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Abstract Conversational artificial intelligence (AI), particularly AI-based conversational agents (CAs), is gaining traction in mental health care. Despite their growing usage, there is a scarcity of comprehensive evaluations of their impact on mental health and well-being. This systematic review and meta-analysis aims to fill this gap by synthesizing evidence on the effectiveness of AI-based CAs in improving mental health and factors influencing their effectiveness and user experience. Twelve databases were searched for experimental studies of AI-based CAs’ effects on mental illnesses and psychological well-being published before May 26, 2023. Out of 7834 records, 35 eligible studies were identified for systematic review, out of which 15 randomized controlled trials were included for meta-analysis. The meta-analysis revealed that AI-based CAs significantly reduce symptoms of depression (Hedge’s g 0.64 [95% CI 0.17–1.12]) and distress (Hedge’s g 0.7 [95% CI 0.18–1.22]). These effects were more pronounced in CAs that are multimodal, generative AI-based, integrated with mobile/instant messaging apps, and targeting clinical/subclinical and elderly populations. However, CA-based interventions showed no significant improvement in overall psychological well-being (Hedge’s g 0.32 [95% CI –0.13 to 0.78]). User experience with AI-based CAs was largely shaped by the quality of human-AI therapeutic relationships, content engagement, and effective communication. These findings underscore the potential of AI-based CAs in addressing mental health issues. Future research should investigate the underlying mechanisms of their effectiveness, assess long-term effects across various mental health outcomes, and evaluate the safe integration of large language models (LLMs) in mental health care.

ABSTRACT: Diabetes has become a global concern at present, among which type 2 diabetes mellitus (T2DM) accounts for approximately 90 %–95 % of patients. T2DM is a type of metabolic disorder syndrome that results from a genetic defect, and it is based on insulin resistance and an insulin secretion disorder. The occurrence of T2DM is usually the outcome of both genetic and environmental factors and their interactions. The etiology and pathogenesis of diabetes have not been fully elucidated, and no radical therapeutic cure has been found. Patients with T2DM suffer from complications such as the development of a chronic hyperglycemic condition and even serious metabolic disorders and organ damage in the body and depression and dementia, in addition to other chronic complications. Many studies have suggested that diet is crucial in the development of diabetes and the control of blood glucose. Natural substances have the characteristics of low toxicity and few side effects and may be key to the development of diabetic health products and preventive treatments. This paper reviews the etiology, pathogenesis, risks, treatments and diets related to T2DM to summarize the types of recently available natural products, from both local and foreign sources, for lowering blood glucose at home and their application in supplementary hypoglycemic foods. The key findings and conclusions suggest that there are various known T2DM-inducing factors, including genetic and environmental factors and three types of hybrid factors.

Background/purpose: Limited data are available on the role of illicit non-injecting drug use in a prolonged HIV outbreak that predominantly affected men who have sex with men (MSM) in Taiwan since 2006. We aimed to assess associations between specific types of drug use and incident HIV infections in this outbreak. Methods: We conducted a retrospective case–control study among MSM clients at voluntary counselling and testing (VCT) service at National Taiwan University Hospital (Taipei, Taiwan). We used BED IgG-capture enzyme immunoassay to identify incident HIV infection (cases), individually matched to HIV-negative MSM clients (controls) by HIV testing date. We used a structured questionnaire to obtain the information on illicit drug use and sexual risk behaviors. Results: From a total of 15,305 MSM client visits during 2006–2015, 387 cases were matched to 1012 controls. Use of inhaled nitrites (adjusted odds ratio [aOR] 2.1), MDMA (aOR 2.9), amphetamines (aOR 1.6), and ketamine (aOR 1.5) were independently associated with incident HIV infection. Polydrug (≥2 drugs) use was associated with the highest risk (aOR 4.3; 95% CI 2.6–7.2). While the proportion of MSM VCT clients who reported use of any recreational drug remained stable during 2006–2015 (average: 9.7%, P: 0.38), there was a shift in specific types of drug use, from MDMA/ketamine to inhaled nitrites/amphetamine, after 2011 (all Ps

