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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. Keywords: Comorbidity, Framingham equation, Atherosclerotic cardiovascular disease (ASCVD), Data-collection on adverse effects of anti-HIV drugs (D:A:D), Antiretroviral therapy

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) 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 β-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.

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 log 10 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.

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.

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.

A single strain of Mycobacterium massiliense (BRA 100), a subspecies of the Mycobacterium abscessus complex, has been responsible for an epidemic of post-surgical infections in Brazil. Outside Brazil, this is the first report to describe a single emerging strain of M. massiliense (TPE 101) associated with extrapulmonary infections. This phenomenon may be underestimated because sophisticated molecular typing of M. abscessus is not routinely performed. Our molecular epidemiology study was triggered by an outbreak investigation. Nine case isolates were grown from the surgical sites of nine mostly paediatric patients receiving operations from 2010 to 2011. All available non-duplicated isolates of M. abscessus during this period were obtained for comparison. Mycobacteria were characterized by multilocus sequence analysis (MLSA), repetitive sequence PCR (rep-PCR) and pulsed-field gel electrophoresis (PFGE). Of 58 isolates of M. abscessus overall, 56 were clinical isolates. MLSA identified 36 of the isolates as M. massiliense. All case isolates were indistinguishable by PFGE and named the TPE 101 pulsotype. Of the stored strains of M. abscessus, TPE 101 strains were over-represented among the control surgical wound (7/7, 100%) and subcutaneous tissue isolates (4/5, 80%) but rare among the respiratory isolates (1/16, 6%) and absent from external skin, ocular and environmental samples. In conclusion, a unique strain of M. massiliense has emerged as a distinctive pathogen causing soft tissue infections in Taiwan. Further study to identify whether this is due to an occult common source or to specific virulence factors dictating tissue tropism is warranted.

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

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.

BackgroundProlonged exposure to combination antiretroviral therapy (CART) may result in hyperlipidemia and other metabolic complications. This study aimed to evaluate the clinical, virologic, and immunologic outcomes in HIV-infected patients with hyperlipidemia whose CART was switched to atazanavir-containing antiretroviral regimens.MethodsIn this 48-week prospective, observational study that was conducted at designated hospitals for HIV care in Taiwan, HIV-infected patients aged 18 years or older who had developed hyperlipidemia after receiving CART that did not contain atazanavir were enrolled. Antiretroviral regimens were switched to regimens containing two nucleoside reverse-transcriptase inhibitors plus atazanavir 400mg once daily or atazanavir 300mg boosted with ritonavir 100mg once daily. The lipid profiles, including total triglycerides, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, CD4+ lymphocyte counts, and plasma HIV RNA load were determined every 3 months.ResultsSixty-six patients with hyperlipidemia were enrolled. At the end of the study, triglyceride levels declined by 49.0% (p=0.0002) and total cholesterol levels by 18.1% from baseline (p

Background Parvovirus B19 is associated with erythema infectiosum in children or arthralgia and arthritis in adults. The virus is relatively conserved and nucleotide identity is expected in viruses that are epidemiologically related. Here, we describe the first cluster of parvovirus infection among hospital staff documented in Taiwan. Methods Active surveillance was conducted in coronary care units (CCUs) at a 2200-bed teaching hospital for 1 month in 2007. A case defined clinically as occurring in a patient or staff in CCUs with new onset of fever or rash. Serum was tested for parvovirus B19 IgM and IgG by immunoblotting and DNA by nested polymerase chain reaction. When viremia was detected, nucleotide sequences were analyzed and compared with those of two clinical isolates. The attack rate was defined as the cumulative incidence of acute infection in CCU staff and patients during the study period. Results Among 57 staff and 15 patients, five nurses met the clinical case definition. Three had acute infection as demonstrated by viral DNA and IgM. The attack rate was 5.3% for the staff and zero for patients. Seroprevalence rate was lower in staff than in patients (26.3% vs. 53.3%). The isolates collected from three cases were highly similar to a community isolate, and they varied with each other by 2-6 nucleotides. The isolate collected from a nurse was identical to that from her friend 3 weeks apart and was concordant with mutual transmission. A sequence with 45 nucleotide variations was identified from a staff member with chronic infection who was negative for IgM and had only weak IgG anti-VP1 reaction with immunoblotting. We did not find any patient as the source of infection. Conclusion We identified a cluster of parvovirus infection that was caused by three circulating strains which did not support the hypothesis of transmission of a single strain in CCUs.

