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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.

Background With initiation of antiretroviral therapy (ART) containing nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) with anti–hepatitis B virus (HBV) activity, the evolution of HBV serologic markers among people living with human immunodeficiency virus (PLWH) who were born in the era of nationwide neonatal HBV vaccination is rarely investigated. Methods This retrospective cohort study evaluated the changes of HBV serologic markers (hepatitis B surface antigen [HBsAg], antibody to hepatitis B surface antigen [anti-HBs], and antibody to hepatitis B core antigen [anti-HBc]) of PLWH who had undergone neonatal HBV vaccination. Clinical characteristics were analyzed and the incidences of evolution of HBV serologic markers were estimated. Results Between 2004 and 2020, 608 PLWH (mean age, 24 years) were included and 62.0% initiated tenofovir-containing ART: 13 (2.1%) were HBsAg-positive, 312 (51.3%) tested triple-negative, 209 (34.4%) had vaccine-induced seroprotection against HBV, and 74 (12.2%) tested positive for anti-HBc with or without anti-HBs. Among 492 PLWH who received a median follow-up of 2.8 years, 4 cases of incident HBV infection occurred (0.59 per 100 person-years of follow-up [PYFU]) in PLWH testing triple-negative at baseline despite ART containing NRTIs with anti-HBV activity. Of PLWH with seroprotection against HBV at baseline, 38 subsequently lost anti-HBs (4.46 per 100 PYFU) and 4 cases of incident HBV infection occurred (0.47 per 100 PYFU). PLWH with an anti-HBs antibody titer ≥100 mIU/mL at baseline (adjusted hazard ratio [aHR], 0.10 [95% confidence interval {CI}: .02–.42]) and CD4 ≥500 cells/µL during follow-up (aHR, 0.51 [95% CI: .30–1.00]) were less likely to lose HBV seroprotection. Conclusions Among young PLWH who had undergone neonatal HBV vaccination, evolution of HBV serologic markers and incident infections occurred despite ART containing NRTIs with anti-HBV activity.

Background Hospital-acquired pneumonia (HAP) are one of the major healthcare-associated infection but its burden and financial impact are lesser studied comparing to ventilator-associated pneumonia (VAP). The study aims to investigate the disease burden, etiology and the outcome among HAP/VAP patients in Taiwan. Methods This is a retrospective study conducted in a teaching hospital in Taiwan. We enrolled patients with HAP/VAP during 1st Jan. 2018 to 31st Dec. 2018. The definition of HAP/VAP was based on definition proposed by the Taiwan Centers of Disease Control and the hospital-wide data was audited prospectively by Center for Infection Control of the hospital. Patients with HAP were further categorized as non-ventilated HAP (nvHAP) and ventilated HAP (vHAP). The burden of HAP/VAP was estimated and the clinical outcomes were compared between nvHAP and vHAP. Results In total, 152 episodes of HAP and 8 episodes of VAP were identified. The incidence of HAP was 0.22 (95% confidence interval [CI], 0.19–0.26) per 1,000 patients-days while that of VAP was 0.27 (95% CI, 0.12–0.53) per 1,000 ventilator-days. The mortality was similar between vHAP and nvHAP in our cohort (55.6% vs. 62.6%, respectively, p = 0.58). However, vHAP was associated with higher length of hospital stay (56 vs. 37 days, p

Objectives The impact of very low-level viremia (VLLV) and low-level viremia (LLV) are rarely investigated among people living with HIV (PLWH) receiving dolutegravir- vs protease inhibitor (PI)-based antiretroviral therapy (ART). Methods Virally suppressed PLWH receiving long-term PI-containing ART were included in this study. The incidences of developing VLLV (plasma HIV RNA load (PVL) 20–49 copies/ml), LLV (PVL 50–999 copies/ml), and virological failure (any PVL ≥ 1000 copies/ml) were compared between those switched to dolutegravir-based ART and those remaining on PI-containing ART. Results A total of 183 PLWH were switched to dolutegravir-based regimens and 309 remained on PI-containing regimens. The incidences of VLLV and LLV were 26.5 and 13.2 per 100 person-years of follow-up in the dolutegravir group, respectively, and 17.1 and 7.0 per 100 person-years of follow-up in the PI group; there were no statistically significant differences after adjusting for confounders. The rate of virological failure was 1.3 per 100 person-years of follow-up in the dolutegravir group and 1.9 per 100 person-years of follow-up in the PI group (p = 0.32). Neither VLLV nor LLV was related to subsequent virological failure. Conclusions Among virally suppressed PLWH, the risk of developing VLLV or LLV were similar between those switched to dolutegravir-based therapy and those who continued PI-based therapy. VLLV and LLV were not associated with subsequent virological failure.