BackgroundHealth care and well-being are 2 main interconnected application areas of conversational agents (CAs). There is a significant increase in research, development, and commercial implementations in this area. In parallel to the increasing interest, new challenges in designing and evaluating CAs have emerged. ObjectiveThis study aims to identify key design, development, and evaluation challenges of CAs in health care and well-being research. The focus is on the very recent projects with their emerging challenges. MethodsA review study was conducted with 17 invited studies, most of which were presented at the ACM (Association for Computing Machinery) CHI 2020 conference workshop on CAs for health and well-being. Eligibility criteria required the studies to involve a CA applied to a health or well-being project (ongoing or recently finished). The participating studies were asked to report on their projects’ design and evaluation challenges. We used thematic analysis to review the studies. ResultsThe findings include a range of topics from primary care to caring for older adults to health coaching. We identified 4 major themes: (1) Domain Information and Integration, (2) User-System Interaction and Partnership, (3) Evaluation, and (4) Conversational Competence. ConclusionsCAs proved their worth during the pandemic as health screening tools, and are expected to stay to further support various health care domains, especially personal health care. Growth in investment in CAs also shows the value as a personal assistant. Our study shows that while some challenges are shared with other CA application areas, safety and privacy remain the major challenges in the health care and well-being domains. An increased level of collaboration across different institutions and entities may be a promising direction to address some of the major challenges that otherwise would be too complex to be addressed by the projects with their limited scope and budget.

BackgroundPreoperative two-dimensional manual measurement of pulmonary artery diameter in a single-cut axial view computed tomography (CT) image is a commonly used non-invasive prediction method for pulmonary hypertension. However, the accuracy may be unreliable. Thus, this study aimed to evaluate the correlation of short-term surgical outcomes and pulmonary artery/aorta (PA/Ao) diameter ratio measured by automated three-dimensional (3D) segmentation in lung cancer patients who underwent thoracoscopic lobectomy.Materials and methodsWe included 383 consecutive lung cancer patients with thin-slice CT images who underwent lobectomy at a single institute between January 1, 2011 and December 31, 2019. Automated 3D segmentation models were used for 3D vascular reconstruction and measurement of the average diameters of Ao and PA. Propensity-score matching incorporating age, Charlson comorbidity index, and lobectomy performed by uniportal VATS was used to compare clinical outcomes in patients with PA/Ao ratio ≥1 and those 3 cm (p = 0.002) both significantly predict the incidence of postoperative complications.ConclusionsPulmonary artery/aorta diameter ratio ≥ 1 measured by automated 3D segmentation may predict postoperative complications in lung cancer patients who underwent lobectomy.

Background: Cataract surgery in combination with or after trabeculectomy is often required for improving vision in glaucoma patients. Intraocular pressure (IOP) changes may influence refractive outcomes after cataract surgery. We compared refractive outcomes of the combined and sequential approaches in managing glaucoma and cataract. Methods: This retrospective case–control study included 52 patients (57 eyes) who underwent phacotrabeculectomy (combined group) and 39 patients (42 eyes) who underwent phacoemulsification at least three months post-trabeculectomy (sequential group). The IOP and refraction prediction error were compared at three months after cataract surgery. Univariate regression analyses were used to assess risk factors for the postoperative refraction prediction error. Results: Anti-glaucomatous medications were not administered to either group. The mean postoperative IOP (12.96 vs. 13.80 mmHg; P = .392), refraction prediction error (−0.32 ± 1.53 vs. −0.47 ± 1.14 D, P = .594), mean absolute error (1.02 ± 1.18 vs. 0.8 ± 0.93 D, P = .320), and surgically induced astigmatism (1.85 ± 1.40 vs. 2.16 ± 1.16 D, P = .161) did not differ significantly between the combined and sequential groups. In the sequential group, the refraction prediction error correlated to the IOP change, with a 1-mm Hg rise resulting in a −0.07-diopter shift between the expected and observed refraction (r = −0.380, R2 = 0.144, P = .013); no such correlation was observed in the combined group. Conclusion: Both approaches resulted in similar effective IOP control and accurate intraocular lens predictability. The IOP change affected the postoperative refraction prediction error only in the sequential approach.