Background/PurposeNon-Hodgkin's lymphoma (NHL) is the second most common acquired immunodeficiency syndrome-defining malignancy with a high mortality rate. This study aimed to describe changes in the incidence and clinical characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in a referral hospital for HIV care.MethodsThe medical records of HIV-infected patients diagnosed with NHL between June 1994 and December 2006 were retrospectively reviewed. Risk stratification of each patient was evaluated using the International Prognostic Index (IPI). Case patients were followed at least for 2 years to assess the 2-year survival rates.ResultsDuring the 12-year period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of differentiation 4 count was 82 cells/μL (range, 2–477 cells/μL) at diagnosis. Before the introduction of highly active antiretroviral therapy (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year survival rate did not differ significantly between patients diagnosed in the pre-HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients receiving HAART for more than 6 months had better survival rates (p < 0.05). A low IPI score was a good prognostic factor predictive of a patient's outcome.ConclusionThe incidence of NHL in HIV-infected patients declined significantly in the HAART era. Despite the introduction of HAART, the short-term survival of the patients with NHL remained poor. The IPI was a good predictor for survival.

Background/Purpose: Human immunodeficiency virus (HIV)-infected patients are more susceptible to tuberculosis (TB), which might be the initial presentation of HIV infection. This study assessed the frequency and results of HIV testing among patients diagnosed with TB at a university hospital from 2000 to 2006. Methods: Surveillance data for all reported TB cases from 2000 to 2006 were reviewed to identify patients with unknown HIV serostatus who received HIV testing when TB was diagnosed. Trends in HIV testing among TB patients were examined, and factors associated with HIV infection were analyzed. Results: From 2000 to 2006, 3643 patients were diagnosed with TB, and 49 with HIV infection prior to TB diagnosis were excluded. Of the 3594 patients with unknown HIV status before TB diagnosis, 1035 (28.8%) were offered HIV testing. There was an increasing trend of providing HIV testing to TB patients that ranged from 16.1% to 43.7% (p＜0.001), and the overall prevalence of HIV infection among TB patients was 5.6% (95% CI, 4.3-7.1%) of those tested. Compared with TB patients without HIV infection, those with HIV infection were more likely to be aged ＜50 years [adjusted odds ratio (aOR), 8.0; 95% CI, 4.4-14.6), male (aOR, 7.1; 95% CI, 3.0-16.9), and present with extrapulmonary TB (aOR, 2.8; 95% CI, 1.7-4.6). Conclusion: The frequency of HIV testing among TB patients remained low at the university hospital providing TB and HIV care in Taiwan from 2000 to 2006. Among those tested for HIV infection, age＜50 years, male gender and presentation of extrapulmonary TB were associated with HIV infection.

We investigated the relationship between hypertriglyceridemia and the single-nucleotide polymorphisms (SNPs) on APOA5 in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) in Taiwan. Receipt of protease inhibitor-based HAART, high baseline triglyceride levels, and carriage of APOA5 SNP3 or c.553G>T variants or APOA5 SNP1T/ SNP2G/SNP3C/c.553T haplotype were statistically significantly associated with development of extreme hypertriglyceridemia (triglyceride level, >500 mg/dL).

Purpose: To determine the characteristics of cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU) in the era of highly active antiretroviral therapy (HAART). Methods: We reviewed data from 47 of 79 consecutive patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis. Results: The incidence of CMV retinitis in AIDS patients has markedly decreased over the recent 10 years. The characteristics of CMV retinitis have changed. Development of IRU occurred in 24.4%. Conclusions: Symptomatic IRU develops in a significant number of patients with inactive CMV retinitis following successful HAART. Eyes with IRU respond favorably to antiinflammatory therapy without reactivation of retinitis.