Background The optimal loading dose of teicoplanin in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) has never been determined by therapeutic drug monitoring. This study investigated the appropriateness of proposed loading dose regimens of teicoplanin when administered to patients receiving VA-ECMO by using a previously proposed loading dosage and measuring the teicoplanin trough concentration (Ctrough). Methods Patients who initiated teicoplanin therapy while receiving VA-ECMO were enrolled. Every included patient received four loading doses of teicoplanin at a dose of 12 mg/kg. The first three doses were administered 12 h apart, and the fourth dose was administered 24 h after the third dose. Blood samples were collected before administering the maintenance dose (i.e., the fifth dose), and the teicoplanin Ctrough was measured. Serum teicoplanin levels were determined using an Agilent 1290 ultra-high performance liquid chromatography system. Results The teicoplanin Ctrough was successfully tested in 11 patients. Their median age was 68.2 years, and 81.8% of them were men. The median of each loading dose was 11.6 (range, 10.7–12.8) mg/kg. The median teicoplanin Ctrough was 22.01 (range, 14.85–44.84) mg/L. All patients had a Ctrough of more than 10 mg/L, whereas 90.9% (10/11) of the patients achieved a Ctrough of more than 15 mg/L. Conclusion The loading dosage consisting of four doses of teicoplanin administered within the first 72 h at a dose of 12 mg/kg/dose could achieve an adequate therapeutic Ctrough of teicoplanin in patients receiving VA-ECMO.

Real-world experience with low-level viraemia (LLV) and its impact remain less reported among people living with HIV (PLWH) who receive antiretroviral therapy (ART) containing second-generation integrase strand transferase inhibitors, including dolutegravir and bictegravir. This retrospective cohort study included virally suppressed PLWH who achieved plasma HIV-RNA viral load (PVL)50 copies/mL for ≥6 months and were switched to either dolutegravir- or bictegravir-based ART. Incidence rates of developing LLV events (PVL, 50-200 copies/mL) and virologic failure (VF) (PVL ≥1000 copies/mL) were compared between the dolutegravir and bictegravir cohorts. A total of 623 and 862 PLWH switched to dolutegravir-based and bictegravir-based ART, respectively, were included. The incidence rate of developing LLV was 6.2 per 100 person-years of follow-up (PYFU) in the bictegravir cohort and 3.8 per 100 PYFU in the dolutegravir cohort [incidence rate ratio (IRR) = 1.63, 95% confidence interval (CI), 0.90-2.95; P = 0.08], while rates of VF were 0.69 per 100 PYFU and 0.95 per 100 PYFU, respectively, in the bictegravir and dolutegravir cohorts (IRR = 0.72, 95% CI 0.12-3.39; P = 0.34). Presence of LLV events was not associated with subsequent VF in multivariate analysis. Secondary analysis also demonstrated that resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (NRTIs) before switch were not associated with adverse virologic outcomes in either cohort. In conclusion, among virally suppressed PLWH, the incidences of developing LLV or VF were similar after switch to dolutegravir- or bictegravir-based ART. Pre-existing RAMs to NRTIs or LLV events were not associated with subsequent VF.

Background/purpose: Acute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan. Methods: Between 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry. Results: The proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log10 copies/ml, and median CD4 count was 307 cells/mm3. A total of 68 patients (27%) had baseline CD4 count less than 200 cells/mm3. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p = 0.013) and aspartate aminotransaminase levels (OR, 3.49; p = 0.002) were associated with high PVL (>5 log10 copies/ml); and high baseline PVL (OR, 2.64; p = 0.002) was associated with symptomatic acute HIV infection. Conclusions: Manifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200 cells/mm3 or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression. Keywords: Acute HIV infection, Aseptic meningitis, Combination antiretroviral therapy, Fiebig stage, Infectious mononucleosis

