Combined bictegravir, emtricitabine and tenofovir alafenamide for treating people with HIV: a plain language summary of the BICSTaR study up to 1 year.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article about an ongoing study called the BICSTaR study.The BICSTaR study includes people with HIV (human immunodeficiency virus) who are taking a medicine called bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single tablet that contains 3 different drugs for the treatment of HIV. The drugs work together to reduce the levels of HIV so that the virus can no longer be detected by a blood test.People taking part in the study are adults with HIV living in Europe, Canada, Israel, Japan, South Korea, Singapore and Taiwan. People take 1 tablet of B/F/TAF once a day. They are either taking B/F/TAF as their first treatment for HIV, or they have switched to B/F/TAF from another HIV treatment.Researchers looked at how well B/F/TAF worked and how safe it was in people who took B/F/TAF for a year. WHAT ARE THE KEY TAKEAWAYS?: Researchers found that B/F/TAF worked well in almost all people in the study by reducing levels of HIV in the blood. The virus could not be found in the blood of more than 9 out of 10 (94%) people who were taking B/F/TAF as their first HIV medicine and more than 9 out of 10 people (97%) who had taken another HIV medicine before starting B/F/TAF. This is known as having an 'undetectable viral load' and is a major goal for HIV treatment success. Researchers did not find any evidence of HIV developing resistance to B/F/TAF, which might stop B/F/TAF from working properly.Around 1 out of 10 people (13%) had side effects (any unwanted sign or symptom that people have when taking a medicine that researchers think might be caused by the medicine) that might have been caused by B/F/TAF. Most of these side effects were not classified as serious. Less than 1 out of 100 (0.1%) people had serious side effects that might have been caused by B/F/TAF. Only 6 out of 100 people stopped taking B/F/TAF due to side effects caused by B/F/TAF. As a result, more than 9 out of 10 people (95%) took B/F/TAF for at least 1 year. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: B/F/TAF worked well in people with HIV in this study. Most people (around 9 out of 10) did not have any side effects.

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018-2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and ß-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC ß-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel ß-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. CONCLUSIONS: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

In vitro susceptibilities of Stenotrophomonas maltophilia isolates to antimicrobial agents commonly used for related infections: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2004-2020.

Stenotrophomonas maltophilia is an emerging opportunistic pathogen for which there are limited therapeutic options because of intrinsic multidrug resistance. S. maltophilia isolates were collected as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program and minimum inhibitory concentrations (MICs) were determined using broth microdilution methods. Susceptibility was interpreted according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Isolates with tigecycline MIC ≤2 mg/L were defined as susceptible, using the United States Food and Drug Administration criteria of Enterobacterales. A total of 2330 S. maltophilia isolates were collected from 47 countries worldwide in the ATLAS program from 2004 to 2020. Most patients were hospitalized (92.3%, 2151/2330) and respiratory tract infections (47.8%, 1114/2330) were the most common source of isolates. Minocycline had the highest susceptibility rate (98.8%), followed by levofloxacin (85.0%), trimethoprim-sulfamethoxazole (TMP-SMX) (84.4%), and ceftazidime (53.7%). A total of 98.3% (2290/2330) of S. maltophilia isolates had tigecycline MIC ≤2 mg/L. Among the S. maltophilia isolates exhibiting resistance to levofloxacin and ceftazidime, 89.3% (150/168) and 97.3% (692/711), respectively, were susceptible to tigecycline. Eight countries provided more than 30 isolates and were selected for comparison. Geographical difference in antimicrobial resistance was significant for levofloxacin, minocycline, and tigecycline (all P<0.05) but not for ceftazidime (P=0.467). These in vitro data demonstrated that minocycline had a higher susceptibility rate than levofloxacin and ceftazidime, and that tigecycline could be an alternative or salvage option for the treatment of S. maltophilia infections.

A new collaborative care approach toward hepatitis C elimination in marginalized populations.