Risk of recurrent nontyphoid Salmonella (NTS) bacteremia and trends of antimicrobial resistance of NTS remain unknown in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART).Ninety-three patients who received a diagnosis of NTS bacteremia from June 1994 through June 2006 were prospectively followed up. Incidence of recurrent NTS bacteremia was compared between the pre-HAART era (June 1994-March 1997) and the HAART era (April 1997-June 2006). Prevalence of antimicrobial resistance was compared among the NTS isolates obtained in the pre-HAART era, the early HAART era (April 1997-June 2002), and the late HAART era (July 2002-June 2006).Compared with patients enrolled in the pre-HAART era, patients who received HAART had an incidence of recurrent NTS bacteremia that was significantly reduced by 96%; the incidence of recurrent NTS bacteremia was 2.56 cases per 100 person-years in the HAART era, compared with 70.56 cases per 100 person-years in the pre-HAART era (rate ratio, 0.036; 95% confidence interval, 0.012-0.114; P.001). In the HAART era, the incidence of recurrent NTS bacteremia did not increase among patients receiving fluoroquinolone prophylaxis foror=30 days (1.69 cases per 100 person-years), compared with among patients receiving fluoroquinolones for30 days (3.95 cases per 100 person-years), with a rate ratio of 0.43 (95% confidence interval, 0.07-2.58). Although resistance to ampicillin, cotrimoxazole, and chloramphenicol decreased, the proportion of NTS isolates resistant to fluoroquinolones increased from 0% in the pre-HAART era to 6.2% in the early HAART era and 34.2% in the late HAART era (P=.002).The risk of recurrent NTS bacteremia decreased significantly in the HAART era, although NTS isolates obtained from HIV-infected patients were increasingly resistant to fluoroquinolones.

To know why HIV-1-infected persons are particularly susceptible to amebic liver abscess (ALA), we investigated the role of CD4 + CD25 + T cells in the susceptibility of HIV-1-infected persons to this disease. Herein we show, in early stage HIV-1-infected subjects, that CD4 + T-cell responses to Entamoeba histolytica antigen (EhAg) were selectively impaired, especially in those with ALA. EhAg-specific CD4 + T-cell responses were normalized by depletion of CD4 + CD25 + cells or by addition of anti-cytotoxic T lymphocyte antigen 4 (CTLA4) antibody. Regulatory activity of CD4 + CD25 + T cells to suppress the EhAg-specific CD4 + T-cell response could be induced by EhAg-primed dendritic cells (DCs) in HIV-1-infected subjects, especially in those with ALA, but not in healthy controls. Exogenous Tat-incubated DCs derived from HIV-negative subjects also could upregulate CTLA4 expression on autologous CD4 + CD25 + T cells and selectively suppress the EhAg-specific CD4 + T-cell response. The results imply an interaction of the two pathogens: HIV-1, perhaps through the effect of Tat on DCs, may upregulate EhAg-specific regulatory T-cell activity to suppress T-cell response to E. histolytica, thus increasing the susceptibility to invasive amebiasis in even early-stage HIV-1-infected persons.

Between June 1994 and May 2003, 93 of 716 (13.0%) HIV-infected patients with a median baseline cell differentiation CD4+ count of 61 x 10(6) cells/L (range, 1-1206 x 10(6) cells/L) developed 103 episodes of herpes zoster [HZ], with an incidence of 5.67 per 100 person-years (PY). The incidence of HZ in the pre-highly active antiretroviral therapy (HAART) era (17.21 per 100 PY) was significantly higher than that in the post-HAART era (5.05 per 100 PY) (P < 0.0001). In the first six months of enrollment, the incidence of HZ was significantly higher than that between six and 12 months both in the pre-HAART (27.65 per 100 PY versus 8.43 per 100 PY, P = 0.02) and post-HAART era (17.79 per 100 PY versus 3.39 per 100 PY, P < 0.0001). In multivariate analyses, only baseline CD4+ count remained a significant risk factor associated with HZ. HZ did not increase mortality rate either in the pre-HAART or post-HAART era, although the risk for HIV progression was significantly higher in patients with HZ (adjusted odds ratio [OR], 1.747, 95% confidence interval, 1.037-2.943). We conclude that the incidence of HZ was highest in the first six months of enrollment in patients at late stage of HIV infection, which did not increase with the introduction of HAART. Baseline CD4+ lymphocyte count was the most significant risk factor associated with development of HZ. HZ was associated with increased risk for HIV progression, but not mortality.