Diagnosis of the Human Immunodeficiency Virus (HIV) remains challenging due to non-specific clinical presentations and mostly flu-like symptoms, e.g., fever, headache, sore throat, and general weakness. Oral lesions, such as oral candidiasis and Kaposi sarcoma, are also frequently associated with HIV infection, whereas laryngeal manifestations are rare. We report two cases of newly diagnosed HIV patients with clinical presentations of sore throat, and endoscopy revealed an epiglottic ulcerative tumor-like lesion. A laryngomicrosurgical biopsy of the lesions was performed for persistent symptoms and suspicion of malignancy. The result revealed acute and chronic inflammation without a conclusive pathology diagnosis. Further laboratory analysis was arranged in consideration of autoimmune diseases, Epstein–Barr virus (EBV), and HIV infection due to their persistent and atypical symptoms. The results were positive for HIV infection. These patients were treated successfully with antiviral treatment and the laryngeal symptoms improved within weeks. In patients with idiopathic and persistent epiglottitis or an epiglottic ulcer after medical treatment, HIV infection needs to be considered as a potential etiology in order to institute proper treatment.

Background: Many patients with obstructive sleep apnea (OSA) are mouth-breathers. Mouth-breathing not only narrows the upper airway, consequently worsening the severity of OSA, but also it affects compliance with nasal continuous positive airway pressure (CPAP) treatment. This study aimed to investigate changes in OSA by the use of mouth tape in mouth-breathers with mild OSA. Method: Mouth-breathers with mild OSA who met inclusion criteria and tolerated the sealing of the mouth were enrolled in the study. We used 3M silicone hypoallergenic tape was used to seal the mouths of the participants during sleep. The home sleep test (HST) used in this study was ApneaLink®. Subjects received both a baseline HST and an outcome HST to be used 1 week later while their mouths were taped. The changes between the baseline and the outcome HSTs were compared, and the factors that influenced the differences in the sleep-test parameters after the shift of the breathing route were analyzed. A “responder” was defined as a patient who experienced a reduction from the baseline snoring index of at least 50% under mouth-taping in the HST; otherwise, patients were considered as having a poor response. Results: A total of 20 patients with mild OSA were included. Following the taping of the mouth, a good response was found in 13 patients (65%). The median apnea/hypopnea index (AHI) decreased significantly, from 8.3 to 4.7 event/h (by 47%, p = 0.0002), especially in supine AHI (9.4 vs. 5.5 event/h, p = 0.0001). The median snoring index (SI) was also improved (by 47%, 303.8 vs. 121.1 event/h, p = 0.0002). Despite no significant difference in the mean saturation, improvements in the oxygen desaturation index (8.7 vs. 5.8, p = 0.0003) and the lowest saturation (82.5% vs. 87%, p = 0.049) were noted. The change in AHI was associated with baseline AHI (r = −0.52, p = 0.02), oxygen desaturation index (ODI) (r = −0.54, p = 0.01), and SI (r = −0.47, p = 0.04). The change in SI was strongly associated with baseline SI (r = −0.77, p = 0.001). Conclusions: Mouth-taping during sleep improved snoring and the severity of sleep apnea in mouth-breathers with mild OSA, with AHI and SI being reduced by about half. The higher the level of baseline AHI and SI, the greater the improvement was shown after mouth-taping. Mouth-taping could be an alternative treatment in patients with mild OSA before turning to CPAP therapy or surgical intervention.

The quantitative analysis of cell surface antigens has attracted increasing attention due to the antigenic variation recognition that can facilitate early diagnoses. This paper presents a novel methodology based on the optical “cell-tearing” and the especially proposed “dilution regulations” to detect variations in cell surface antigens. The cell attaches to the corresponding antibody-coated slide surface. Then, the cell-binding firmness between a single cell and the functionalized surface is assayed by optically tearing using gradually reduced laser powers incorporated with serial antibody dilutions. Groups B and B3 of red blood cells (RBCs) were selected as the experiment subject. The results indicate that a higher dilution called for lower power to tear off the cell binding. According to the proposed relative-quantitative analysis theory, antigenic variation can be intuitively estimated by comparing the maximum allowable dilution folds. The estimation result shows good consistency with the finding in the literature. This study suggests a novel methodology for examining the variation in cell surface antigens, expected to be widely capable with potential sensor applications not only in biochemistry and biophysics, but also in the micro-/nano- engineering field.