Background: Complicated urinary tract infection (cUTI) is often associated with drug-resistant pathogens and requires therapy with broad-spectrum antibiotics. Choice of empiric therapy should be based on an evaluation of clinical efficacy and medical costs. We used a cost-utility model to compare the empiric use of a new antibiotic, ceftolozane/tazobactam with piperacillin/tazobactam in patients with cUTI. Methods: The analysis was conducted using a decision tree and patient-level simulation approach. Patients in the model received empiric antibiotic treatment with ceftolozane/tazobactam or piperacillin/tazobactam. Outcomes included mortality, medical costs and quality-adjusted life years (QALYs). Parameters related to pathogen distribution, length of hospital stay and medical costs, were estimated based on a cohort of patients with cUTI admitted during July 1st, 2015 to August 31st, 2016 to the National Taiwan University Hospital, a teaching hospital in Taiwan. Isolates used for the patient-level simulation to determine susceptibility to either drug were taken from the Study for Monitoring Antimicrobial Resistance Trend database. Results: The analysis was performed on a simulation of 1000 patients. Empiric use of ceftolozane/tazobactam leads to higher total medical costs (USD 4199.01 per patient versus USD 3594.76, respectively) but also more discounted QALYs (4.80 versus 4.78, respectively). The additional cost per discounted QALY gained associated with empiric ceftolozane/tazobactam was 32,521.08 USD (956,282 NTD). Conclusions: Our results suggest that empiric use of ceftolozane/tazobactam for the treatment of cUTI could be a cost-effective choice in Taiwan. Keywords: Complicated urinary tract infection, Ceftolozane/tazobactam, Piperacillin/tazobactam, Cost-effectiveness analysis, Cost-utility analysis

Prolonged exposure to regimens containing protease inhibitors (PIs) as second-line therapy for human immunodeficiency virus (HIV) infection may have a negative impact on metabolic profiles and increase the risk of cardiovascular diseases. Real-world experience with dolutegravir (DTG)-based regimens as alternatives to PI-based regimens is limited in antiretroviral-experienced patients with previous failure or intolerance to first-line therapy. The current study included HIV-positive patients receiving PI-containing regimens with viral suppression for ≥6 months. Virological response and lipid profiles were compared between patients who were subsequently switched to DTG-based therapy plus nucleoside reverse transcriptase inhibitors (NRTIs) and those remaining on their PI-containing regimen at Week 48. In total, 189 patients were switched to DTG-based regimens and 313 remained on PI-containing regimens during the observation period. Patients in the DTG group were younger (mean age 40.0 years vs. 44.6 years) and were more likely to have a previous history of virological failure (44.4% vs. 19.5%) than those in the PI group. At Week 48, 1.1% of the DTG group and 3.8% of the PI group had virological non-response (HIV-RNA load >50 copies/mL) (difference, –2.7%, 95% CI –5.5% to 0.5%). The presence of M184V/I mutation and other NRTI resistance-associated mutations (RAMs) did not increase the risk of virological failure in either group. Patients switched to DTG-based therapy had statistically significant improvement of lipid profiles. Among virally suppressed HIV-positive patients, a switch to DTG-based therapy was non-inferior to continuation of PI-based therapy in virological effectiveness at Week 48, even in the presence of NRTI RAMs.

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)‐positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV‐positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV‐positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case‐control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow‐up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow‐up of 611 days. In a case‐control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292‐2.323, per 10‐kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067‐7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020‐0.154) and 0.837 (95% CI, 0.704‐0.979, per 100‐cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two‐dose HAV vaccination occurred in 3.9% of HIV‐positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV‐positive adults with predictors of early seroreversion.

Objectives Real-world experience regarding the effectiveness of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/C/FTC/TAF) as a switch regimen is sparse among people living with HIV (PLWH) harbouring the M184V/I mutation with or without thymidine analogue-associated mutations (TAMs). Methods In this retrospective multicentre study, PLWH who were switched to EVG/C/FTC/TAF after having achieved viral suppression (plasma HIV RNA Results Overall, 100 case patients with the M184V/I mutation were identified, including 6 (6.0%) with K65R and 13 (13.0%) with at least one TAM, and were matched to 400 controls in terms of gender, age (mean = 40.3 versus 39.7 years) and cumulative exposure duration to tenofovir disoproxil fumarate (median = 146 versus 143 weeks). At Week 48, the rate of virological non-success for the case patients and controls was 5.0% (5/100) and 3.3% (13/400), respectively (difference = 1.7%; 95% CI = −2.9%–6.3%), while the rate of virological success was 88.0% and 89.5% for the case patients and controls, respectively. The presence of the K65R mutation or TAMs was not associated with virological non-response. Conclusions Among virally suppressed PLWH, EVG/C/FTC/TAF is effective in maintaining viral suppression at Week 48 despite archived M184V/I mutation with or without TAMs.