59:535-7. 7. Vallieres E, Jamieson C, Haber GB, Mackenzie RL. Pancreaticoduodenal necrosis after endoscopic injection of cyanoacrylate to treat a bleeding duodenal ulcer: a case report. Surgery 1989;106:901-3. 8. Cheah WK, So J, Chong SM, Goh P. Duodenal ulcer perforation following cyanoacrylate injection. Endoscopy 2000;32:S23. 9. Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD. A prospective, randomized trial of largeversus small-volume endoscopic injection of epinephrine for peptic ulcer bleeding. Gastrointest Endosc 2002;55: 615-9. Division of Gastroenterology, Department of Medicine, National University Hospital, Singapore.

In order to prevent transmission of hospital-acquired vancomycin-resistant enterococci (VRE), the infection control team (ICT) of the National Taiwan University Hospital (NTUH) introduced practical guidelines from January 1997 to June 2000. All patients at NTUH found to be infected or colonized with VRE were placed in strict contact and cohort isolation. Surveillance cultures were obtained from other patients in close proximity in order to determine any spread of VRE. If identified, these patients were also placed in contact and cohort isolation, and their isolates were subjected to antimicrobial susceptibility testing and molecular typing by pulsed-field gel electrophoresis. During this period, 20 patients were found to have VRE. Based on typing results, there were three occasions where the same VRE strain had spread between index patients and roommates or patients staying in neighbouring rooms. No further spread occurred after applying strict contact isolation for these patients. The hospital-acquired VRE infection rate was around 0.03 to 0.09 per 1000 discharges during the intervention period. After July 2000, however, members of the ICT did not actively monitor or implement any interventions to control VRE. The rate then increased to 0.20 per 1000 discharges in 2001. This study suggests that interventions for the control of VRE, based on the guidelines from the Hospital Infection Control Practice Advisory Committee, are effective for control of VRE spread. Failure to adhere to these guidelines may result in an increase in hospital-acquired VRE.

To assess the impact of vaccination with 23-valent pneumococcal polysaccharide vaccine on the risks for development of pneumococcal disease, all-cause community-acquired pneumonia, HIV progression, and mortality and immunologic and virologic responses among HIV-1-infected patients treated with highly active antiretroviral therapy (HAART), we conducted a 2-year prospective observational cohort study at a university hospital in Taiwan. A total of 305 HIV-1-infected patients who received 23-valent pneumococcal vaccine (vaccinees) and 203 patients who did not (non-vaccinees) were prospectively observed between 1 June 2000 and 31 October 2002. Changes of CD4+ and plasma viral load (PVL) from baseline to week 4 of vaccination were assessed in 31 randomly selected vaccinees. The incidence of pneumococcal disease and bacteremia of vaccinees was 2.1 per 1000 patient-years (PY) (95% confidence interval (95% CI), 1.7-2.5 per 1000 PY) over the median observation of 641 days (range, 37-832 days) following vaccination while that of non-vaccinee was 21.8 per 1000 PY (95% CI, 20.1-23.7 per 1000 PY) and 7.3 per 1000 PY (95% CI, 7.0-7.6 per 1000 PY), respectively, over the observation of 500 days (range, 32-851 days), with an adjusted odds ratio (AOR) for developing pneumococcal disease of 0.085 (95% CI, 0.010-0.735) and for bacteremia of 0.22 (95% CI, 0.018-2.561). The median CD4+ count increased by 45 x 10(6) l(-1) (P = 0.01) and median PVL change was 0 log(10) copies/ml (range of decrease, -0.74 to 2.47 log(10) copies/ml) after 1 month of pneumococcal vaccination among the subgroup of 31 vaccinees receiving HAART. The median CD4+ count increase from baseline to the end of study was 149 x 10(6) l(-1) for vaccinees and 107 x 10(6) l(-1) for non-vaccinees (P = 0.21). The AOR of developing all-cause community-acquired pneumonia and new AIDS-defining opportunistic illnesses (OI) of vaccinees as compared to non-vaccinees was 1.876 (95% CI, 0.785-4.485) and 0.567 (95% CI, 0.217-1.484), respectively. Death rate of vaccinees and non-vaccinees was 17.7 per 1000 PY (95% CI, 16.5-18.9 per 1000 PY) and 80.5 per 1000 PY (95% CI, 77.1-83.9 per 1000 PY), respectively. Adjusted hazard ratio for death of vaccinees as compared with non-vaccinees was 0.733 (95% CI, 0.236-2.274). Our data suggested that vaccination with 23-valent pneumococcal polysaccharide vaccine and receipt of HAART were associated with reduced risks for pneumococcal disease among HIV-1-infected patients receiving HAART. Vaccination did not increase the risks of all-cause community-acquired pneumonia, HIV progression, and mortality. Vaccination did not increase PVL or decrease CD4+ among HIV-1-infected patients receiving HAART.

