Mycoplasma genitalium infection and resistance-associated mutations to macrolides and fluoroquinolones among high-risk patients in Taiwan.

BACKGROUND: Mycoplasma genitalium is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of M. genitalium infection and antimicrobial resistance is warranted. METHODS: Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for M. genitalium infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of M. genitalium to fluoroquinolones, macrolides, and tetracycline were investigated. RESULTS: During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had M. genitalium infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with M. genitalium infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more M. genitalium infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p < 0.01) was found in PWoH. CONCLUSIONS: Among high-risk populations, the prevalence of M. genitalium infection was 8.1%. The overall genotypic resistance of M. genitalium to macrolides and fluoroquinolones was moderately high in Taiwan. Detection of M. genitalium infection and antimicrobial resistance is warranted to ensure resistance-guided antimicrobial treatments to be administered.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.

Weight and metabolic changes among virally suppressed people with HIV who switched to co-formulated bictegravir/emtricitabine/tenofovir alafenamide.

OBJECTIVES: We aimed to investigate the evolution of weight, lipid profiles, and glucose homeostasis among virally suppressed people with HIV (PWH) who switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). METHODS: PWH with viral suppression who switched to BIC/FTC/TAF in Taiwan between October 2019 and May 2021 were followed for 96 weeks to examine changes in weight, lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG)), and glycated hemoglobin (HbA1c) levels. RESULTS: 889 PWH with an average weight of 72.1 kg at baseline were included. At week 96, more than 95% of PWH consistently maintained plasma HIV RNA load <50 copies/mL at each 24-week interval of follow-up, while the weight change was small (+0.7 kg, P < 0.0001), although statistically significant. Baseline levels of TC, LDL-C, HDL-C, TG, and HbA1c were 191.8 mg/dL, 114.2 mg/dL, 48.9 mg/dL, 174.3 mg/dL, and 5.31%, respectively. After 96 weeks, changes were observed in TC (-11.6 mg/dL, P < 0.0001), LDL-C (-3.4 mg/dL, P = 0.0084), HDL-C (+0.6 mg/dL, P = 0.1089), TG (-30.2, P < 0.0001), and HbA1c (+0.12%, P < 0.0001). A 5% or more weight gain was associated with age of 30-40 years, normal weight at baseline, and prior use of non-integrase inhibitors or tenofovir disoproxil fumarate. Obesity was associated with development of both dyslipidaemia and diabetes mellitus after switch. CONCLUSIONS: Stable switch to BIC/FTC/TAF maintained high rates of viral suppression and had a small effect on weight and metabolic changes in virally suppressed PWH. Follow-up of the weight and metabolic changes is warranted in PWH on long-term antiretroviral therapy.

Effectiveness of second-generation integrase strand-transfer inhibitor-based regimens for antiretroviral-experienced people with HIV who had viral rebound.

BACKGROUND: Antiretroviral regimens containing a second-generation integrase strand-transfer inhibitor (INSTI) plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) are the recommended therapy for people with HIV (PWH) who are antiretroviral-naïve or on stable antiretroviral therapy (ART) with viral suppression. Real-world data on the virologic effectiveness of co-formulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among PWH with virologic failure while receiving other ART remain sparse. METHODS: We retrospectively reviewed the medical records of PWH who had viral rebound with plasma HIV RNA >1000 copies/mL and were switched to either dolutegravir combined with 2 NRTIs or BIC/FTC/TAF. The primary end point was re-achieving viral suppression within the first 48 weeks of switch. The association between NRTI-related resistance-associated mutations (RAMs) and virologic effectiveness was examined. RESULTS: Seventy-nine PWH with viral rebound while receiving other antiretroviral regimens were included. Within the first 48 weeks of switch, the overall probability of re-achieving viral suppression was 79.7% (82.5% [33/40] and 76.9% [30/39] for BIC/FTC/TAF and dolutegravir-based regimens, respectively, p = 0.78). PWH with a higher CD4 lymphocyte count (adjusted odds ratio, per 100-cell/mm3 increase, 1.41; 95% confidence interval, 1.02-1.95) were more likely to re-achieve viral suppression. Among PWH switching to BIC/FTC/TAF who had pre-existing RAMs to NRTIs before switch, 14 of 15 (93.3%) successfully achieved viral suppression. CONCLUSIONS: Switching to BIC/FTC/TAF and dolutegravir-based regimens could re-achieve viral suppression in four-fifth of the PWH who experienced viral rebound during treatment with other antiretroviral regimens. Pre-existing NRTI-related RAMs did not have adverse impact on the effectiveness of dolutegravir combined with 2 NRTIs or BIC/FTC/TAF.