BACKGROUND: Treating marginalized populations with HCV infection for elimination is faced with the challenge for the integration of HCV screening service offered for patients often moving across multiple settings. We envisaged a novel collaborative care approach to identify to what extent HCV patients overlapped between and within these multiple institutions and reported the findings of treatment coverage of these marginalized populations after HCV care cascades. METHODS: We enrolled 7765 patients residing in the Changhua County, Taiwan offered with HCV screening from correctional institutions, HIV clinics, methadone clinics, and the existing HIV surveillance program (four subgroups including police-arrested people, probationers, non-injection drug user, and high-risk behavior people) between 2019 and 2020. The collaborative care and information were integrated through a teamwork of gastroenterologists, psychologists, infectious disease specialists, and nursing coordinators under the auspices of local health authority. RESULTS: The overall participation rate in HCV screening was 92.65% (7194/7765). The prevalence rate was the highest in methadone clinics (90.17%) followed by correctional institutions (37.67%), HIV clinics (34.60%), and the surveillance program (18.14%). We found 25.41% (77/303) of methadone clinic patients, 17.65% (129/731) of HIV clinic patients, and various proportions for 44.09% (41/93) of deferred prosecuted or probationers under surveillance program were also recruited into other settings. Individuals' patient flow within setting was more frequent than that between setting. After calibrating the overlap of patient flow, a total of 1700 anti-HCV positives out of 4074 after screening were traced with available follow-up information to complete 92.52% treatment coverage of 1177 RNA-positives (77.23%) diagnosed from 1524 undergoing RNA testing with similar findings across multiple settings. CONCLUSION: A new collaborative integrated care was adopted for elucidating patient flow between and within multiple settings in order to calibrate the accurate demand for HCV care cascades and enhance HCV treatment coverage in marginalized populations.

Week 96 Results of Switching from Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide among HIV/Hepatitis B Virus-Coinfected Patients.

Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g, P < 0.001) and ß2-microglobulin-to-creatinine ratio (165 versus 83 µg/g, P < 0.001) continued to decrease at week 96. BMD of the spine and hip slightly increased (mean change, +0.9% and +0.5%, respectively). The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 (116 versus 141, 166 versus 190, 99 versus 117, and 42 versus 47 mg/dL, respectively; all P < 0.001), and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch. IMPORTANCE Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection.

Switching to coformulated bictegravir, emtricitabine, and tenofovir alafenamide maintained viral suppression in adults with historical virological failures and K65N/R mutation.

OBJECTIVES: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. METHODS: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. RESULTS: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. CONCLUSION: Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression.

Seroprevalence of varicella-zoster virus antibody and immunogenicity of live attenuated varicella vaccine in healthcare workers in Taiwan.

BACKGROUND: Healthcare workers (HCWs) without evidence of immunity to varicella-zoster virus (VZV) are recommended to undergo varicella vaccination. Immunogenicity of live attenuated varicella vaccine has rarely been investigated among HCWs in Taiwan. METHODS: Anti-VZV immunoglobulin G (IgG) titer was checked for all HCWs at Changhua Christian Hospital from 2011 to 2017. One-dose and two-dose (separated by 4-8 weeks) vaccines were administered to HCWs with equivocal and negative anti-varicella IgG results, respectively. Follow-up anti-VZV IgG was determined at least 4 weeks after completion of vaccination. Factors associated with seroconversion to varicella vaccination were analyzed. RESULTS: Among 2406 included HCWs, the anti-VZV IgG serostatus was tested positive, equivocal and negative in 1924 (79.9%), 117 (4.9%) and 365 (15.2%), respectively. The seroprevalence had decreased from 88.0% (235/267) in 2011 to 72.2% (270/374) in 2017 (p for trend <0.05). A total of 67.8% (327/482) HCWs completed scheduled vaccination and serological follow-up. The seroconversion rates for HCWs with baseline equivocal and negative anti-VZV IgG results were 100% (80/80) and 79.4% (196/247) after one- and two-dose vaccination, respectively. In multivariate analysis, obesity (adjusted odds ratio, 0.308; 95% confidence interval [CI], 0.11-0.94, p = 0.039) was the only factor statistically significantly associated with seroconversion to vaccination. CONCLUSION: Decreasing trends of seroprevalence of VZV were observed among HCWs from 2011 to 2017. HCWs who were obese were less likely to respond to varicella vaccination.

Care cascade of tuberculosis infection treatment for people living with HIV in the era of antiretroviral therapy scale-up.

