosexual male clients were more likely to be infected with genotypes Da and G than heterosexual clients were.

Seroepidemiology of novel influenza A (H1N1) infection among HIV-infected patients in the era of highly active antiretroviral therapy.

BACKGROUND: The seroprevalence and seroincidence of novel influenza A infection among HIV-infected patients, who were believed to have more severe outcomes than healthy individuals, are rarely investigated in the era of highly active antiretroviral therapy (HAART). Our aim was to determine the seroprevalence and seroincidence of novel influenza A infection among HIV-infected patients in Taiwan. METHODS: Between September and November 2009, before the implementation of a nationwide vaccination for novel influenza A in Taiwan, 931 HIV-infected patients and 566 persons seeking voluntary counseling and testing (VCT) for HIV infection at our university hospital were enrolled in this study. Antibody responses to novel influenza A were determined using a hemagglutination-inhibition (HI) assay. RESULTS: HIV-infected patients had a significantly lower seroprevalence of novel influenza A infection than VCT clients (14.7% vs. 33.9%, p < 0.001). The seroincidence of novel influenza A infection among HIV-infected patients was 9.4% (95% confidence interval [CI]: 7.6-11.4). On the multivariate analysis, heterosexual (odds ratio [OR]: 1.89; 95% CI: 1.105-3.227) and baseline HI titer (OR: 1.02; 95% CI: 1.001-1.038) were significantly associated with seroconversion to novel influenza A virus. CONCLUSION: HIV-infected patients demonstrated a lower seroprevalence of novel influenza A infection than HIV-uninfected patients in Taiwan in the HAART era. Among HIV-infected patients, seroconversion to novel influenza A virus, which was infrequent during the 2009 influenza epidemic, was associated with heterosexual behavior and baseline HI titer.

Comparative effectiveness of two doses versus three doses of hepatitis A vaccine in human immunodeficiency virus-infected and -uninfected men who have sex with men.

UNLABELLED: The purpose of this prospective cohort study was to compare the serologic response between human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) receiving two and three doses of hepatitis A virus (HAV) vaccine and HIV-uninfected MSM receiving two doses of HAV vaccine. Between June 2009 and December 2010, 582 MSM aged 18 to 40 years who were seronegative for HAV were enrolled in the study. HIV-infected MSM received either two doses of HAV vaccine (1,440 enzyme-linked immunosorbent assay units) (n = 140) with the second dose given at week 24 or three doses (n = 225) with the second and third dose given at weeks 4 and 24, respectively, while HIV-uninfected MSM (n = 217) received two doses. The primary endpoint was seroconversion at week 48. The geometric mean concentration (GMC) of anti-HAV antibody was determined at weeks 48 and 72. At week 48, the seroconversion rate was 75.7%, 77.8%, and 88.5% in intention-to-treat analysis for two-dose HIV-infected, three-dose HIV-infected, and two-dose HIV-uninfected MSM, respectively. The GMC of anti-HAV antibody at week 48 for three-dose HIV-infected MSM (2.29 ± 0.73 log10 mIU/mL) was significantly higher than that for two-dose HIV-infected MSM (1.94 ± 0.66; P < 0.01), but was lower than HIV-uninfected MSM (2.49 ± 0.42; P < 0.01). Multivariate analysis revealed higher CD4 counts (adjusted odds ratio [AOR] for per 50 cells/µL increase, 1.13; 95% confidence interval [CI], 1.05-1.21) and undetectable plasma HIV RNA load (AOR, 1.90; 95% CI, 1.10-3.28) before HAV vaccination were predictive of seroconversion in HIV-infected patients. CONCLUSION: Serologic response rate to three and two doses of HAV vaccine was similar in HIV-infected MSM, which was lower than that in HIV-uninfected MSM receiving two doses. HAV vaccination in HIV-infected patients with a higher CD4 count and suppression of HIV replication increased the seroconversion rate.

Seroprevalence of hepatitis virus infection in men who have sex with men aged 18-40 years in Taiwan.

