A Rare Autochthonous Case of Hepatic Hydatid Cyst in the Non-Endemic Region of Taiwan.

BACKGROUND Hepatic hydatid cyst disease, caused by the parasite Echinococcus granulosus, is endemic in certain rural areas of the world, but not in most of East Asia outside Mainland China. In Taiwan, only one autochthonous case has been reported over the past 40 years. We present the case of an urban 91-year-old female patient without international travel history for more than 40 years. CASE REPORT The 91-year-old woman who used a wheelchair came to the Emergency Department reporting melena for 2 days and 1 episode of coffee-grounds vomitus. Epigastric tenderness was present. An incidental finding of elevated liver enzymes along with the clinical picture prompted further survey. Computed tomography revealed a 14×10×12 cm homogeneous cystic lesion in the right hepatic lobe with a partially calcified wall. On sonograms, a similar lesion was found, and the pathognomic "water-lily" sign was visualized along with the isoechoic-to-hypoechoic internal septa, fulfilling the diagnosis despite the patient's refusal to undergo magnetic resonance imaging studies and invasive definite diagnostic procedures. Although anthelmintic chemotherapy and invasive therapeutic measures were also refused, her symptoms improved and was not recurrent under supportive measures. However, the cyst was still present 12 months after discharge. CONCLUSIONS The case highlights that in areas with few cases of hepatic hydatid disease, the accurate diagnosis could be missed in patients without a significant epidemiological history. However, once imaging findings, especially those that are pathognomic, are appropriately interpreted on at least 2 imaging modalities, such cases could be diagnosed without further definitive studies.

Participation in cancer screening among people living with HIV at a university hospital.

Between March and October, 2018, 1248 people living with HIV completed questionnaire interviews for cancer screening, of whom 46.9% (n = 585) completed free-of-charge cancer screening. Time constraint (50.1%) was the most common reason provided for refusal to participate in cancer screening. None of the participants were diagnosed with any of the four cancers.

Controllable growth of carbon nanosheets in the montmorillonite interlayers for high-rate and stable anode in lithium ion battery.

A novel insertable and pseudocapacitive Li+ ion material for highly ordered layered montmorillonite/carbon is explored in the present study. The commercially available protonated montmorillonite and 3,3'-diaminobenzidine act as starting materials to synthesize the layered material via hydrothermal intercalation, oxidative polymerization and carbonization. This method of preparing montmorillonite/carbon nanocomposite exhibits several advantages. To be specific, raw materials are low cost and naturally abundant; the montmorillonite can undergo proton exchange easily to form a permutable proton-type material, and the protons in the layered nanocomposite can be directly substituted by the polymerizable molecules (e.g., 3,3'-diaminobenzidine). Accordingly, a sheet-like montmorillonite/carbon layered nanocomposite is achieved with the carbon stacking on the montmorillonite substrate for the intercalation behavior. As revealed from the electrochemical results, montmorillonite/carbon nanocomposite can deliver a high reversible capacity of 1432 mA h g-1 at 50 mA g-1 and superior rate capacity of 920 mA h g-1 at 10 000 mA g-1 for the lithium ion battery. Furthermore, the full cell with LiFePO4 as cathode and montmorillonite/carbon as anode maintains 94% capacity retention over 50 cycles as well as high coulombic efficiency.

Impact of initiation of combination antiretroviral therapy according to the WHO recommendations on the survival of HIV-positive patients in Taiwan.