Outbreaks of hepatitis A virus (HAV) infection have been occurring among men who have sex with men in the Asia-Pacific region, the United States, and several European countries since June 2015 and recently among persons who are homeless and use illicit drugs in the United States. We evaluated the serologic responses and effectiveness of HAV vaccination in human immunodeficiency virus (HIV)-positive individuals during the outbreak in Taiwan. From June 1, 2015, to September 30, 2016, anti-HAV immunoglobulin G was prospectively determined among all HIV-positive individuals. We prospectively observed 1,533 HAV-seronegative, HIV-positive individuals (94.1% being men who have sex with men with a median cluster of differentiation 4 (CD4) count of 550 cells/μL) who were advised to receive two doses of HAV vaccine administered 6 months apart. Of them, 1,001 individuals (65.3%) received at least one dose of HAV vaccine during the study period and 532 (34.7%) declined to receive vaccine. The primary endpoints were serologic response at weeks 28-36 and acquisition of HAV infection during follow-up. The incidence rate of acute HAV infection was 3.7 and 99.3 per 1,000 person-years of follow-up in the vaccinated and unvaccinated groups, respectively, resulting in a vaccine effectiveness of 96.3%. At weeks 28-36, the seroconversion rates were 63.8% and 93.7% in the intention-to-treat and per-protocol analyses, respectively. The factors associated with seroconversion at weeks 28-36 were younger age (per 1-year decrease, adjusted odds ratio, 1.08; 95% confidence interval, 1.02-1.12) and undetectable plasma HIV RNA load (adjusted odds ratio, 3.19; 95% confidence interval, 1.32-7.68). Conclusion During the outbreak of acute hepatitis A, two-dose HAV vaccination is effective at preventing HAV infection among HIV-positive individuals receiving combination antiretroviral therapy; our data highlight the importance of HAV serologic screening and vaccination to prevent outbreaks of acute hepatitis A in at-risk populations. (Hepatology 2018;68:22-31).

We evaluated the serologic responses to different 2-dose combinations of the inactivated hepatitis A virus (HAV) vaccines Havrix and Vaqta among human immunodeficiency virus-positive individuals during an acute hepatitis A outbreak in Taiwan. In this 16-month retrospective study, one group received 1 dose of Havrix followed by 1 dose of Vaqta, and another group received 2 doses of Vaqta. The Havrix-Vaqta and Vaqta-Vaqta groups achieved similar seroconversion rates at weeks 28-36 (82.3% and 80.9%, respectively; absolute difference, 1.3% [95% confidence interval {CI}, -6.3%-3.7%]) and week 48 (94.7% and 94.4%, respectively; absolute difference, 0.3% [95% CI, -2.6%-3.2%]), suggesting the interchangeability of different combinations of HAV vaccines. The significantly higher seroconversion rate after the first dose of Vaqta, compared with the dose of Havrix (53.0% vs 32.4%) may provide potential benefits in preventing HAV infection during the outbreak.

Background Serological responses to revaccination against hepatitis B virus (HBV) are unclear in HIV-positive adults who had undergone neonatal HBV vaccination and whose antibodies against HBV had waned in the era of combination antiretroviral therapy (cART). Methods Between 2000 and 2017, 666 HIV-positive men who have sex with men (MSM) who were born after 1986, when nationwide neonatal HBV vaccination programme was implemented in Taiwan, were included for analyses. A serological response was defined when a hepatitis B surface antibody (anti-HBs) titre ≥10 mIU/mL was measured 4-24 weeks after the third dose of HBV vaccination. Results During the study period, 295 (48.7%) HIV-positive MSM (mean age, 23.2 years) who had lost HBV seroprotection were eligible for revaccination; 171 (58.0%) received at least 1 dose (20-μg) of HBV vaccine and 116 (39.3%) completed the 3-dose schedule. The serological response rate to 3 doses of HBV revaccination was 74.0% and the rate of high-titre response (anti-HBs titre ≥100 mIU/mL) was 46.0%. The CD4 count before the first dose (per 50-cell/μL increment, adjusted odds ratio, 1.14; 95% confidence interval, 1.01-1.29) was positively associated with the serological response. The incident rate of HBV infection was 9.2 per 1000 person-years of follow-up among the patients who were non-responders after revaccination. Conclusions Despite HBV vaccination in the neonatal period, the serological response rate to HBV revaccination in HIV-positive MSM was modest and could wane rapidly. Regular testing of anti-HBs should be integrated into the HIV care despite cART containing HBV-active agents.