Errors occurred in the standard deviation of the Dice similarity coefficient (DSC) described in the original publication [...]

Pulmonary hypertension should be preoperatively evaluated for optimal surgical planning to reduce surgical risk in lung cancer patients. Preoperative measurement of vascular diameter in computed tomography (CT) images is a noninvasive prediction method for pulmonary hypertension. However, the current estimation method, 2D manual arterial diameter measurement, may yield inaccurate results owing to low tissue contrast in non-contrast-enhanced CT (NECT). Furthermore, it provides an incomplete evaluation by measuring only the diameter of the arteries rather than the volume. To provide a more complete and accurate estimation, this study proposed a novel two-stage deep learning (DL) model for 3D aortic and pulmonary artery segmentation in NECT. In the first stage, a DL model was constructed to enhance the contrast of NECT; in the second stage, two DL models then applied the enhanced images for aorta and pulmonary artery segmentation. Overall, 179 patients were divided into contrast enhancement model (n = 59), segmentation model (n = 120), and testing (n = 20) groups. The performance of the proposed model was evaluated using Dice similarity coefficient (DSC). The proposed model could achieve 0.97 ± 0.007 and 0.93 ± 0.002 DSC for aortic and pulmonary artery segmentation, respectively. The proposed model may provide 3D diameter information of the arteries before surgery, facilitating the estimation of pulmonary hypertension and supporting preoperative surgical method selection based on the predicted surgical risks.

Myocardial infarction is the leading cause of morbidity and mortality worldwide. Although myocardial reperfusion after ischemia (I/R) is an effective method to save ischemic myocardium, it can cause adverse reactions, including increased oxidative stress and cardiomyocyte apoptosis. Mitochondrial fission and mitophagy are essential factors for mitochondrial quality control, but whether they play key roles in cardiac I/R injury remains unknown. New pharmacological or molecular interventions to alleviate reperfusion injury are currently considered desirable therapies. Vitamin D3 (Vit D3) regulates cardiovascular function, but its physiological role in I/R-exposed hearts, especially its effects on mitochondrial homeostasis, remains unclear. An in vitro hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate myocardial I/R injury. H/R treatment significantly reduced H9c2 cell viability, increased apoptosis, and activated caspase 3. In addition, H/R treatment increased mitochondrial fission, as manifested by increased expression of phosphorylated dynein-related protein 1 (p-Drp1) and mitochondrial fission factor (Mff) as well as increased mitochondrial translocation of Drp1. Treatment with the mitochondrial reactive oxygen species scavenger MitoTEMPO increased cell viability and decreased mitochondrial fission. H/R conditions elicited excessive mitophagy, as indicated by increased expression of BCL2-interacting protein 3 (BNIP3) and light chain (LC3BII/I) and increased formation of autolysosomes. In contrast, Vit D3 reversed these effects. In a mouse model of I/R, apoptosis, mitochondrial fission, and mitophagy were induced. Vit D3 treatment mitigated apoptosis, mitochondrial fission, mitophagy, and myocardial ultrastructural abnormalities. The results indicate that Vit D3 exerts cardioprotective effects against I/R cardiac injury by protecting mitochondrial structural and functional integrity and reducing mitophagy.