BACKGROUND/PURPOSE: Early initiation of antiretroviral therapy (ART) reduces the risks for serious infections and mortality. We aimed to assess the outcomes of initiating ART among HIV-positive Taiwanese according to the CD4 cut-off values by the WHO recommendations. METHODS: We reviewed medical records of patients with newly diagnosed HIV infection between 2004 and 2015 and 3 groups of patients were defined according to the timing of ART initiation based on CD4 count recommended by WHO: Group 1 between 2004 and 2009; Group 2 between 2010 and 2012; and Group 3 between 2013 and 2015. The primary outcome was all-cause mortality. All patients were followed until 2 years after the last patient was included in each group. RESULTS: Of 2022 patients included, the mortality rate was 18.28, 14.01, and 9.10 deaths per 1000 person-years of follow-up (PYFU) in Groups 1, 2, and 3, respectively. In multivariable Cox regression analysis, factors associated with mortality were age (per 1-year increase, adjusted hazard ratio [AHR], 1.06; 95% CI, 1.05-1.08), presence of AIDS-defining disease at HIV diagnosis (AHR, 4.81; 95% CI, 2.99-7.74), solid-organ malignancy (AHR, 3.10; 95% CI, 1.86-5.18), and initiation of ART (AHR, 0.09; 95% CI, 0.05-0.16). By competing risk regression model for non-AIDS-related death, the AHR for Group 3 versus Group 1 was 0.27 (95% CI, 0.09-0.80). CONCLUSIONS: While continued efforts are needed to improve early diagnosis and linkage to care, initiation of cART improved survival among HIV-positive patients in Taiwan according to the increasing CD4 cut-off values that were recommended by the WHO.

Estimated risk of cardiovascular disease among the HIV-positive patients aged 40 years or older in Taiwan.

BACKGROUND: Cardiovascular disease (CVD) is an emerging cause of morbidity and mortality among HIV-positive patients receiving successful combination antiretroviral therapy, but their CVD risk has been rarely investigated in Asia-Pacific region. We aimed to assess the CVD risk of HIV-positive Taiwanese outpatients. METHODS: We did cross-sectional questionnaire interviews to collect information of HIV-positive Taiwanese patients aged 40-79 at the HIV clinics of a medical center from 1 March to 31 August, 2017. The Framingham Risk Score (FRS), Atherosclerotic Cardiovascular Disease (ASCVD) risk score and Data-Collection on Adverse effects of Anti-HIV Drugs (D:A:D) risk score were used to estimate their CVD risk. RESULTS: Of the screened 1251 patients, 1006 (80.4%) with complete data to assess their CVD risk were included for analyses. The prevalence of patients aged 40-75 and with a high CVD risk was 30.6% by FRS, 3.7% by D:A:D (R) risk score, and 22.2% by ASCVD risk score. In multiple logistic regression, older age, current smoking, higher systolic blood pressure, and higher triglyceride and fasting glucose levels were independently associated with the ASCVD risk score ≥7.5%. If current smokers aged 55-59 had stopped smoking, the proportions of them with a 10-year CVD risk of ≥10% by FRS and ≥7.5% by ASCVD risk score would have decreased by 35.3% and 20.0%, respectively. CONCLUSIONS: Higher CVD risk estimates among HIV-positive Taiwanese aged 40-75 were associated with an older age, current smoking, higher systolic blood pressure, hypertriglyceridemia, and hyperglycemia. Smoking cessation could potentially lead to significant decreases of CVD risk.

Male Patients with Longstanding Type 2 Diabetes Have a Higher Incidence of Hypoglycemia Compared with Female Patients.

INTRODUCTION: To explore whether there was a gender difference in the risk of hypoglycemia during intensive insulin therapy in patients with longstanding type 2 diabetes (T2D). This was a post hoc analysis of a single-center, open-label and prospective trial. METHODS: All subjects were admitted as inpatients, underwent a standard bread meal test at baseline and received a 7-day continuous subcutaneous insulin infusion (CSII) therapy for achieving glycemic control. Patients then were randomized 1:1 to two groups receiving (1) 4 days of Novo Mix 30 followed by 2 days of Humalog Mix 50; (2) 4 days of Humalog Mix 50 followed by 2 days of Novo Mix 30. All patients were subjected to 4-day retrospective continuous glucose monitoring (CGM) during the last 4 days in this study. The primary outcome was the incidences of hypoglycemia monitored by CGM at the end point. RESULTS: A total of 102 patients met the inclusion criteria and completed the study. Our data revealed that 29 patients (28%) experienced hypoglycemia as detected by CGM at the end point. Binary logistic stepwise regression analysis showed that only gender significantly correlated with hypoglycemia (B = 1.17, p = 0.017). Importantly, male patients had a significantly higher incidence of hypoglycemia than female patients (male = 20/52, female = 9/50, p = 0.022), although male patients required significantly lower insulin doses to maintain glycemic control than female patient (p = 0.00). CONCLUSION: Male patients with longstanding T2D had a higher incidence of hypoglycemia than female patients during intensive insulin therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR-IPR-15007340.