Testing and treatment of tuberculosis infection (TBI) are recommended for people living with HIV (PLWH). We aimed to evaluate the care cascade of TBI treatment among PLWH in the era of antiretroviral therapy (ART) scale-up. This retrospective study included adult PLWH undergoing interferon-gamma release assay (IGRA)-based TBI screening during 2019-2021. PLWH testing IGRA-positive were advised to receive directly-observed therapy for TBI after active TB disease was excluded. The care cascade was evaluated to identify barriers to TBI management. Among 7951 PLWH with a median age of 38 years and CD4 count of 616 cells/mm3, 420 (5.3%) tested positive and 38 (0.5%) indeterminate for IGRA. The TBI treatment initiation rate was 73.6% (309/420) and the completion rate was 91.9% (284/309). More than 80% of PLWH concurrently received short-course rifapentine-based regimens and integrase strand transfer inhibitor (InSTI)-containing ART. The main barrier to treatment initiation was physicians' concerns and patients' refusal (85.6%). The factors associated with treatment non-completion were older age, female, anti-HCV positivity, and higher plasma HIV RNA. Our observation of a high TBI completion rate among PLWH is mainly related to the introduction of short-course rifapentine-based regimens in the InSTI era, which can be the strategy to improve TBI treatment uptake.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Changing epidemiology of shigellosis in Taiwan, 2010-2019: an emerging threat to HIV-infected patients and men who have sex with men.

Shigellosis appears to increase in certain at-risk populations in developed countries. Based on the nationwide surveillance, the annual incidence of shigellosis in Taiwan (1999-2019) was 0.38-5.77 cases per 100,000 people. Indigenous shigellosis has mostly affected men who have sex with men (MSM) and people living with HIV (PLWH) since 2015. In this retrospective study, compared with those diagnosed before 2015, indigenous cases diagnosed during 2015-2019 mostly occurred in male adults (96.0% vs 47.1%, P < 0.001), with a longer hospital stay (median 5.0 vs 3.5 days, P = 0.029) and different coinfections. The predominant strains in 2015 and 2016 were ciprofloxacin-resistant Shigella sonnei and azithromycin non-susceptible Shigella flexneri (S. flexneri) 3a, which had been replaced by ciprofloxacin-resistant S. flexneri 2a since 2018. Notably, six indigenous cases were caused by cefotaxime-resistant S. flexneri. Inappropriate use of empiric antibiotic treatment was common. In conclusion, there is an ongoing spread of ciprofloxacin-resistant shigellosis among PLWH and MSM and cefotaxime-resistant S. flexneri is an emerging threat in Taiwan.

Impact of Nutritional Assessment on the Clinical Outcomes of Patients with Non-albicans Candidemia: A Multicenter Study.

Several studies have demonstrated that malnutrition is a negative prognostic factor for clinical outcomes. However, there is limited evidence for the effect of malnutrition on clinical outcomes in patients with candidemia. We investigated the relationship between malnutrition and all-cause 28-day mortality among patients with non-albicans candidemia. Between July 2011 and June 2014, all adult patients with non-albicans candidemia, including C. tropicalis, C. glabrata, C. parapsilosis and so on, were enrolled. The Malnutrition Universal Screening Tool (MUST) scores were used to determine the patients' nutritional status before the onset of candidemia. A total of 378 patients were enrolled; 43.4% developed septic shock and 57.1% had a high risk of malnutrition (MUST ≥ 2). The all-cause 28-day mortality rate was 40.7%. The Cox proportional hazards model revealed that C. tropicalis (HR, 2.01; 95% CI, 1.24-3.26; p = 0.005), Charlson comorbidity index (HR, 1.10; 95% CI, 1.03-1.18; p = 0.007), Foley catheter use (HR, 1.68; 95% CI, 1.21-1.35; p = 0.002), concomitant bacterial infections (HR, 1.55; 95% CI, 1.11-2.17; p = 0.010), low platelet count (HR, 3.81; 95% CI, 2.45-5.91; p < 0.001), not receiving antifungals initially (HR, 4.73; 95% CI, 3.07-7.29; p < 0.001), and MUST ≥ 2 (HR, 1.54; 95% CI, 1.09-2.17; p = 0.014) were independently associated with all-cause 28-day mortality. A simple screening tool for nutritional assessment should be used for patients with non-albicans candidemia to detect early clinical deterioration, and a tailored nutritional care plan should be established for malnourished individuals, to improve their clinical outcomes.

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study.