Lupus cystitis was rare but frequently resulted in obstructive uropathy and had a strong association with gastrointestinal(GI) symptoms. We treated six patients with systemic lupus erythematosus(SLE) and obstructive uropathy from January 1996 to December 2001 in a university hospital. Evidence of cystitis was obtained from cystoscopic biopsy or the presence of thickened bladder wall in image study. Similar to other reports, five patients had GI manifestations such as abdominal pain, nausea/vomiting, diarrhoea or ileus. In addition, mesenteric lymphadenopathy or pancreatitis was noted in three patients. Two patients had been treated for idiopathic thrombocytopenicpurpura (ITP), four and 20 years ago, respectively. All six patients had antibodies to double-stranded DNA (dsDNA). Five patients each had antibodies to cardiolipin (IgG aCL) or SSA. The high prevalence of anti-SSA had also been reported in Chinese lupus patients with intestinal pseudo-obstruction, a clinical manifestation frequently associated with bilateral ureterohydronephrosis. Two patients died of intractable infection after the surgical procedures for persistent ureterohydronephrosis and both patients had antibodies to ribosomal P proteins. Lupus cystitis might not be so rare in Chinese patients with SLE. The diagnosis should be kept in mind when lupus patients have urinary and/or GI symptoms.

Background/Aims : The optimal strategy to prescribe highly active antiretroviral therapy (HAART) in patients infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) remains unsettled. This study aimed to compare the HBV dynamics between HBeAg-positive and HBeAg-negative coinfected patients treated with lamivudine-containing HAART. Methods : We retrospectively analyzed the serial changes of plasma HBV DNA levels in 24 HBsAg-positive HIV-infected patients who entered the HAART program. A polymerase chain reaction-based assay, capable of quantifying as few as 400 HBV copies/ml, was used. The median follow-up time was 18 months. Results : HAART containing lamivudine 300 mg/day effectively suppressed plasma HBV-DNA to 10 −3 –10 −5 -fold of the baseline levels, but a multi-phasic decay of HBV DNA was observed. The later phases became flat, as a persistent residual HBV viremia, in eight of the studied 10 HBeAg-positive patients; in contrast, residual HBV viremia was not observed in the 10 HBeAg-negative patients studied (8/10 vs. 0/10, P =0.0007, Fisher's exact test). HAART without lamivudine did not suppress plasma HBV DNA levels in the remaining four patients. Conclusions : HAART containing lamivudine 300 mg/day effectively suppress HBV replication in HBeAg-negative HIV/HBV-coinfected patients. Nevertheless, residual HBV replication persisted in most HBeAg-positive coinfected patients.

Acinetobacter baumannii is ubiquitous and has recently become one of the most important healthcare-associated (HA) pathogens in hospitals. Infection caused by this organism often leads to significant morbidity and mortality. Outbreaks of pan-drug resistant Acinetobacter baumannii (PDRAB) have rarely been reported. During a two-month period, an outbreak of PDRAB colonization and infection affecting 7 patients occurred in our surgical intensive care unit (SICU). The colonized sites were respiratory tract (N = 7) and central venous catheter (N = 2). One of the patients had a surgical wound infection. Extensive environmental contamination was identified, including sites such as bed rails, bedside tables, surface of ventilators and infusion pump, water for nasogastric feeding and ventilator rinsing and sinks. All of the isolates were analysed by pulsed-field gel electrophoresis (PFGE) and showed an identical pattern. After use of strict cohort nursing, hand hygiene environmental cleaning, and replacement of a dysfunctional high-efficiency particulate air filter (HEPA), the outbreak was controlled.

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.

In studying the epidemiology of parvovirus 4 (PARV4) in Taiwan, we detected DNA in plasma of 3 mothers and their newborns with hydrops. In 1 additional case, only the mother had PARV4 DNA. Our findings demonstrate that PARV4 can be transmitted through the placenta.