Comparison of Efficacy and Safety of Lispro and Aspart Evaluated by Continuous Glucose Monitoring System in Patients with Newly Diagnosed Type 2 Diabetes.

OBJECTIVE: To compare the effect of the rapid-acting insulin analogues (RAIAs) aspart (NovoRapid) and lispro (Prandilin) on glycemic variations by continuous glucose monitoring system (CGMS) in patients within newly diagnosed type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) and metformin intensive therapy. METHODS: This is a single-blind randomized controlled trial. A total of 110 patients with newly diagnosed T2DM and with hemoglobin A1c (HbA1c%) above 9% was hospitalized and randomly divided into two groups: group Asp (NovoRapid group) and group Lis (Prandilin group). They all received CSII and metformin therapy. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. C-peptide and insulin and fructosamine were determined. CGMS was continuously applied for 4 days after reaching the glycemic target. RESULTS: There were no significant differences in daily dosages of insulin, fasting plasma C-P and 2 h postprandial C-P and insulin, and fructosamine at the baseline and endpoint between the groups Asp and Lis. No significant differences were seen in the 24 h mean amplitude of glycemic excursions (MAGE), 24 h mean blood glucose (MBG), the standard deviation of the MBG (SDBG), fasting blood glucose, number of glycemic excursion (NGE), and the incidence of hypoglycemia between the two groups. Similarly, no significant differences were found in areas under the curve (AUC) of glucose above 10.0 mmol/L or the decremental area over the curve (AOC) of glucose below 3.9 mmol/L between the two groups. CONCLUSIONS: Lispro and aspart had the similar ability to control the glycemic variations in patients with newly diagnosed T2DM. This study was registered with ClinicalTrials.gov, number ChiCTR-IPR-17010338.

Management of glycemic variation in diabetic patients receiving parenteral nutrition by continuous subcutaneous insulin infusion (CSII) therapy.

To compare the continuous subcutaneous insulin infusion (CSII) or insulin glargine based multiple injections (MDI) therapy on glycemic variations in diabetic patients receiving PN outside of intensive care settings. This was a single-center, randomized, open-label trial. Patients with type 2 diabetes (T2D) who were receiving parenteral nutrition (PN) were recruited. After baseline data were collected, recruited patients were then randomized 1:1 to a CSII group or a MDI group. All patients were subjected to a 4-day retrospective Continuous Glucose Monitoring (CGM). The primary endpoint was the differences of the 24-hrs mean amplitude of glycemic excursion (MAGE) in patients receiving the PN therapy between the two groups. A total of 102 patients with T2D receiving PN were recruited. Patients in the CSII group had a significantly decreased mean glucose level (MBG), the standard deviation of MG (SDBG), MAGE, and the coefficient of variation (CV%) compared to those in MDI group (all P < 0.01). Furthermore, we found that the patients who received a bolus insulin dose required maintaining euglycemic control was gradually decreased during the PN period in both groups at the endpoint. The administration of insulin via CSII led to a significant decrease in glycemic variations in patients receiving PN.

Young onset type 2 diabetic patients might be more sensitive to metformin compared to late onset type 2 diabetic patients.