Character Strengths Use in Diabetes Self-management Scale: Development and psychometric testing.

AIMS: To develop and psychometrically test Character Strengths Use in Diabetes Self-management Scale in people with type 2 diabetes. DESIGN: Cross-sectional design. METHODS: Based on literature reviews and examination by experts, a 20-item scale was developed and administered to 350 participants with type 2 diabetes who were enrolled from two endocrine clinics by convenience sampling in Taiwan. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), concurrent and predictive validity as well as reliability were used to examine the psychometric characteristics of the scale. Data were collected from November 2021 to March 2022. RESULTS: EFA and CFA supported a 12-item scale with three factors, namely learning proactively, taking on challenges and thinking positively, fit the data well. The total score of the 12-item scale significantly and positively correlated with diabetes-specific quality of life, and significantly and negatively correlated with baseline and 9-month haemoglobin A1c levels. Cronbach's α for overall scale and subscales ranged between .78 and .91. CONCLUSION: The 12-item Character Strengths Use in Diabetes Self-management Scale demonstrated satisfactory validity and reliability in people with type 2 diabetes. IMPACT: Nurses could apply this new scale to identify the degree of using character strengths in self-management in people with type 2 diabetes; accordingly, character strength-based interventions could be provided to improve self-management in such patients with diabetes. Furthermore, the 12-item Character Strengths Use in Diabetes Self-management Scale has the potential to be used to measure the effectiveness of strength-based interventions in people with Type 2 diabetes. PATIENT OR PUBLIC CONTRIBUTION: Five patients with type 2 diabetes were invited to take the original 20-item scale to evaluate the clarity, readability and comprehensiveness of the 20 items.

Effect of Chair Yoga Therapy on Functional Fitness and Daily Life Activities among Older Female Adults with Knee Osteoarthritis in Taiwan: A Quasi-Experimental Study.

This study aims to examine the effectiveness of chair yoga therapy on improving functional status and daily life activity scores in older female adults with knee osteoarthritis living in the community. A quasi-experimental design was adopted. In total, 85 female participants with knee osteoarthritis were assigned to the chair yoga therapy intervention group (n = 43) or the comparison (n = 42) group. A 12-week chair yoga exercise program was provided to the intervention group two times per week from January to April 2020. The primary outcomes, which include changes in physical functional ability, body mass index, and biophysiological indicators, were evaluated for all participants in the pre- and post-measures time periods. The analysis shows that the participants had a significantly higher level of functional fitness and daily life activity scores after the chair yoga intervention. This finding indicates that the chair yoga program was effective in improving the functional fitness and daily life activity scores of community-dwelling elderly females with knee osteoarthritis.

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

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

MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of SMN1 is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, Mir34 family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.

Patient-reported outcomes among virally suppressed people living with HIV after switching to Co-formulated bictegravir, emtricitabine and tenofovir alafenamide.

BACKGROUND: While some evidence has suggested the benefits of co-formulated bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in improving the quality of life of people living with HIV (PLWH), patient-reported outcome studies that focus on Asian population remain scarce. We aimed to determine the changes in HIV-related symptom burden in virally-suppressed PLWH switching to B/F/TAF in a real-world setting. METHODS: PLWH on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV RNA <200 copies/mL who decided to switch to B/F/TAF were eligible for the study. Participants' experience with 20 symptoms were assessed using HIV Symptom Index at baseline and weeks 24 and 48. Responses were dichotomized in two ways: 1) present vs. not present; and 2) bothersome vs. not bothersome, and compared across time points. RESULTS: Six hundred and thirty participants (prior regimen, 94.4% integrase inhibitor-based) who completed week 48 visit were included in the analysis. Forty-eight weeks after switching to B/F/TAF, six symptoms were significantly less prevalent, and seven symptoms were significantly less bothersome. Improvement was more pronounced in participants whose prior regimen was elvitegravir-based versus dolutegravir-based. Logistic regression results showed that prior dolutegravir-based ART and pre-existing diabetes independently predicted improvement in diarrhea/loose bowels and muscle aches/joint pain, respectively. Despite the overall improvement, some symptoms persisted in a substantial proportion of participants. CONCLUSIONS: Virally-suppressed PLWH might benefit from a regimen switch to B/F/TAF to reduce the prevalence and level of bother of HIV-related symptoms. Nevertheless, additional multidisciplinary interventions are warranted to further alleviate the symptom burden of PLWH.

