Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Self-Reported Health-Related Quality of Life and Residual Symptoms among Virologically Suppressed People Living with HIV in the Era of Single-Tablet Regimens in Taiwan: A Cross-Sectional Study.

This study assessed the health-related quality of life (HRQoL) and residual symptom burden among virologically suppressed people living with human immunodeficiency virus (HIV) (PLWH) using a single-tablet regimen in Taiwan. This cross-sectional study administered a self-reported online survey between July and October 2021 to anonymised virologically suppressed PLWH aged ≥20 years. Demographic, HIV-related variables, EuroQol-5-dimensions (EQ-5D), visual analogue scale (VAS), and HIV Symptom Index were analysed. Bivariate analyses were performed to compare HRQoL differences between PLWH and non-PLWH. Among 120 PLWH, 80.9% had HIV diagnosis for <15 years, median antiretroviral therapy (ART) duration of 7.0 years (Q1-Q3:4.0-11.0), and 62.5% had ≥1 comorbidity. The most common comorbidities were depression (26.7%) and hyperlipidaemia (15.8%). About one-fifth of PLWH received constant family support (25.8%) and peer support (21.7%). Married individuals or individuals with higher incomes had significantly better family support status. There was no significant difference across the five dimensions between PLWH and non-PLWH. PLWH perceived being bothered by fatigue/lack of energy (63.3%), sleep difficulties (63.3%), feeling sad/low/unhappy (51.7%), and appearance changes (51.7%). PLWH could achieve similar HRQoL as non-PLWH with stable treatment, highlighting an opportunity to focus on person-centred holistic care beyond HIV, especially on the psychological aspect, for the best possible HRQoL for PLWH.

Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Respiratory virus coinfections during the COVID-19 pandemic: epidemiologic analysis and clinical outcomes from the Phase 2/3 molnupiravir trial (MOVe-OUT).

This exploratory post hoc analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, n = 302) and May 2021 to October 2021 (Phase 3, n = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups. IMPORTANCE: Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program.

BACKGROUND/AIMS: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION: Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan.

BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.

Preventing and controlling intra-hospital spread of COVID-19 in Taiwan - Looking back and moving forward.

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan.

Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV.

BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

Optimal Frequency of Hepatitis C Virus (HCV) RNA Testing for Detection of Acute HCV Infection Among At-risk People With Human Immunodeficiency Virus: A Multicenter Study.

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.

Rapid Escherichia coli Cloned DNA Detection in Serum Using an Electrical Double Layer-Gated Field-Effect Transistor-Based DNA Sensor.

In this study, a rapid diagnosis platform was developed for the detection of Escherichia coli O157:H7. An electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) as a point-of-care testing device is demonstrated with its high sensitivity, portability, high selectivity, quick response, and ease of use. The specially designed ssDNA probe was immobilized on the extended gate electrode to bind the target complementary DNA segment of E. coli, resulting in a sharp drain current change within minutes. The limit of detection for target DNA is validated to a concentration of 1 fM in buffer solution and serum. Meanwhile, the results of a Kelvin probe force microscope were shown to have reduced surface potential of the DNA immobilized sensors before and after the cDNA detection, which is consistent with the decreased drain current of the BioFET. A 1.2 kb E. coli duplex DNA synthesized in plasmid was sonicated and detected in serum samples with the sensor array. Gel electrophoresis was used to confirm the efficiency of sonication by elucidating the length of DNA. Those results show that the EDL-gated BioFET system is a promising platform for rapid identification of pathogens for future clinical needs.

Longitudinal neutralizing antibody responses after SARS-CoV-2 infection: A convalescent cohort study in Taiwan.

BACKGROUND: Understanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration. METHODS: A cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population. RESULTS: A total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11-3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33-0.92). CONCLUSIONS: Neutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations.

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.

Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naïve patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry.

BACKGROUND: Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. METHODS: The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. RESULTS: Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. CONCLUSIONS: In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.

Clinical assessment of SARS-CoV-2 infectivity by rapid antigen test compared with virus isolation.

Although real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) remains as a golden standard for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it can not be easily expanded to large-scaled screening during outbreaks, and the positive results do not necessarily correlate with infectious status of the identified subjects. In this study, the performance of Vstrip® RV2 COVID-19 Antigen Rapid Test (RAT) and its correlation with virus infectivity was examined by virus culture using 163 sequential respiratory specimens collected from 26 SARS-CoV-2 infected patients. When the presence of cytopathic effects (CPE) in cell culture was used as a reference method for virus infectivity, the sensitivity, specificity and accuracy of Vstrip® RV2 COVID-19 Antigen Rapid Test was 96.43%, 89.63%, and 90.8%, respectively. The highest Ct value was 27.7 for RdRp gene and 25.79 for E gene within CPE-positive samples, and the highest Ct value was 31.9 for RdRp gene and 29.1 for E gene within RAT positive samples. When the Ct values of specimens were below 25, the CPE and RAT results had high degree of consistency. We concluded that the RAT could be a great alternative method for determining the infectious potential of individuals with high viral load.