It is unknown whether YOD (young onset diabetes) and LOD (late onset diabetes) require similar insulin doses for intensive insulin therapy with a metformin add-on to achieve glycemic control. We analyzed data from our two previously performed randomized, controlled open-label trials. Patients were randomized to receive either continuous subcutaneous insulin infusion (CSII) therapy or CSII combined with metformin therapy for 4 weeks. The studies concentrated on the differences in the insulin doses used for the two groups. We included 36 YOD (age < 40 yrs) and 152 LOD (age > 40 yrs) patients. YOD patients who received metformin combined with CSII therapy required significantly lower insulin doses to maintain euglycemic control compared to patients with LOD. A multivariate analysis, controlled for gender and the fasting blood concentration, was performed to determine the significance of the differences between groups, particularly with respect to the total and basal insulin doses. There was a trend toward improvement in ß-cell function and insulin resistance in terms of ΔHOMA-B and ΔHOMA-IR in patients with YOD compared to those with LOD. Newly diagnosed T2D patients with YOD required significantly lower insulin doses, particularly basal insulin doses, to maintain glycemic control compared to the LOD patients.

Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

INTRODUCTION: To investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy. METHODS: This was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study. RESULTS: A total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000-0600). A severe hypoglycemic episode was not observed in either group. CONCLUSION: Vildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan.

Antiretroviral therapy containing an integrase strand transfer inhibitor (INSTI) plus two NRTIs has become the recommended treatment for antiretroviral-naive HIV-1-infected patients in the updated guidelines. We aimed to determine the prevalence of INSTI-related mutations in Taiwan. Genotypic resistance assays were performed on plasma from ARV-naïve patients (N = 948), ARV-experienced but INSTI-naive patients (N = 359), and raltegravir-experienced patients (N = 63) from 2006 to 2015. Major INSTI mutations were defined according to the IAS-USA list and other substitutions with a Stanford HIVdb score ≧ 10 to at least one INSTI were defined as minor mutations. Of 1307 HIV-1 samples from patients never exposed to INSTIs, the overall prevalence of major resistance mutations to INSTIs was 0.9% (n = 12), with an increase to 1.2% in 2013. Of these 12 sequences, 11 harboured Q148H/K/R, one Y143R, and none N155H. Of 30 sequences (47.6%) with INSTI-resistant mutations from raltegravir-experienced patients, 17 harboured Q148H/K/R, 8 N155H, and 6 Y143C/R. Other than these major mutations, the prevalence of minor mutations were 5.3% and 38.1%, respectively, in ARV-naive and raltegravir-experienced patients. The overall prevalence of INSTI mutations remains low in Taiwan. Surveillance of INSTI resistance is warranted due to circulation of polymorphisms contributing to INSTI resistance and expected increasing use of INSTIs.

Risk of recurrent nontyphoid Salmonella bacteremia in human immunodeficiency virus-infected patients with short-term secondary prophylaxis in the era of combination antiretroviral therapy.

BACKGROUND/PURPOSE: Nontyphoid Salmonella (NTS) bacteremia causes high mortality and recurrence rates in human immunodeficiency virus (HIV)-infected patients. This study aimed to investigate the risk of recurrent NTS bacteremia in the era of combination antiretroviral therapy (cART). METHODS: The medical records of consecutive HIV-infected patients with NTS bacteremia from January 2006 to June 2014 were reviewed. The patients were divided into two groups: patients who achieved a decline of plasma HIV RNA load by ≥ 2 log10 after 4 weeks of cART (good short-term virological response) and those who failed to achieve the goal (poor short-term virological response). Clinical information was collected on the demographics, immunological and virological responses, prophylactic antibiotics used, episodes of recurrent NTS bacteremia, and mortality. RESULTS: During the study period, 49 patients with 52 episodes of NTS bacteremia were included: 29 patients in the good virological response group, in which 16 received secondary prophylaxis; and 20 patients in the poor response group, in which 15 received secondary prophylaxis. There were no recurrent episodes of NTS bacteremia in the good-response group, whereas the incidence rate of recurrent NTS bacteremia was 5.21 per 100 person-years and 56.42 per 100 person-years of follow-up in patients receiving and not receiving prophylaxis, respectively, in the poor-response group. No patients died in the good-response group, whereas five patients (25%) in the poor-response group died. The resistance rate of 52 NTS isolates tested to ciprofloxacin was 7.7%. CONCLUSION: The risk of recurrent NTS bacteremia is low in HIV-infected patients who achieve short-term virological response to cART, regardless of secondary prophylaxis.