Risky sexual practices and hepatitis C viremia among HIV-positive men who have sex with men in Taiwan.

BACKGROUND: Understanding the risk behaviors associated with sexually-transmitted hepatitis C virus (HCV) infection among men who have sex with men (MSM) may inform the public health policies and interventions aiming to achieve HCV microelimination. METHODS: HIV-positive MSM who had one of the following conditions were enrolled to undergo face-to-face questionnaire interviews to collect information on their sexual practices in the past 12 months: (1) elevation of aminotransferases in the past 6 months; (2) acquisition of sexually transmitted infections in the past 6 months; and (3) previous HCV infections. Plasma HCV RNA were tested at enrolment and every 3 months during follow-up. Baseline characteristics and risky behaviors were compared to identify factors associated with HCV viremia between HCV-viremic MSM and HCV-aviremic MSM in multivariate analysis. RESULTS: Among 781 MSM with a median age of 36 years, 57 (7.3%) had HCV viremia and 724 (92.7%) no HCV viremia during follow-up. A high proportion (38.9%) of the participants reported having used recreational drugs in the past 12 months, with 34.4% of them having slamming, but only 4.8% reported having shared their injection equipment. In multivariate analysis, use of recreational drugs (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.96), having participated in group sex (aOR, 2.35; 95% CI 1.24-4.40) and having had condomless receptive anal intercourse (aOR, 1.97; 95% CI 1.07-3.62) were significantly associated with HCV viremia. CONCLUSION: Among high-risk HIV-positive MSM, use of recreational drugs and risky sexual contacts were associated with HCV viremia, suggesting the mucosal contacts as the major route of HCV transmission.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Virological responses to tenofovir-alafenamide-containing antiretroviral therapy in people living with HIV co-infected with lamivudine-resistant or lamivudine-susceptible hepatitis B virus.

BACKGROUND: Data on the effectiveness of tenofovir alafenamide (TAF) against lamivudine-resistant (LAM-R) hepatitis B virus (HBV) among patients co-infected with human immunodeficiency virus (HIV) and HBV are limited. METHODS: Between April and December 2018, HIV-positive patients co-infected with LAM-R or lamivudine-susceptible (LAM-S) HBV who switched from tenofovir-disoproxil-fumarate-containing antiretroviral therapy (ART) to TAF-containing ART were followed for 96 weeks. Plasma HBV and HIV loads, HBV serological markers, and liver function before and after the switch were analysed. RESULTS: In total, 182 patients co-infected with HIV and HBV were included in this study: 45 with LAM-R HBV and 137 with LAM-S HBV. At baseline, 28.9% and 7.4% of patients in the LAM-R and LAM-S groups, respectively, tested positive for hepatitis B virus envelope antigen (HBeAg) (P<0.001), and the respective percentages of patients who had achieved plasma HBV DNA <20 IU/mL were 95.5% and 97.1%. At weeks 48 and 96, 100% and 94.9% of patients in the LAM-R group, respectively, and 97.1% and 95.6% of patients in the LAM-S group, respectively, maintained plasma HBV DNA <20 IU/mL. Lamivudine resistance of HBV and baseline hepatitis B virus surface antigen (HBsAg) level were associated with HBsAg decrement at week 96 at a degree of 0.25 log10 IU/mL [95% confidence interval (CI) 0.059-0.246] and 0.22 log10 IU/mL (per 1-log10IU/mL increase, 95% CI 0.018-0.101), respectively. At week 96, 2.2% (4/182) of patients had HBsAg loss; no patients in the LAM-R group and 25.0% (2/8) of patients in the LAM-S group had HBeAg seroconversion. CONCLUSIONS: Switching to TAF-containing regimens maintained high rates of HBV viral suppression in patients co-infected with either LAM-R or LAM-S HBV. The decrease in HBsAg was minimal, and HBsAg seroconversion occurred infrequently.