BACKGROUND Among HIV-positive individuals, seroprotection for hepatitis A virus (HAV) following primary vaccination may wane with time. However, seroresponses to HAV revaccination are rarely investigated among HIV-positive patients who have lost protective antibodies after primary vaccination. METHODS During the outbreak of acute hepatitis A in Taiwan after June 2015, HAV-seronegative, HIV-positive individuals were advised to receive two doses of HAV vaccines at 24 weeks apart. A retrospective 1:2 matched case-control study was conducted to compare the seroresponses at weeks 4, 24, 28 and 48 of HAV vaccination between those who underwent revaccination after having lost protective antibodies (case patients) and those who underwent primary vaccination (controls). RESULTS Seventy-five case patients and 150 matched controls were included. The serological response rates were consistently higher among the case patients than controls: 88.1% vs 10.5% at week 4 following the first dose of HAV vaccination (P

Objectives Aortic root abscess (ARA) is a catastrophic complication of aortic root endocarditis, involving both native and prosthetic valves, which often warrants surgical intervention. Currently, aortic valve replacement (AVR) and aortic root replacement (ARR) are the most widely employed techniques. However, evidence that directly compares these methods is scarce. In this meta-analysis, we aimed to describe the surgical outcome of ARA when using different surgical methods. Methods In this meta-analysis, we performed literature searches in the EMBASE and PubMed databases and reviewed articles describing postoperative results of ARA that were published before 30 June 2016. After extracting the published data, we used a random-effects model to perform meta-analysis and compare the postoperative outcomes of ARA after management with AVR or ARR. Results Seven published studies were included in this meta-analysis, which includes 781 episodes of infective endocarditis complicated with ARA. There was no significant difference in the 30-day postoperative mortality rate among patients receiving ARR [23.8%, 95% confidence interval (CI) 17.8-30.6] compared with AVR (19.1%, 95% CI 13.3-26.1%), with a relative risk ratio of 1.30 (95% CI 0.84-2.00). However, patients receiving ARR were associated with statistically significant lower rates of reoperation within 1 year (relative risk 0.50, 95% CI 0.26-0.94). Conclusions In our meta-analysis, ARR was associated with a 50% risk reduction of reoperation within 1 year among patients with ARA. There was no significant difference in the 30-day postoperative mortality rate between patients receiving ARR and patients receiving AVR; comparison of the long-term outcomes after these 2 procedures warrants further investigation.

Background An unprecedented outbreak of acute hepatitis A has occurred among MSM in Taiwan since June 2015. We aimed to describe the seroepidemiology of HAV infection and to investigate the relationship between HAV vaccination and the incidence of acute hepatitis A among HIV-positive patients at the largest designated hospital for HIV care during the outbreak. Methods Between 2012 and 2016, the HAV serostatus, vaccination history, and clinical characteristics of HIV-positive patients were retrospectively reviewed. A case-control study was performed to identify the factors associated with acute hepatitis A. The trends of HAV vaccination rate and incidence of acute hepatitis A among HAV-seronegative patients were examined during the outbreak. Results During the 4.5-year period, 2088 HIV-positive patients with a mean age of 37.7 years and 90.2% being MSM were included. The overall HAV seroprevalence was 34.3%, which was significantly higher in older and non-MSM patients. The estimated incidence rate of acute hepatitis A was 52.6 cases per 1000 person-years of follow-up during the outbreak. The associated factors with acquiring acute hepatitis A were recent syphilis and having not received HAV vaccines. The HAV vaccination rate during the outbreak increased from 4.7% to 70.6% and the incidence rate of acute hepatitis A declined when up to 65% of the patients were immunized or tested positive for HAV. Conclusions The seroprevalence of HAV infection was low in the younger HIV-positive individuals. Prevention of acute hepatitis A was achieved among HIV-positive, HAV-seronegative patients through HAV vaccination and increased herd immunity during the ongoing outbreak. This article is protected by copyright. All rights reserved.

Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.