Presence of Tablet Remnants of Nevirapine Extended-Release in Stools and Its Impact on Virological Outcome in HIV-1-Infected Patients: A Prospective Cohort Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Detection of human parvovirus 4 viremia in the follow-up blood samples from seropositive individuals suggests the existence of persistent viral replication or reactivation of latent viral infection.

BACKGROUND: The transmission routes for human parvovirus 4 (PARV4) infections in areas with high seroprevalence are not known. In the work described here, persistent PARV4 viral replication was investigated by conducting a longitudinal study. METHODS: Ten healthcare workers each provided a blood sample at the beginning of the study (first sample) and 12 months later (second sample). The paired samples were tested for PARV4-positivity by immunoblotting analysis and nested polymerase chain reactions. RESULTS: IgG antibodies against PARV4 were detected in six participants, three of whom also had IgM antibodies against PARV4. The immunoblotting results did not vary over time. PARV4 DNA was detected in the first blood sample from one participant who had IgG antibodies against PARV4 and in the second blood samples from 2 participants who had IgG and IgM antibodies against PARV4. CONCLUSIONS: Detection of PARV4 DNA in the second blood samples from two seropositive participants suggests the existence of persistent PARV4 replication or reactivation of inactive virus in the tissues. The finding of persistent or intermittent PARV4 replication in individuals with past infections provides an important clue toward unraveling the non-parenteral transmission routes of PARV4 infection in areas where the virus is endemic.

Autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy.

BACKGROUND: Autoimmune diseases-related arthritis has been rarely reported in HIV-1-infected patients. We aimed to investigate the incidence and clinical manifestations of autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in Taiwan. METHODS: We retrospectively reviewed medical records of all HIV-infected patients who had a diagnosis of autoimmune arthritis between 1993 and 2013. Demographic characteristics, clinical manifestations, serial CD4 and CD8 lymphocyte counts and plasma HIV viral loads, HLA-B27 status, and treatment response to HIV and rheumatic diseases were recorded. RESULTS: During the 20-year study period, totally 26 HIV-infected patients with autoimmune arthritis (0.7%) were diagnosed among 3623 HIV-infected patients. There were 18 patients with ankylosing spondylitis (AS), six with rheumatoid arthritis (RA), one with psoriatic arthritis, and one with Sjögren's syndrome. HLA-B27 antigens were all detected positive of AS patients. Fifteen patients (57.7%) developed autoimmune arthritis after HAART was initiated. The median age and CD4(+) T lymphocyte counts at the diagnosis of autoimmune arthritis were 35 (20-62 years) and 406 (3-695 cells/µL), respectively. Three patients had typical presentations of Reiter's syndrome. Both AS and RA patients achieved a good virological response with undetectable plasma HIV RNA load 12 months after receiving HAART(85.71% vs. 80%, respectively, p = 0.999). The treatment response to antirheumatic medications were similar between AS patients and RA patients (77.8% vs. 50%, p = 0.3068), but seems to be better than that reported for the general population (30-40%). CONCLUSION: A low prevalence of autoimmune arthritis among HIV-infected patients in the era of HAART was similar to that of the general Taiwanese population. Clinical manifestations of HIV-infected patients were similar to those described in HIV-uninfected patients. However, the treatment response to antirheumatic agents was better in HIV-infected patients in our study.

Comorbidities among the HIV-infected patients aged 40 years or older in Taiwan.