BACKGROUND/PURPOSE: Men who have sex with men (MSM) are at increased risk for hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections than the general population. Comparisons of the seroprevalence rates of these hepatitis viruses between HIV-positive and HIV-negative MSM are rarely performed in Taiwan. METHODS: Between January 2009 and June 2010, data on the serologies for HAV, HBV, and HCV were collected from two groups of patients: HIV-negative MSM, aged 18-40 years, who sought voluntary counseling and testing (VCT) for HIV infection, and HIV-positive MSM of the same age group who sought HIV care at the National Taiwan University Hospital. Both groups of patients were also tested for syphilis. RESULTS: During the 18-month study period, 690 HIV-negative MSM and 438 HIV-positive MSM were enrolled and tested for anti-HAV antibody, HBV surface antigen (HBsAg), hepatitis B core antibody (anti-HBc antibody), and anti-HCV antibody. HIV-positive MSM were older than HIV-negative MSM (30.5 ± 5.4 vs. 25.8 ± 4.7 years, p < 0.01). For HIV-positive MSM, the mean CD4 lymphocyte count was 477.6 ± 230.0 cells/µL and 46% of them had undetectable plasma HIV RNA load (< 40 copies/mL by reverse transcription-polymerase chain reaction assay). The overall seroprevalence rates of HAV, HBsAg, and HCV in HIV-positive MSM were 15.1%, 16.4%, and 5.5%, respectively, while in HIV-negative MSM, they were 7.4%, 6.2%, and 0.4%, respectively. In the multivariate analysis, age was significantly associated with seropositivity for HAV (OR [per one age group increase]: 1.96; 95% CI: 1.6-2.5), HBsAg (OR: 2.02; 95% CI: 1.6-2.6), anti-HBc (OR: 2.68; 95% CI: 2.3-3.2), anti-HCV (OR: 1.67; 95% CI: 1.0-2.7), and anti-HBs (OR: 1.25; 95% CI: 1.0-1.5). HIV infection was associated with seropositivity for HBsAg (OR: 1.73; 95% CI: 1.1-2.7), anti-HBc (OR: 2.44; 95% CI: 1.8-3.3), HCV (OR: 8.91; 95% CI: 2.5-31.4), and syphilis (OR: 11.21; 95% CI: 6.7-18.9). CONCLUSION: HIV-positive MSM have a higher seroprevalence rate of HBV and HCV infection than HIV-negative MSM in Taiwan. Vaccination and safe-sex counseling should be provided to prevent the transmission of hepatitis viruses among MSM who may be engaged in high-risk behaviors.

Impact of vaccination with seven-valent pneumococcal conjugate vaccine on virologic and immunologic outcomes among HIV-infected adult patients in the era of highly active antiretroviral therapy.

BACKGROUND/PURPOSE: Pneumococcal polysaccharide vaccination may be associated with adverse outcomes in HIV-infected individuals who did not receive highly active antiretroviral therapy (HAART). Our aim was to evaluate the impact of vaccination with seven-valent pneumococcal conjugate vaccine (PCV) on the short-term clinical, virologic, and immunologic outcomes among HIV-infected adult patients in the HAART era. METHODS: A total of 429 HIV-infected adult patients were enrolled from October 2008 to March 2010: 213 received two doses of seven-valent PCV given at a 4-week interval and 216 received one dose. All patients were given 1-week diary to record any discomfort after vaccination. Data of serial CD4 and plasma HIV RNA load measurements were recorded. RESULTS: Of the 429 patients with a mean CD4 count of 305 cells/µL, 289 (67.4%) were receiving HAART and 175 (40.8%) had plasma HIV RNA load <40 copies/mL at vaccination. Of the 396 patients (92.3%) who returned the diary, injection site soreness (24.0%) and pain (10.4%) were the most commonly reported adverse effects. After 3-4 months of vaccination, CD4 count increased by 40 cells/µL in 278 patients (68.2%) who continued HAART, compared with a decrease of 38 cells/µL in 131 patients (31.8%) who were not on HAART (p < 0.001), while the respective change in plasma HIV RNA load was 0.8 versus 0.2 log(10) copies/mL (p = 0.09). One patient died, two developed opportunistic infections, and one developed pneumococcal pneumonia following vaccination. CONCLUSION: Vaccination with seven-valent PCV among HIV-infected patients is generally safe, which has no detrimental effect on CD4 count and plasma HIV RNA load in patients receiving HAART. (ClinicalTrials.gov number, NCT00885628).

Maximising the potential of voluntary counselling and testing for HIV: sexually transmitted infections and HIV epidemiology in a population testing for HIV and its implications for practice.