INTRODUCTION: Screening for cryptococcal antigen (CrAg) is recommended for people living with HIV (PLWH) who present with low CD4 lymphocyte counts. Real-world experience is important to identify gaps between the guidelines and clinical practice. We investigated the trends of CrAg testing and prevalence of cryptococcal antigenemia among PLWH at the time of HIV diagnosis and the related mortality in Taiwan from 2009 to 2018. METHODS: Medical records of newly diagnosed PLWH seeking care at six medical centers around Taiwan between 2009 and 2018 were reviewed. The annual trends of PLWH who had CrAg testing and cryptococcal antigenemia were examined by Cochran-Armitage test. Among PLWH with CD4 < 200 cells/µl, timing of CrAg testing was analyzed for association with 12-month all-cause mortality in Kaplan-Meier plots and in a Cox proportional hazards model after adjustments. RESULTS: Among 5372 included PLWH, 1150 (21.4%) presented with baseline CD4 < 100 cells/µl, and this proportion had decreased during the study period [from 108 (29.3%) in 2009 to 93 (22.3%) in 2018 (P = 0.039)]. The overall prevalence of cryptococcal antigenemia was 7.8% among PLWH with CD4 < 100 cells/µl, which remained stable during the 10-year study period (P = 0.356) and was 2.6% among PLWH with CD4 100-199 cells/µl. The uptake of CrAg testing had increased from 65.7% in 2009 to 78.0% in 2018 (P = 0.002) among PLWH with CD4 < 100 cells/µl. Late CrAg testing, defined by 14 days or later after HIV diagnosis, was associated with increased risk of 12-month mortality compared to early CrAg testing (adjusted hazard ratio 2.028, 95% CI 1.109-3.708). CONCLUSIONS: Burden of cryptococcosis remained high among PLWH with low CD4 lymphocyte counts in Taiwan. Uptake of CrAg screening among late HIV presenters was still suboptimal and delayed. Late CrAg testing was associated with a higher mortality.

Multicenter evaluation of four immunoassays for the performance of early diagnosis of COVID-19 and assessment of antibody responses of patients with pneumonia in Taiwan.

BACKGROUND/PURPOSE: Our study goals were to evaluate the diagnostic performance of four anti-SARS-CoV-2 antibodies tests and the differences in dynamic immune responses between COVID-19 patients with and without pneumonia. METHODS: We collected 184 serum samples from 70 consecutively qRT-PCR-confirmed COVID-19 patients at four participating hospitals from 23 January 2020 to 30 September 2020. COVID-19 pneumonia was defined as the presence of new pulmonary infiltration. Serum samples were grouped by the duration after symptom onset on a weekly basis for antibody testing and analysis. The four immunoassays: Beckman SARS-CoV-2 IgG/IgM (Beckman Test), Siemens (ADVIA Centaur®) SARS-CoV-2 Total (COV2T) (Siemens Test), SBC COVID-19 IgG ELISA (SBC Test) and EliA SARS-CoV-2-Sp1 IgG/IgM/IgA P2 Research (EliA Test) were used for detecting the SARS-CoV-2 specific antibodies. RESULTS: The sensitivity of all tests reached 100% after 42 days of symptom onset. Siemens Test, the only test detecting total anti-SARS-CoV-2 antibodies, had the best performance in the early diagnosis of COVID-19 infection (day 0-7: 77%; day 8-14: 95%) compared to the other 3 serological tests. All tests showed 100% specificity except SBC Test (98%). COVID-19 patients with pneumonia had significantly higher testing signal values than patients without pneumonia (all p values < 0.05, except EliA IgM Test). However, Siemens Test and SBC Test had highest probability in early prediction of the presence of COVID-19 pneumonia. CONCLUSION: Chronological analysis of immune response among COVID-19 patients with different serological tests provides important information in the early diagnosis of SARS-CoV-2 infection and prediction of the risk of pneumonia after infection.

Hepatitis B virus seroprevalence among HIV-infected patients receiving combination antiretroviral therapy three decades after universal neonatal hepatitis B immunization program in Taiwan.

BACKGROUND/PURPOSE: This multicenter study aimed to evaluate the seroprevalence of hepatitis B virus (HBV) and the use of combination antiretroviral therapy (cART) among patients receiving HIV care in Taiwan. METHODS: We retrospectively reviewed the medical records of HIV-infected adult patients who initiated cART at 11 designated hospitals in Taiwan between 2012 and 2016. The clinical information collected included serological profiles on HBV, hepatitis C virus (HCV), and syphilis, plasma HIV RNA load, nadir CD4 cell count, and antiretrovirals with activity against both HBV and HIV (tenofovir disoproxil fumarate [TDF], lamivudine [LAM], and emtricitabine [FTC]). RESULTS: We analyzed 1800 HIV-infected patients; 1742 (96.8%) were male and 794 (44.1%) were born after July, 1986, when nationwide universal neonatal HBV vaccination was implemented. HBsAg positive results were 11.6% (209/1800), which decreased significantly from 18.1% (182/1006) in those born before July 1986 to 3.4% (27/794) in those born after. In multivariable analysis, HBsAg positivity was significantly associated with age (adjusted odds ratio [aOR] 1.06, 95% confidence interval [CI] 1.05-1.08), CD4≧200 cells/µL (aOR 0.73, 95% CI 0.53-0.99), and HCV seropositivity (aOR 1.62, 95% CI 1.06-2.50). Of 209 HBV/HIV-coinfected patients, 31.1% started cART containing only LAM with anti-HBV activity, while 68.9% started cART containing TDF plus LAM or coformulated TDF/FTC. CONCLUSIONS: The overall prevalence of HBV/HIV coinfection remained high among HIV-infected patients in Taiwan. Despite recommendations of the HIV treatment guidelines for the management of HBV infection, a substantial proportion of HIV/HBV-coinfected patients received cART containing only LAM for HBV infection.

