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.

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.

Stool microbiota analysis for abundance of genus Klebsiella among adults and children in endemic area for community Klebsiella pneumoniae infection.

BACKGROUND: Invasive Klebsiella pneumoniae syndrome is a significant endemic disease in Taiwan. Intestinal colonization of virulent clones that cause this phenomenon has been demonstrated in asymptomatic adults. Comparisons of healthy adults and children with stool K. pneumoniae colonization have rarely been reported. We aimed to evaluate the frequency and abundance of K. pneumoniae in the stool of adults and children by stool microbiota analysis. METHODS: Healthy volunteers and their children without antibiotic exposure within 3 months were recruited in a Taiwanese medical center. Stool samples were sent for gut microbiota analysis, using amplification of V3-V4 hypervariable regions of 16sRNA followed by high-throughput sequence. Rectal/stool swabs were sent for K. pneumoniae culture and identification by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: Fifty-five adults with a mean age of 46.9 years (range, 23.1-72.1 years) and 20 children with a mean age of 2.3 years (range, 0.9-5.8) were enrolled, and 29 adults and 6 children had positive K. pneumoniae swabs. Children had lower microbiota diversity than adults, including higher abundance of phylum Actinobacteria and Proteobacteria, and lower Bacteriodetes. For genus comparison, higher abundance of Escherichia, Streptococcus, Enterococcus and Bifidobacterium were found in children, but the composite abundance of Klebsiella in adults (median: 0.0156, range: 0-0.031) and in children (median: 0.0067, range: 0-0.043) were similar. Klebsiella abundance was significantly higher in participants with positive swabs (p < 0.0001). Klebsiella-positive swabs were strongly negatively correlated with Enterobacter spp. (p < 0.0001), but no known demographic factors correlated with Klebsiella-positive swabs. CONCLUSION: Klebsiella species are present in young children, and the abundance is similar in adults and children. Positive swabs correlate strongly with higher abundance in microbiota analysis.

Evaluation of the synergistic effect of eravacycline and tigecycline against carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a substantial healthcare challenge. This study assessed the in vitro efficacy of selected antibiotic combinations against CRKP infections. METHODS: Our research involved the evaluation of 40 clinical isolates of CRKP, with half expressing Klebsiella pneumoniae carbapenemase (KPC) and half producing Metallo-ß-lactamase (MBL), two key enzymes contributing to carbapenem resistance. We determined the minimum inhibitory concentrations (MICs) of four antibiotics: eravacycline, tigecycline, polymyxin-B, and ceftazidime/avibactam. Synergistic interactions between these antibiotic combinations were examined using checkerboard and time-kill analyses. RESULTS: We noted significant differences in the MICs of ceftazidime/avibactam between KPC and MBL isolates. Checkerboard analysis revealed appreciable synergy between combinations of tigecycline (35%) or eravacycline (40%) with polymyxin-B. The synergy rates for the combination of tigecycline or eravacycline with polymyxin-B were similar among the KPC and MBL isolates. These combinations maintained a synergy rate of 70.6% even against polymyxin-B resistant isolates. In contrast, combinations of tigecycline (5%) or eravacycline (10%) with ceftazidime/avibactam showed significantly lower synergy than combinations with polymyxin-B (P < 0.001 and P = 0.002, respectively). Among the MBL CRKP isolates, only one exhibited synergy with eravacycline or tigecycline and ceftazidime/avibactam combinations, and no synergistic activity was identified in the time-kill analysis for these combinations. The combination of eravacycline and polymyxin-B demonstrated the most promising synergy in the time-kill analysis. CONCLUSION: This study provides substantial evidence of a significant synergy when combining tigecycline or eravacycline with polymyxin-B against CRKP strains, including those producing MBL. These results highlight potential therapeutic strategies against CRKP infections.

Burden of respiratory syncytial virus in older adults in Taiwan: An expert perspective on knowledge gaps.