Invasive amebiasis rarely occurs in homosexual men and human immunodeficiency virus (HIV)-infected individuals and has not been regarded as a beacon for concomitant HIV infection. We encountered a bisexual man with a protracted course of amebic liver abscess and amebic colitis. In the presence of fever, generalized lymphadenopathy, and elevated serum aminotransferase levels, HIV infection was suspected and then confirmed by a de novo seroconversion of HIV antibody. Subsequently, we noted two consecutive patients with amebic liver abscess, also later found to be infected with HIV. The ameba obtained from these three cases was identified as Entamoeba histolytica by amplification of 16S ribosomal RNA by polymerase chain reaction and direct sequencing. This observation suggests that amebic liver abscess and colitis can be presentations for HIV infection in the Far East. Thus, the local patients with invasive amebiasis, especially those with a protracted course or with risk factors of HIV infection, should be tested for HIV.

Whether immunity against opportunistic pathogens can be fully restored by control of HIV-1 replication remains open to question. This longitudinal study was conducted to measure anti-tuberculosis (TB) cellular immunity in 13 HIV-1/TB-coinfected patients effectively treated by highly active antiretroviral therapy (HAART) in a period of 12 months. In this study, anti-TB cellular immunity was assessed by determining the frequencies of CD 69 expression on CD4+ and CD8+ T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4+CD69 to PPD and %CD8+CD69 to PPD). Here, we show that %CD4+CD69 to PPD correlated with the results of tuberculin skin tests and interferon-gamma (IFN-gamma) production from PPD-stimulated CD4+ T cells, and %CD8+CD69 to PPD also correlated with CD8+ T cell-mediated PPD-specific cytolysis. In overall analysis for these 13 patients, both %CD4+CD69 to PPD and %CD8+CD69 to PPD increased significantly during the 12 months (p =. 003 and p.001, respectively). However, we found %CD4+CD69 to PPD or %CD8+CD69 to PPD failed to increase substantially in some patients (i.e., immunologic nonresponders). A significantly higher proportion of patients whose baseline CD4+ count was50 cells/mm3 were considered to be CD4+ nonresponders compared with those whose baseline CD4+ count was50 cells/mm3. Furthermore, baseline CD4+ cell count in nonresponders is significantly lower than that in responders, although the effectiveness of HAART did not differ between them. Our results indicate that PPD-specific frequencies of CD69 expression may be used as surrogate markers of anti-TB cellular immunity. By this method, we show that full reconstitution of anti-TB cellular immunity in HIV-1/TB coinfected patients may not necessarily be achieved by "successful" HAART and may be influenced by the baseline immune status when HAART is started. These data suggest that the decision to discontinue secondary prophylaxis for opportunistic infections should be cautiously made, even when the CD4+ cell count has significantly increased.

Background: Diarrhea is a frequent gastrointestinal symptom in patients with acquired immunodeficiency syndrome (AIDS) and is a major source of morbidity and mortality. A stepwise diagnostic approach is often recommended to search for treatable causes. However, whether the stepwise diagnostic approach is adequate for planning treatment and whether specific treatment for infectious etiologies will affect the survival of patients with AIDS remain unknown. Methods: From March 1996 to September 1997, endoscopy was performed in AIDS patients with diarrhea, the etiology of which was not identified by noninvasive methods. Specific treatment was given according to the identified etiologies and symptomatic treatment was given for those without definite diagnosis. The clinical symptoms, signs, and duration of follow-up were recorded and survival patterns were analyzed. Results: Etiologic diagnoses were made in 26 of 40 patients (65%) who underwent endoscopic studies. Amebic colitis and cytomegalovirus colitis were the 2 leading causes of prolonged diarrhea in patients with AIDS. Thirty-five patients (87.5%) recovered after treatment. The difference in survival time after diarrhea between patients whose symptoms resolved after treatment and those who continued to have diarrhea was statistically significant (p < 0.001). Conclusions: Endoscopic studies were helpful for the diagnosis of prolonged diarrhea in AIDS patients who had negative stool studies and did not respond to 2 weeks of empiric treatment. Specific treatment according to the results of endoscopy may improve survival in these patients. (Gastrointest Endosc 2000;51:427-32.)