ObjectivesRapid initiation of antiretroviral therapy (ART) engenders faster viral suppression but with suboptimal rates of durable viral suppression and engagement in care, as reported by clinical trials in resource-limited settings. Real-world experience with rapid ART initiation remains limited in resource-rich settings.DesignRetrospective cohort study.SettingA tertiary hospital in metropolitan Taipei, Taiwan.ParticipantsWe included 631 patients newly diagnosed as having HIV infection between March 2014 and July 2018.Main outcome measuresRapid ART initiation was defined as starting ART within 7 days after HIV diagnosis confirmation. HIV diagnosis, ART initiation and viral suppression dates and clinical outcome data were collected by reviewing medical records. The rates of loss to follow-up (LTFU), engagement in care and virological rebound at 12 months were compared between patients with rapid ART initiation and those with standard initiation.ResultsRapid ART initiation increased from 33.8% in 2014 to 68.3% in 2017, and the median interval between HIV diagnosis and viral suppression (HIV RNA load ConclusionsRapid ART initiation was associated with a higher rate of engagement in care at 12 months and shortened interval from diagnosis to HIV suppression. Delayed ART initiation may increase onwards HIV transmission considering the high rates of STIs.Ethics approvalThe study was approved by the Research Ethics Committee of National Taiwan University Hospital (Registration No. 201003112R).

Background/purpose Early initiation of antiretroviral therapy (ART) reduces the risks for serious infections and mortality. We aimed to assess the outcomes of initiating ART among HIV-positive Taiwanese according to the CD4 cut-off values by the WHO recommendations. Methods We reviewed medical records of patients with newly diagnosed HIV infection between 2004 and 2015 and 3 groups of patients were defined according to the timing of ART initiation based on CD4 count recommended by WHO: Group 1 between 2004 and 2009; Group 2 between 2010 and 2012; and Group 3 between 2013 and 2015. The primary outcome was all-cause mortality. All patients were followed until 2 years after the last patient was included in each group. Results Of 2022 patients included, the mortality rate was 18.28, 14.01, and 9.10 deaths per 1000 person-years of follow-up (PYFU) in Groups 1, 2, and 3, respectively. In multivariable Cox regression analysis, factors associated with mortality were age (per 1-year increase, adjusted hazard ratio [AHR], 1.06; 95% CI, 1.05–1.08), presence of AIDS-defining disease at HIV diagnosis (AHR, 4.81; 95% CI, 2.99–7.74), solid-organ malignancy (AHR, 3.10; 95% CI, 1.86–5.18), and initiation of ART (AHR, 0.09; 95% CI, 0.05–0.16). By competing risk regression model for non-AIDS-related death, the AHR for Group 3 versus Group 1 was 0.27 (95% CI, 0.09–0.80). Conclusions While continued efforts are needed to improve early diagnosis and linkage to care, initiation of cART improved survival among HIV-positive patients in Taiwan according to the increasing CD4 cut-off values that were recommended by the WHO.

Background Tenofovir disoproxil fumarate (TDF) is active against both HBV and HIV. Whether the introduction of TDF-containing combination antiretroviral therapy (cART) has improved the outcome of HIV/HBV-coinfected patients remains unclear in areas of higher HBV endemicity. Methods We retrospectively reviewed medical records of newly diagnosed antiretroviral-naive HIV-infected patients between 2007 and 2015. Four groups of patients were defined, according to the HBV status and availability of TDF for HIV treatment in Taiwan in 2011. The primary outcome was all-cause mortality. Results During the 9-year study period, 1,723 HIV-infected patients were included, with a median age of 31 years and baseline CD4 count of 273 cells per μL. The HBV seroprevalence had declined from 18.1% (125/692) in the pre-TDF era to 10.1% (104/1031) in the post-TDF era. The respective mortality rate for HIV/HBV-coinfected and HIV-monoinfected patients in the pre-TDF era was 23.2 (95% CI, 12.5-43.1) and 9.6 (95% CI, 6.1-15.0) deaths per 1000 person-years of follow-up [PYFU], and the respective mortality rate in the post-TDF era was 15.7 (95% CI, 7.0-34.8) and 8.0 (95% CI, 5.5-11.6) deaths per 1000 PYFU. The adjusted hazard ratio for mortality in multivariate Cox proportional-hazards regression analysis among HIV/HBV-coinfected patients compared to HIV-monoinfected patients was 2.79 (95% CI, 1.25-6.22) in pre-TDF era and 1.11 (95% CI, 0.45-2.72) in post-TDF era. Conclusions In this country of high HBV endemicity, the adverse impact of chronic HBV infection on the survival observed in the pre-TDF era has significantly diminished among HIV/HBV-coinfected patients compared to HIV-monoinfected patients in the era of TDF-containing cART.