The burden of respiratory syncytial virus (RSV) infection among older adults in Taiwan is not well understood due to a scarcity of published epidemiological data. Nonetheless, the increasing proportion of older adults is anticipated to translate to increased burden of RSV infection, presenting a challenge to the healthcare system. Thus, an expert meeting was convened among a panel of infectious disease specialists from Taiwan to evaluate the existing local evidence and data gaps related to RSV infection in older adults (aged ≥50 years), and propose steps to generating evidence on disease burden among this population. Overall, there are few studies on the clinical and economic burden of RSV infection in Taiwan, and existing data are limited by small sample sizes and highly selected populations. Inconsistent RSV testing practices among older adults contribute to under-diagnosis and under-reporting, driven by limitations to reimbursement policies that discourage proactive RSV testing in older adults, and the lack of appropriate, targeted RSV treatment. Crucially, the paucity of epidemiological data may perpetuate a lack of awareness of RSV among clinicians and the public, hinder investments into RSV testing at a policymaker level, and thereby impede implementation of consistent diagnostic practices, precluding a deeper understanding of RSV. To overcome these challenges, it is imperative to prioritize generation of epidemiological data to establish the burden of RSV infection among older adults in Taiwan. Such data would also support a multi-stakeholder group in assessing the impact of future RSV-related interventions, such as educational initiatives and preventative strategies including vaccines.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in treatment-naïve and treatment-experienced people with HIV: Findings from the Asia cohort of the BICSTaR study.

BACKGROUND: The ongoing, observational BICSTaR (BICtegravir Single Tablet Regimen) cohort study is evaluating real-world effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV across 14 countries over 24 months. We present 12-month data from the BICSTaR Asia cohort. METHODS: Data were pooled from retrospective and prospective cohorts of antiretroviral therapy (ART)-naïve (hereafter, TN) and ART-experienced (hereafter, TE) people with HIV (aged ≥21 years) receiving B/F/TAF in routine clinical care in the Republic of Korea, Singapore, and Taiwan. Analyses included effectiveness (primary endpoint: HIV-1 RNA <50 copies/ml, missing = excluded analysis), CD4 count, CD4/CD8 ratio, safety, treatment persistence, and patient-reported outcomes (prospective group). RESULTS: The analysis population included 328 participants (80 retrospective, 248 prospective; 65 TN, 263 TE). Participants were predominantly male (96.9% TN, 93.2% TE) with ≥1 comorbidity (52.3% TN, 57.8% TE); median age (years) was 31 (TN) and 42 (TE). Following 12 months of B/F/TAF, HIV-1 RNA was <50 copies/ml in 98.2% (54/55) of TN and 97.0% (227/234) of TE participants. Median (Q1, Q3) CD4 cell count increased by +187 (119, 291) cells/µl in the TN group (p < 0.001) and remained stable (+8 [-91, 110] cells/µl) in the TE group. B/F/TAF persistence was high in the prospective group, with 1/34 (2.9%) TN and 5/214 (2.3%) TE participants discontinuing treatment within 12 months. Drug-related adverse events occurred in 5.8% (19/328) of participants, leading to treatment discontinuation in 0.6% (2/328). CONCLUSIONS: Real-world evidence from BICSTaR supports the effectiveness, safety and tolerability of B/F/TAF in people with HIV in Asia.

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.

Remdesivir-Induced Bradycardia and Mortality in SARS-CoV-2 Infection, Potential Risk Factors Assessment: A Systematic Review and Meta-Analysis.

Background: The efficacy of remdesivir in reducing disease severity among COVID-19-infected patients has been established, but concerns have emerged regarding the potential side effects of bradycardia. The aim of this study was to investigate the association between remdesivir-induced bradycardia and mortality, while also identifying the related risk factors. Materials and methods: The PubMed/Medline, Cochrane Central and ClinicalTrials.gov databases were searched. Randomized controlled trials and prospective or retrospective cohort studies were included (through 14 July 2023). The random-effects model was implemented using Comprehensive Meta-Analysis software version 3.0 to examine the outcomes. Results: A total of 12 prospective or retrospective studies involving 7674 patients were analyzed. The primary outcomes revealed a significant association between remdesivir administration and bradycardia development (Odds ratio = 2.556, 95% CI = 2.049-3.188, p < 0.001). However, no statistically significant increase in the mortality rate was observed among patients with bradycardia during remdesivir treatment (Odds ratio = 0.872, 95% CI = 0.483-1.576, p = 0.651). The secondary outcome demonstrated a significant association between chronic kidney disease (CKD) and remdesivir-induced bradycardia (OR: 1.251, 95% CI: 1.003-1.561, p = 0.047). Moreover, patients with obesity (OR = 1.347, 95% CI = 1.098-1.652, p = 0.004) were more likely to experience remdesivir-induced bradycardia. Conclusions: Although a higher risk of bradycardia occurred during remdesivir treatment, the occurrence of remdesivir-induced bradycardia did not lead to higher mortality. Our study also identified patients with obesity and CKD as high-risk subgroups for experiencing bradycardia during remdesivir treatment.