Low-level viraemia and virologic failure among people living with HIV who received maintenance therapy with co-formulated bictegravir, emtricitabine and tenofovir alafenamide versus dolutegravir-based regimens.

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.

The journey of embracing life: Mothers' perspectives of living with their children with retinoblastoma.

PURPOSE: This study aimed to explore the experience and views of mothers with children who have been diagnosed with retinoblastoma. DESIGN AND METHODS: A descriptive qualitative study was conducted in the period of 2019-2021. Interviews were conducted with 21 mothers of children diagnosed with retinoblastoma in Indonesia. Data were collected by semi-structured interviews and examined by content analysis. RESULTS: Mothers evolved from a sense of unacceptability to accepting challenges and gaining inner strength. Three themes were identified: 1) physical and psychological suffering, 2) awareness of changes and demands, and 3) keep moving forward. Mothers developed positive adaptive mechanisms for coping with the problems associated with having a child with retinoblastoma. Psychological adjustment and religious beliefs were key elements in their journeys toward embracing life in the moment. CONCLUSION: Findings illuminated psychological adaptation and coping strategies of mothers with seriously ill children and highlighted how difficulties and cultural norms shaped the adaptative process. Religion and health beliefs played varied and important roles in helping mothers to manage their stress and enhance their coping strategies. PRACTICE IMPLICATIONS: Our findings revealed that it is important to routinely assess social support, traditional health beliefs, and spirituality on mothers, facilitate mentoring to help mothers find their inner strengths, and develop intervention programs designed to promote psychological adjustment without delaying treatment.

Hepatitis C microelimination among people living with HIV in Taiwan.

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

Three-Stage Pooled Plasma Hepatitis C Virus RNA Testing for the Identification of Acute HCV Infections in At-Risk Populations.

Timely diagnosis and treatment of hepatitis C virus (HCV) infection may prevent its transmission. We evaluated the performance and cost reductions of the pooled plasma HCV RNA testing strategy to identify acute HCV infections among people living with HIV (PLWH). PLWH with sexually transmitted infections, elevated aminotransferases within the past 6 months or past HCV infections (high-risk) and those without (low-risk) were enrolled prospectively. Participants underwent three-stage pooled plasma HCV RNA testing every 12 to 24 weeks until detection of HCV RNA or completion of a 48-week follow-up. The three-stage strategy combined 20 individual specimens into a stage 1 pool, 5 individual specimens from the stage 1 pool that tested positive for HCV RNA in the stage 2 mini-pool, followed by testing of individual specimens of the stage 2 mini-pool tested positive for HCV RNA. A simulation was constructed to investigate the cost reductions and pooled sensitivity and specificity under different combinations of HCV prevalence and pool/mini-pool sizes. Between June 25, 2019 and March 31, 2021, 32 cases of incident HCV viremia were identified in 760 high-risk PLWH that were enrolled 834 times, giving an incidence rate of 56.6 per 1000 person-years of follow-up (PYFU). No cases of HCV viremia were identified in 557 low-risk PLWH during a total of 269.2 PYFU. Simulation analysis suggested that this strategy could reduce HCV RNA testing cost by 50% to 86% with HCV viremia prevalence of 1% to 5% and various pooled sizes despite compromised pooled sensitivity. This pooled plasma HCV RNA testing strategy is cost-saving to identify acute HCV infections in high-risk populations with HCV viremia prevalence of 1% to 5%. IMPORTANCE Our three-stage pooled plasma HCV RNA testing successfully identified HCV viremia in high-risk PLWH with a testing cost reduction of 84.5%. Simulation analysis offered detailed information regarding the selection of pool and mini-pool sizes in settings of different HCV epidemiology and the performance of HCV RNA testing to optimize the cost reduction.

Sexually-transmitted hepatitis C virus reinfections among people living with HIV in Taiwan: the emerging role of genotype 6.