Correlation of adverse effects and antibody responses following homologous and heterologous COVID19 prime-boost vaccinations.

BACKGROUND: Studies correlating reactogenicity and immunogenicity of COVID-19 vaccines are limited to BNT162b2, with inconsistent results. We investigated whether adverse reactions after other COVID-19 vaccines reliably predict humoral responses. METHODS: Adult volunteers were recruited for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines administered either 4 or 8 weeks apart. Adverse effects were routinely solicited and recorded by subjects in a standard diary card for up to 84 days post booster vaccination. Anti-SARS-CoV-2 IgG titers were measured pre- (visit 1), and post-booster dose at days 14 (visit 2) and 28 (visit 3). RESULTS: A total of 399 participants (75% women) with a median age of 41 (interquartile range, 33-48 IQR) years were included. Vaccine-induced antibody titers at days 14 and 28 were significantly higher among subjects who reported local erythema, swelling, pain, as well as systemic fever, chills, headache, myalgia, arthralgia, fatigue compared to those who did not experience local or systemic reactogenicity. Post-vaccination humoral responses did not correlate with the occurrence of skin rash and correlated weakly with gastrointestinal symptoms. A significant correlation between post-vaccination peak body temperature and anti-SARS-CoV-2 spike IgG at Day 14, independent of vaccine type and schedule, was found. CONCLUSION: Specific symptoms of reactogenicity such as post-vaccination injection site pain, swelling, erythema and fever, myalgia and fatigue are significantly predictive of the magnitude of the anti-SARS-CoV-2 antibody response.

Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290.

Safety and Immunogenicity of a Heterologous Booster of Protein Subunit Vaccine MVC-COV1901 after Two Doses of Adenoviral Vector Vaccine AZD1222.

We report the safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 (Group A) or 24 (Group B) weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). The administration of the MVC-COV1901 vaccine as a booster dose in both groups was generally safe. There were no serious adverse events related to the intervention as adverse events reported were "mild" or "moderate" in nature. In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, those who were vaccinated within 12 weeks after the last AZD1222 dose (Group A) had anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers which were 14- and 6.5-fold increased, respectively, when compared to the titer levels on the day of the booster dose. On the other hand, fold-increase a month post-booster in people who had a booster 24 weeks after the last AZD1222 dose (Group B) were 19.5 and 14.0 times for anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers, respectively. Among those who were vaccinated within 12 weeks after the last AZD1222 dose, we also observed 5.2- and 5.6-fold increases in neutralizing titer levels against ancestral strain and Omicron variant pseudovirus after the booster dose, respectively. These results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222. Furthermore, regardless of the dosing schedule, the combination of AZD1222 primary series and MVC-COV1901 booster can be cost-effective and suitably applied to low- and middle-income countries (LMIC).

Serological response after COVID-19 mRNA-1273 booster dose in immunocompromised patients, Taiwan, July to August 2021.

BACKGROUND: Whether immunocompromising conditions affect the immunogenicity of COVID-19 booster vaccination remains a concern, which impedes the vaccination campaign in people most vulnerable to COVID-19-associated morbidity and mortality. We aimed to evaluate the effect of immune dysfunction on immunogenicity of homologous and heterologous prime-boost COVID-19 vaccination. METHODS: Between July and August, 2021, 399 participants were randomized to receive ChAdOx1/ChAdOx1 8 weeks apart, ChAdOx1/mRNA-1273 8 weeks apart, ChAdOx1/mRNA-1273 4 weeks apart, and mRNA-1273/mRNA-1273 4 weeks apart. The anti-SARS-CoV-2 spike IgG antibody titers on the day before booster vaccination and 4 weeks after booster vaccination were compared between participants with and without immunocompromising conditions. RESULTS: Among ChAdOx1-primed participants, a trend of lower anti-SARS-CoV-2 spike IgG titers before booster vaccination were found in participants with autoimmune diseases (geometric means, 34.76 vs. 84.25 binding antibody units [BAU]/mL, P = 0.173), compared to those without. Participants receiving immunosuppressants and/or immunomodulators had significant lower anti-SARS-CoV-2 spike IgG titers before booster vaccination than those without (geometric means, 36.39 vs. 83.84 BAU/mL; P = 0.001). Among mRNA-1273-boosted participants, anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination were similar across all the strata. Participants with autoimmune diseases and receiving immunosuppressants and/or immunomodulators, had numerically lower anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination compared to those without (geometric means, 1474.34 vs. 1923.23 and 1590.61 vs. 1918.38 BAU/mL; P > 0.05). CONCLUSION: The immunogenicity of prime vaccination with ChAdOx1 decreased by immune dysfunction, but enhanced after receiving boost vaccination with mRNA-1273. Our study results support the efficacy of mRNA-1273 booster dose among immunocompromised hosts.

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.