Background This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak. Methods Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017. Results A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load

In order to investigate the effect of bio-coal on the carbothermic reduction of laterite ores, carbothermic reduction experiments of two type laterite ores mixed with bio-coal were conducted in this research. The reduction experiments were carried out at 1173­1673K for 1800s in Ar. Compared reduction results of coal and bio-coal show increasing the nickel content with increasing temperature. Bio-coal had become the reductant, the nickel content of limonite specimens and saprolite specimens had been raised from 1.18mass% (before reduction) to 1.64mass% (after reduction at 1373K for 1800s) and from 3.43mass% (before reduction) to 4.93mass% (after reduction at 1473K for 1800s), respectively. The major phases of limonite specimens were Fe1.833(OH)0.5O2.5 and Fe2SiO2. After the reduction at 1473K for 1800s, the major phase was metal Fe. The major phases of the saprolite specimens were Fe(CO3), Fe3O4 ,F e2SiO4 and Al3S4. After the reduction at 1473K for 1800s, the major phases were Fe, Fe0.64Ni0.36 and i-Fe10.8Ni. The morphological observation of limonite and saprolite specimens shows that the pelletshaped specimen became a dense area and the core of the pellet had loose structure at 1173­1374K for 1800s. The core of pellet was produced small spherical metal phase at 1473K for 1800s, this temperature was the soft melting temperature. Finally, the pellet produced nickel-iron alloy phase and iron was separated from the oxide phase at 1673°C for 1800s. [doi:10.2320/matertrans.M2014315]

Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.

We aimed to compare the risks of creatine kinase (CK) elevation between patients receiving dolutegravir-based antiretroviral therapy (ART) and those receiving non-integrase strand transfer inhibitor (InSTI)-based ART. HIV-positive patients seeking HIV outpatient care between February 2017 and March 2018 were retrospectively reviewed to collect information on ART, practices of vigorous exercise, and laboratory tests including CK level, plasma HIV RNA load, and concurrent medications. The incidences of CK elevation were estimated among patients receiving dolutegravir-based ART and those receiving non-InSTI-based ART. During the 14-month study period, 1406 patients (mean age 39.4 years and 96.9% being male) were included. The incidence rate of grade 3 or grade 4 CK elevation (>10-fold of the upper limit of normal) was 2.0 per 100 person-years of follow-up (PYFU) and 1.3 per 100 PYFU in the dolutegravir and non-InSTI group, respectively (P = .32). While dolutegravir group had a higher rate of CK elevation of any level than non-InSTI group (22.9 vs 17.4 per 100 PYFU, P = .01), the risk was associated with weight (adjusted odds ratio [aOR], per 10-kg increase, 1.03; 95% CI, 1.02–1.04), duration of exercise (aOR, per 1-hour increase, 1.02; 95% CI 1.01–1.03), but not with dolutegravir-based ART (aOR, 1.00; 95% CI, 0.99–1.06) after adjusting for the testing frequency of serum CK in the multivariate generalized estimating equation model. No patients were hospitalized or switched ART due to CK elevation. Serum CK elevation was associated with weight and duration of exercise among HIV-positive patients receiving ART, but not with dolutegravir-based ART.

In the integrated steel mills fabrication processes, the by-product of flue dust and electrostatic precipitator dust were found to be rich with large amounts of iron and carbon content and it could be recycled as a raw material for blast furnaces. In this study, we use the “Cold-bonded Pellet; CBP” technique to prepare the recycling samples for subsequent processing. Therefore, this study investigated under a fixed amount of bentonite added, the choice of different types of bentonite on the powder granulation performance and strength of particle duration effects, bentonite used as a basis for adjustment. The results showed that Bentonite samples of the granulation efficiency increase, relative to its yield and the rate of sticky increase. In general, CBP particle compressive strength increased, duration have increased, and found that curing condition B are large than the A method. In addition, by particle size analysis results show that, bentonite average particle size of 11-12μm have better compressive strength. Comprehensive assessment of granulation and mechanical properties, of which A label in four Bentonite can be preferred.