Hepatitis C virus (HCV) reinfections after successful treatment with direct-acting antivirals (DAAs) pose a significant challenge to HCV elimination, especially among high-risk people living with HIV (PLWH). In this study, PLWH who had achieved HCV viral clearance with DAAs were included between January 2018 and June 2021. PLWH having acquired HCV infections after 2017 were classified as "recent-infection group," and those before 2017 as "remote-infection group," and the incidences of HCV reinfection were compared between two groups. Clinical and behavioural characteristics were evaluated to identify associated factors with HCV reinfection. A total of 284 PLWH were included: 179 in the recent-infection group and 105 in the remote-infection group. After a median follow-up of 2.32 years (interquartile range [IQR], 0.13-3.94), the overall incidence of HCV reinfection was 5.8 per 100 person-years of follow-up (PYFU). The incidence in the recent-infection group was significantly higher than that in the remote-infection group (9.8 vs. 0.4 per 100 PYFU, p < 0.001). The leading HCV genotypes before DAA treatment were genotypes 2 (31.0%), 1b (26.8%), and 6 (21.8%); however, genotype 6 (58.8%) became predominant upon reinfection. Younger age (adjusted odds ratio [aOR] per 1-year increase, 0.95; 95% CI, 0.90-0.99), condomless receptive anal sex (aOR, 14.5; 95% CI, 2.37-88.8), rimming (aOR, 3.87; 95% CI, 1.14-13.1), and recent syphilis (aOR, 2.73; 95% CI, 1.26-5.91) were linked to HCV reinfections. In conclusion, PLWH acquiring HCV after 2017 had a significantly higher risk for sexually-transmitted HCV reinfections. The predominance of HCV genotype 6 reinfections suggests possible on-going clustered HCV infections among at-risk PLWH.

Incidence of low-level viremia and its impact on virologic failure among people living with HIV-1 who switched to elvitegravir-based antiretroviral therapy.

OBJECTIVES: We aimed to investigate the incidence of low-level viremia (LLV) and its impact on virologic failure (VF) in people living with HIV (PLWH) on stable antiretroviral therapy (ART) who switched to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/c/FTC/TAF). METHODS: PLWH aged 18 years or older who had received ART with plasma HIV RNA load (PVL) <50 copies/mL for 6 months or longer and switched to EVG/c/FTC/TAF between March and October 2018 were retrospectively included. The incidence of LLV (defined as PVL of 50-999 copies/mL) and VF (PVL ≥1000 copies/mL) was calculated and represented by Kaplan-Meier plots. The generalised estimating equation model was constructed to identify factors associated with LLV and VF. Resistance-associated mutations were determined using population sequencing. RESULTS: A total of 1078 PLWH were included. The incidence rates of LLV and VF after the switch to EVG/c/FTC/TAF were 3.5 and 0.8 events per 100 person-years of follow-up, respectively, whereas the respective cumulative incidence of LLV and VF reached 11.7% and 2.9% within 3 years of follow-up. LLV was associated with any LLV episode before or after the switch and prior exposure to integrase strand transfer inhibitor-based ART. VF was associated with any LLV before or after the switch and prior exposure to raltegravir, but not the level or frequency of LLV. CONCLUSION: The risks of LLV and VF were low in PLWH who had achieved virologic suppression and switched to EVG/c/FTC/TAF, and the presence of LLV and prior exposure to raltegravir increased the risk of VF.

YAP maintains the production of intermediate progenitor cells and upper-layer projection neurons in the mouse cerebral cortex.

BACKGROUND: The Hippo pathway is conserved through evolution and plays critical roles in development, tissue homeostasis and tumorigenesis. Yes-associated protein (YAP) is a transcriptional coactivator downstream of the Hippo pathway. Previous studies have demonstrated that activation of YAP promotes proliferation in the developing brain. Whether YAP is required for the production of neural progenitor cells or neurons in vivo remains unclear. RESULTS: We demonstrated that SATB homeobox 2 (SATB2)-positive projection neurons (PNs) in upper layers, but not T-box brain transcription factor 1-positive and Coup-TF interacting protein 2-positive PNs in deep layers, were decreased in the neonatal cerebral cortex of Yap conditional knockout (cKO) mice driven by Nestin-Cre. Cell proliferation was reduced in the developing cerebral cortex of Yap-cKO. SATB2-positive PNs are largely generated from intermediate progenitor cells (IPCs), which are derived from radial glial cells (RGCs) during cortical development. Among these progenitor cells, IPCs but not RGCs were decreased in Yap-cKO. We further demonstrated that cell cycle re-entry was reduced in progenitor cells of Yap-cKO, suggesting that fewer IPCs were generated in Yap-cKO. CONCLUSION: YAP is required for the production of IPCs and upper-layer SATB2-positive PNs during development of the cerebral cortex in mice.