BACKGROUND: With the widespread use of combination antiretroviral therapy (cART), life expectancy of HIV-infected patients has significantly prolonged. An increasing number of HIV-infected patients are aging and concurrent use of medications are not uncommon for management of metabolic complications and cardiovascular diseases related to aging and prolonged exposure to cART. METHODS: We reviewed medical records of all HIV-infected patients aged 40 years or older who had been followed at a university hospital for HIV care in Taiwan between January and December 2013. A standardized case record form was used to collect information on demographics and clinical characteristics, comorbidity, cART, and concurrent medications. RESULTS: During the study period, 610 patients aged 40 to 49 years (mean, 44.1) and 310 aged 50 years or older (mean, 58.8) sought HIV care at this hospital. Compared with patients aged 40 to 49 years, those aged 50 years or older were significantly more likely to be female (15.9% vs 3.8%); to have received cART (97.7% vs 94.8%) and a lower plasma HIV RNA load (1.6 vs 1.7 log10 copies/ml); and to have diabetes mellitus (18.4% vs 4.6%), hypertension (31.0% vs 10.8%), hyperlipidemia (29.4% vs 11.6%), coronary artery disease (6.8% vs 0.5%), and an estimated glomerular filtration rate <60 ml/min/1.73 m2 (11.5% vs 2.7%); and were significantly less likely to have syphilis. Other than HIV infection, patients aged 50 years or older were more likely to have been receiving two or more concurrent medications than those aged 40 to 49 years (22.9% vs 6.4%). CONCLUSIONS: Our findings show a significant proportion of the HIV-infected patients aged 50 years or older have multiple comorbidities that may increase the risk for cardiovascular and renal complications. Issues of poly-pharmacy among the HIV-infected patients who are aging should be addressed to ensure adherence and minimize drug-drug interactions.

Skin rash related to once-daily boosted darunavir-containing antiretroviral therapy in HIV-infected Taiwanese: incidence and associated factor.

OBJECTIVES: The study aimed to investigate the incidence of and associated factors with skin rashes among HIV-infected Taiwanese patients who received once-daily darunavir (DRV) boosted by ritonavir (RTV) (800/100 mg) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs). METHODS: We reviewed the medical records of HIV-infected patients who switched to once-daily DRV/RTV-containing regimens between January 2012 and November 2013. Patients who switched from 2 NRTIs plus non-NRTI (nNRTI) or other protease inhibitor (PI) to 2 NRTIs plus PIs other than DRV were chosen as comparators. RESULTS: During the study period, 238 patients who switched to once-daily DRV/RTV-containing regimens (Group A) and 178 patients who switched from 2 NRTIs plus nNRTI or other PI to 2 NRTIs plus PI other than DRV/RTV (Group B) were included. There were no differences between Groups A and B in most of the baseline characteristics. Compared with Group B in which 7 (3.9%) developed rashes after switch to PI other than DRV, 26 patients (10.9%) in Group A developed rashes after a median interval of 14 days of starting DRV/RTV-containing regimens (P = 0.009). In multivariate analysis, patients with a history of rashes related to the previous nNRTI-containing regimens before starting DRV/RTV-containing regimens were more likely to develop rashes with an adjusted odds ratio of 3.53 (95% confidence interval, 1.45-8.62). CONCLUSIONS: Once-daily regimens containing DRV/RTV is associated with a higher rate of adverse cutaneous reactions than other PI-containing regimens in HIV-infected Taiwanese, especially in those who have a history of rashes to nNRTI-containing regimens before switch to DRV/RTV-containing regimens.

Reduced bone mineral density among HIV-infected patients in Taiwan: prevalence and associated factors.