High rates of misidentification of uncommon Candida species causing bloodstream infections using conventional phenotypic methods.

BACKGROUND: Candidemia caused by uncommon Candida species is increasing and misidentification may compromise optimal antifungal therapy. This multicenter study aimed to evaluate the accuracy of species-level identification of uncommon Candida. METHODS: Uncommon causative species of candidemia identified in routine laboratories using CHROMagar, API-32C and VITEK-2 Yeast ID system were collected from July 2011 to June 2014. These isolates were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system and sequencing of the internal transcribed spacer and 28S rRNA gene. Susceptibility of the isolates was determined. RESULTS: Of 85 isolates evaluated, Candida guilliermondii (n = 36) was the most common, followed by Candid sake (n = 7) and Candida famata (n = 4). Using DNA-sequencing analysis as standard, none of C. sake and C. famata was correct, while VITEK MS correctly identified 10 of the 11 isolates. With the exclusion of one unspecified Candida by DNA-sequencing methods, the accuracy of conventional methods and VITEK MS was 64.3% and 86.9%, respectively (p = 0.001). Eight isolates were confirmed to be yeasts other than Candida. Compared with other Candida species, C. guilliermondii showed elevated minimal inhibitory concentration of echinocandins. CONCLUSION: Misidentification of uncommon Candida species was common using the conventional methods, especially for C. sake and C. famata. MALDI-TOF MS assisted by DNA-sequencing methods should be considered.

Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide as Maintenance Treatment in HIV/HBV-Coinfected Patients.

BACKGROUND: The efficacy and safety of switching from tenofovir disoproxil fumarate-based antiretroviral therapy to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF) has not been widely investigated in HIV/hepatitis B virus (HBV)-coinfected Asian population. METHODS: Between February and October 2018, HIV/HBV-coinfected patients who had achieved HIV viral suppression with tenofovir disoproxil fumarate-containing regimens were switched to E/C/F/TAF. Assessments of plasma HBV and HIV viral load, HBV serology, renal function, lipid profiles, and bone mineral density (BMD) were performed at weeks 24 and 48 after switch. RESULTS: A total of 274 HIV/HBV-coinfected participants were enrolled, with 12.8% testing HBeAg-positive and 94.2% having plasma HBV DNA <20 IU/mL at baseline. At weeks 24 and 48, 92.7% and 89.8% achieved plasma HBV DNA <20 IU/mL; 4.7% and 5.1% had HBV DNA ≥20 IU/mL; and 2.6% and 5.1% had no data, respectively. At weeks 24 and 48, 95.6% and 94.2% of participants maintained HIV RNA <50 copies/mL, respectively. Compared with baseline, the median urine ß2-microglobulin-to-creatinine ratio at week 48 decreased significantly from 165 to 90 µg/g (P < 0.001). The mean BMD of the spine and hip improved at week 48 (+1.77% and +1.33%, respectively). Significantly higher lipid profiles were observed after switch to E/C/F/TAF. Thirteen (4.7%) patients withdrew from the study before week 48, with 7 (2.6%) patients because of adverse effects. CONCLUSIONS: Switch to E/C/F/TAF maintained HBV and HIV viral suppression and resulted in the improvement of proteinuria and BMD of the spine and hip but increased lipid levels in HIV/HBV-coinfected patients at week 48.

Multicenter evaluation of two chemiluminescence and three lateral flow immunoassays for the diagnosis of COVID-19 and assessment of antibody dynamic responses to SARS-CoV-2 in Taiwan.

This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4-99.0%), Abbott Test (94.0%, 89.1-96.8%), Wondfo Test (91.4%, 85.8-94.9%), ASK Test (97.4%, 93.4-99.0%), and Dynamiker Test (90.1%, 84.3-94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3-99.7%) for the Roche Test, 97.9% (95% CI, 94.8-99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1-100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.