OBJECTIVES: This study aimed to describe the epidemiology of HIV infection and sexually transmitted infections (STIs) among persons who attended voluntary counselling and testing (VCT) service for HIV and to assess whether the VCT programme reached the right population at risk in Taiwan. METHODS: From 2006 to 2010, questionnaire interview, integrated pretesting and post-testing counselling, followed by serological tests for HIV, Treponema pallidum and Entamoeba histolytica were performed for all VCT clients; additional tests for Chlamydia trachomatis and Neisseria gonorrhoeae using PCR assays of urine specimens were provided when the assays became available in two periods. RESULTS: During the study period, 10 198 VCT attendances occurred in 6863 clients, in whom 1685 (24.6%) had re-attendances. Male clients, men who have sex with men and clients with one-night stand and casual sexual partners were more likely to re-attend VCT service in the next 12 months. The overall STI prevalence was 3.5% for HIV infection, 2.2% syphilis, 1.0% amoebiasis, 4.7% chlamydia and 0.7% gonorrhoea. In logistic regression model, men who have sex with men were consistently independently associated with HIV infection, syphilis and amoebiasis. Among the repeaters, the incidence rate of HIV infection and syphilis was 3.4 and 1.6 per 100 person-years of follow-up, respectively. In Cox regression analysis, clients who used illicit non-injection recreational drugs and who practiced unprotected anal sex were at significantly higher risk of acquiring HIV infection and syphilis. CONCLUSIONS: With higher rates of re-attendances and STIs, the VCT programme reached the population most at risk for HIV and STIs compared with other screening programmes in Taiwan. The potential of VCT programme can be maximised in the prevention and control of HIV infection and STIs by providing tests for more STIs and counselling to avoid use of recreational drugs and to promote safe sex.

Incidence of acute pancreatitis in human immunodeficiency virus-positive patients with hypertriglyceridemia: is it really high?

OBJECTIVE: To assess the incidence of acute pancreatitis in human immunodeficiency virus-positive patients with triglyceride (TG) greater than 500 mg/dL after highly active antiretroviral therapy. METHODS: Sequential TG levels during follow-up and episodes of acute pancreatitis were retrospectively reviewed in 347, 417, and 571 patients enrolled in periods 1 (2000-2002), 2 (2003-2005), and 3 (2006-2008), respectively. The incidence of acute pancreatitis, defined as consistent clinical symptoms and elevated amylase and/or lipase levels, was estimated. RESULTS: A total of 5356 TG measurements were performed during the follow-up for 698.22, 884.14, and 1215.69 person-years in periods 1, 2, and 3, respectively. Overall, 9.89% of patients had at least one TG greater than 500 mg/dL. Five patients with TG less than 500 mg/dL developed acute pancreatitis. The crude incidences of acute pancreatitis were 0.6%, 0.5%, and 0.2%, and the incidence rates were 2.86, 2.26, and 0.82/1000 person-years in periods 1, 2 and 3, respectively (all, P > 0.05). The incidence rates of acute pancreatitis when TG levels were less than 500, less than 1000, and less than 1500 mg/dL ranged from 1.2 to 4.9/1000 person-years, whereas it was 0/1000 person-years when TG levels were greater than 500, greater than 1000, and greater than 1500 mg/dL, respectively. CONCLUSION: The risk of acute pancreatitis was low among human immunodeficiency virus-positive patients who developed hypertriglyceridemia after receiving highly active antiretroviral therapy.

Artificial-epitope mapping for CK-MB assay.

A quantitative method using artificial antibody to detect creatine kinases was developed. Linear epitope sequences were selected based on an artificial-epitope mapping strategy. Nine different MIPs corresponding to the selected peptides were then fabricated on QCM chips. The subtle conformational changes were also recognized by these chips.

Amebiasis among persons who sought voluntary counseling and testing for human immunodeficiency virus infection: a case-control study.

This case-control study aimed to characterize the factors associated with amebiasis, defined as presence of anti-Entamoeba histolytica antibody titers of ≧ 128 by indirect hemagglutination assay, among persons seeking voluntary counseling and testing (VCT) for human immunodeficiency virus (HIV) infection. Between April 2006 and September 2009, 57 of 4,802 persons (1.2%) seeking VCT services were seropositive for E. histolytica infection. Compared with 228 seronegative controls, case subjects were older (odds ratio [OR] for per 1-year increase, 1.098; 95% confidence interval [CI], 1.036, 1.165), less likely to hold bachelor degree or higher (OR, 0.359; 95% CI, 0.152, 0.846), and were more likely to be men who have sex with men (MSM) (OR, 8.382; 95% CI, 2.050, 34.266) and have oral-anal sex (OR, 4.016; 95% CI, 1.711, 9.427) in multiple logistic regression analysis. The MSM, fecal-oral contamination, lower educational achievement, and older age were associated with increased risk for amebiasis among persons seeking VCT for HIV infection.