Background/Purpose: To obtain current epidemiological data for better vaccination policies, this study aimed to assess the incidence and risk factors of herpes zoster in human immunodeficiency virus (HIV)-positive patients initiating combination antiretroviral therapy (cART) in Taiwan. Methods: Between June, 2012 and May, 2015, we prospectively identified zoster cases in HIV-positive patients initiating cART. Clinical information was collected on demographics, prior zoster, plasma HIV-1 RNA load (PVL), and CD4 count at baseline and during follow up. A case–control study by 1:2 matched pairs was used to identify the risk factors for zoster development. Results: During the 3-year study period, 826 patients with a mean age of 32.9 years were included, and 7.7% had prior zoster. The mean baseline CD4 count and PVL were 286 cells/μL and 4.90 log10 copies/mL, respectively. Fifty-four (6.5%) patients developed zoster after initiation of cART, with 43 episodes (79.6%) occurring within 1 year of cART initiation, which corresponded to an overall incidence rate of 3.61/100 person-years. The multivariate analysis revealed that prior zoster (adjusted odds ratio = 3.143; 95% confidence interval, 1.385–7.133) and baseline CD4 count 5 log10 copies/mL were risk factors for zoster development after cART initiation in multivariate analysis. Conclusions: Herpes zoster occurred in 6.5% of HIV-positive Taiwanese patients after initiation of cART, which was associated with prior zoster and baseline CD4 count < 200 cells/μL or baseline PVL > 5 log10 copies/mL.

Background: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified. Methods: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed. Results: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8–27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) (p = 0.026) than in the HHA group (7.5%). Conclusions: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP.

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. It is mainly used in epilepsy and Alzheimer’s disease. However, the effects of the ketogenic diet on liver fibrosis remains unknown. Through ketogenic diet consumption, β-hydroxybutyrate (bHB) and acetoacetate (AcAc) are two ketone bodies that are mainly produced in the liver. It is reported that bHB and AcAc treatment decreases cancer cell proliferation and promotes apoptosis. However, the influence of bHB and AcAc in hepatic stellate cell (HSC) activation and liver fibrosis are still unclear. Therefore, this study aimed to investigate the effect of the ketogenic diet and ketone bodies in affecting liver fibrosis progression. Our study revealed that feeding a high-fat ketogenic diet increased cholesterol accumulation in the liver, which further enhanced the carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis. In addition, more severe liver inflammation and the loss of hepatic antioxidant and detoxification ability were also found in ketogenic diet-fed fibrotic mouse groups. However, the treatment with ketone bodies (bHB and AcAc) did not suppress transforming growth factor-β (TGF-β)-induced HSC activation, platelet-derived growth factor (PDGF)-BB-triggered proliferation, and the severity of CCl4-induced liver fibrosis in mice. In conclusion, our study demonstrated that feeding a high-fat ketogenic diet may trigger severe steatohepatitis and thereby promote liver fibrosis progression. Since a different ketogenic diet composition may exert different metabolic effects, more evidence is necessary to clarify the effects of a ketogenic diet on disease treatment.

Our goal was to investigate the changes in artificial short-linear chromosome average copy numbers per cell arising from partial or full loss of Mitotic Arrest-Deficient 2 (MAD2) spindle checkpoint function in budding yeast Saccharomyces cerevisiae. Average artificial linear chromosome copy numbers in a population of cells, as measured by quantitative polymerase chain reactions (qPCR), and retention rates, as measured by fluctuation analyses, were performed on a total of 62 individual wild type and mad2∆ mutant haploid and diploid clones. Wild type cells, both haploids and diploids, displayed phenotypically unique clone-to-clone differences: one group of 15 clones displayed low-copy numbers per cell and high retention rates, were 1 clone was found to have undergone a genomic integration event, and the second group of 15 clones displayed high copy numbers per cell and low retention rates, with the latter values being consistent with the previously published results where only a single clone had been measured. These chromosome states were observed to be unstable when propagated for 10 days under selection, where high copy-low retention rate clones evolved into low copy-high retention rate clones, but no evidence for integration events was observed. By contrast, mad2∆ haploid and mad2∆/mad2∆ diploids displayed a suppression of the clone-to-clone differences, where 20 out of 21 clones had mid-level artificial linear chromosome copy numbers per cell, but maintained elevated chromosome retention rates. The elevated levels in retention rates in mad2∆ and mad2∆/mad2∆ cells were also maintained even in the absence of selection during growth over 3 days. MAD2/mad2∆ heterozygous diploids displayed multiple clonal groups: 4 with low copy numbers, 5 with mid-level copy numbers, and 1 with a high copy number of artificial linear chromosomes, but all 10 clones uniformly displayed low retention rates. Our observations reveal that MAD2 function contributes to the ability of yeast cells to maintain a high number of artificial linear chromosomes per cell in some clones, but, counter-intuitively, mad2∆ suppresses clone-to-clone differences and leads to an improvement in artificial linear chromosome retention rates yielding a more uniform and stable clonal population with mid-level chromosome copy numbers per cell.