BACKGROUND: Reduced bone mineral density (BMD) is an emerging threat to the successful long-term management of human immunodeficiency virus (HIV) infection among patients with access to combination antiretroviral therapy (cART). Data on the prevalence and associated factors of reduced BMD in Asian populations remain scarce. METHODS: From March 2002 to April 2006, a cross-sectional survey was conducted among HIV-infected patients aged ≥ 20 years at the National Taiwan University Hospital. BMD of the lumbar spine was measured with the use of dual-energy X-ray absorptiometry. Osteopenia was defined as a BMD T-score between -1.0 and -2.5, and osteoporosis was defined as a BMD T-score ≤ -2.5. Linear and ordinal logistic regression analyses were performed. RESULTS: Among 320 patients with a median age of 37.3 years, body mass index (BMI) of 21.4kg/m(2) and 94.4% on cART, osteopenia and osteoporosis were diagnosed in 35.6% and 3.8%, respectively. On multivariate linear analysis, factors associated with reduced BMD were increasing age (p=0.006), longer duration on antiretroviral therapy (p=0.007), and a decreasing BMI (p=0.002). Using ordinal logistic regression, being underweight with a body mass index (BMI)<18.5kg/m(2) was independently associated with reduced BMD (proportional odds ratio, 4.12; 95% confidence interval, 1.93-8.82). CONCLUSION: Reduced BMD was prevalent among HIV-infected Taiwanese adults on cART. Increased age, lower BMI, and exposure to antiretroviral therapy were significantly associated with decrease of BMD.

Differential impact of resistance-associated mutations to protease inhibitors and nonnucleoside reverse transcriptase inhibitors on HIV-1 replication capacity.

The effects of drug resistance on HIV-1 replication capacity have been studied, but data from clinical isolates are few. We accessed the patients with HIV-1 infection at the National Taiwan University Hospital who experienced virological failure. Genotypic susceptibility and replication capacity of clinical HIV-1 isolates were measured. There were 80 patients enrolled between September 2007 and August 2010. The HIV-1 replication capacity declined significantly with the increasing number of major resistance-associated mutations (RAMs) to protease inhibitors (PIs) (p<0.001); however, it did not decline significantly with the increasing RAMs to first-line nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) (p=0.098). Regarding the effects of resistance to antiretroviral drugs in salvage therapy, decreased replication capacity was noted with the increasing RAMs to darunavir/ritonavir (p<0.001) and specific RAMs (L100I, K101P, and Y181C/I/V) to etravirine (p<0.001). Although NNRTI-related RAMs have less remarkable effects, both PI- and NNRTI-related RAMs reduced replication capacity, especially RAMs to darunavir/ritonavir and etravirine, which are commonly used in salvage therapy for treatment of patients infected with highly resistant HIV. Thus, decreased viral fitness during the emergence of RAMs suggests the importance of continued optimal antiretroviral treatment even when virological failure was noted.

Incidence of acute pancreatitis in human immunodeficiency virus-positive patients with hypertriglyceridemia: is it really high?

OBJECTIVE: To assess the incidence of acute pancreatitis in human immunodeficiency virus-positive patients with triglyceride (TG) greater than 500 mg/dL after highly active antiretroviral therapy. METHODS: Sequential TG levels during follow-up and episodes of acute pancreatitis were retrospectively reviewed in 347, 417, and 571 patients enrolled in periods 1 (2000-2002), 2 (2003-2005), and 3 (2006-2008), respectively. The incidence of acute pancreatitis, defined as consistent clinical symptoms and elevated amylase and/or lipase levels, was estimated. RESULTS: A total of 5356 TG measurements were performed during the follow-up for 698.22, 884.14, and 1215.69 person-years in periods 1, 2, and 3, respectively. Overall, 9.89% of patients had at least one TG greater than 500 mg/dL. Five patients with TG less than 500 mg/dL developed acute pancreatitis. The crude incidences of acute pancreatitis were 0.6%, 0.5%, and 0.2%, and the incidence rates were 2.86, 2.26, and 0.82/1000 person-years in periods 1, 2 and 3, respectively (all, P > 0.05). The incidence rates of acute pancreatitis when TG levels were less than 500, less than 1000, and less than 1500 mg/dL ranged from 1.2 to 4.9/1000 person-years, whereas it was 0/1000 person-years when TG levels were greater than 500, greater than 1000, and greater than 1500 mg/dL, respectively. CONCLUSION: The risk of acute pancreatitis was low among human immunodeficiency virus-positive patients who developed hypertriglyceridemia after receiving highly active antiretroviral therapy.