Substantial developments have been established in the past few years for enhancing the performance of brain–computer interface (BCI) based on steady-state visual evoked potential (SSVEP). The past SSVEP-BCI studies utilized different target frequencies with flashing stimuli in many different applications. However, it is not easy to recognize user’s mental state changes when performing the SSVEP-BCI task. What we could observe was the increasing EEG power of the target frequency from the user’s visual area. BCI user’s cognitive state changes, especially in mental focus state or lost-in-thought state, will affect the BCI performance in sustained usage of SSVEP. Therefore, how to differentiate BCI users’ physiological state through exploring their neural activities changes while performing SSVEP is a key technology for enhancing the BCI performance. In this study, we designed a new BCI experiment which combined working memory task into the flashing targets of SSVEP task using 12 Hz or 30 Hz frequencies. Through exploring the EEG activity changes corresponding to the working memory and SSVEP task performance, we can recognize if the user’s cognitive state is in mental focus or lost-in-thought. Experiment results show that the delta (1–4 Hz), theta (4–7 Hz), and beta (13–30 Hz) EEG activities increased more in mental focus than in lost-in-thought state at the frontal lobe. In addition, the powers of the delta (1–4 Hz), alpha (8–12 Hz), and beta (13–30 Hz) bands increased more in mental focus in comparison with the lost-in-thought state at the occipital lobe. In addition, the average classification performance across subjects for the KNN and the Bayesian network classifiers were observed as 77% to 80%. These results show how mental state changes affect the performance of BCI users. In this work, we developed a new scenario to recognize the user’s cognitive state during performing BCI tasks. These findings can be used as the novel neural markers in future BCI developments.

OBJECTIVES:Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS:Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events. RESULTS:During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity. CONCLUSIONS:The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

Nevirapine extended-release (NVP-XR) taken once daily remains an effective antiretroviral agent for patients infected with HIV-1 strains that do not harbor resistance mutations. Presence of tablet remnants of NVP XR in stools was reported in 1.19% and 3.05% of subjects in two clinical trials. However, the prevalence may have been underestimated because the information was retrospectively collected in the studies.Between April and December 2014, we prospectively inquired about the frequency of noticing tablet remnants of NVP XR in stools in HIV-1-infected patients who switched to antiretroviral regimens containing NVP XR plus 2 nucleos(t)ide reverse-transcriptase inhibitors. Patients were invited to participate in therapeutic drug monitoring of plasma concentrations of NVP 12 or 24 hours after taking the previous dose (C12 and C24, respectively) of NVP XR using high-performance liquid chromatography. The information on clinical characteristics, including plasma HIV RNA load and CD4 lymphocyte count, at baseline and during follow-up was recorded.During the 9-month study period, 272 patients switched to NVP XR-based regimens and 60 (22.1%) noticed tablet remnants of NVP XR in stools, in whom 54.2% reported noticing the tablet remnants at least once weekly. Compared with patients who did not notice tablet remnants, those who noticed tablet remnants had a higher mean CD4 lymphocyte count (629 vs 495 cells/mm3, P = 0.0002) and a similar mean plasma HIV RNA load (1.57 vs 1.61 log10 copies/mL, P = 0.76) on switch. At about 12 and 24 weeks after switch, patients who noticed tablet remnants continued to have a similar mean plasma HIV RNA load (1.39 vs 1.43 log10 copies/mL, P = 0.43; and 1.30 vs 1.37 log10 copies/mL, P = 0.26, respectively), but had a lower median NVP C12 (3640 vs 4730 ng/mL, P = 0.06), and a similar median NVP C24 (3220 vs 3330 ng/ml, P = 0.95) when compared with those who did not notice tablet remnants.The presence of tablet remnants of NVP XR in stools is not uncommon in HIV-1-infected Taiwanese patients receiving NVP XR-based antiretroviral regimens, which does not have an adverse impact on the virological and immunological outcomes.