Chow-In Ko, MD, Chien-Ching Hung, MD, Mao-Yuan Chen, MD, Po-Ren Hsueh, MD, Cheng-Hsiang Hsiao, MD, Jau-Min Wong, MD Diarrhea is the most common GI presentation of immunocompromised patients, especially those with acquired immunodeficiency syndrome (AIDS).1,2 More than 50% of patients with AIDS have diarrhea caused by a variety of pathogens during their illness.1,2 Intestinal mycoses are uncommon in immunocompromised patients, however, and may be caused by Cryptococcus neoformans3 and Histoplasma capsulatum.4 Penicillium marneffei, an emerging facultative intracellular pathogen and the only thermally dimorphic fungus of the genus Penicillium, can cause disseminated infection in patients residing in or traveling to areas where the organism is endemic, which include southeast Asia, southern China, and Hong Kong.5-17 With the human immunodeficiency virus (HIV) pandemic, the number of cases of penicilliosis marneffei has increased markedly during the past 5 years, from 30 cases during the period between 1973 and 1990 to more than 160 by the end of 1995.16 After extrapulmonary tuberculosis and cryptococcosis, penicilliosis marneffei ranks as the third most common opportunistic infection in HIV-infected patients in Thailand.14 Although P marneffei has become an increasingly important cause of invasive mycoses in immunocompromised hosts, it has been rarely implicated as a cause of intestinal mycoses. As of December 1997, only four cases of intestinal penicilliosis marneffei have been reported in English language publications and only one was diagnosed antemortem by endoscopy.8,9,12,17 Here we report three cases in which immunocompromised patients, two with AIDS and one after renal transplantation, presented with intestinal penicilliosis marneffei where early diagnosis was made possible by endoscopy.

Objective To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients. Design Prospective cohort study. Setting A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan. Methods From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases. To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens. Results A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified. Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08). The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses. Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC. The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60). Conclusion Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states. Those features may facilitate diagnosis and selection of specific therapeutic regimens. Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment. In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens. These results may emphasize the importance of prophylaxis for MAC in this population.

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

Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case-control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case-control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p

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.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.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, P0.05). 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.The risk of acute pancreatitis was low among human immunodeficiency virus-positive patients who developed hypertriglyceridemia after receiving highly active antiretroviral therapy.

To determine the impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome in areas where routine testing for drug resistance mutations may not be available before combination antiretroviral therapy (cART) is initiated.Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1349 antiretroviral-naive HIV-1-infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case-control study was conducted to assess the impact of TDR on treatment outcomes.The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003-06 to 5.1% in 2007-10. In the matched case-control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS2.5, initiation of regimens with GSS ≤2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P0.001). In patients receiving regimens with GSS ≤2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse-transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% CI 0.06-1.12, P = 0.07).In Taiwan the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS ≤2.5 was associated with poorer treatment responses than regimens with GSS2.5.

Background. The impact of hepatitis B virus (HBV) genotypes B and C on the clinical, immunologic, and virologic outcomes of human immunodeficiency virus (HIV)‐infected patients with chronic HBV infection remains largely unknown. Methods. Between January 1997 and December 2008, we enrolled 96 HIV-infected patients with HBV genotype B coinfection and 49 with genotype C coinfection; the patients were followed prospectively until December 2010. Clinical and immunologic outcomes in the context of HBV genotypes as well as the emergence of HBV DNA mutations conferring lamivudine resistance (rtM204I/V) were determined. Results. Themediandurationoflamivudine-containinghighlyactiveantiretroviraltherapy(HAART)was2.80years (interquartile range, 1.73‐5.92 years). The 2 groups of HIV-infected patients were comparable in age, sex, baseline HIV profiles, and liver function profiles. Compared with HIV-infected patients with HBV genotype C coinfection, those with genotypeB coinfection had a higher risk of hepatitisflares (43.8% vs 26.5%;P 5 .04), liver disease-related death (9.4% vs 0%; P 5 .03), hepatitis B e antigen (HBeAg) seroconversion (61.5% vs 25.0%, P 5 .03), and development of lamivudine resistance (31.3% vs 12.2%; P , .0001). No differences were observed between the 2 groups in terms of the development of hyperbilirubinemia, cirrhosis, or virologic and immunologic responses to HAART. Conclusions. Although therapeutic responses to long-term lamivudine-containing HAART were comparable between HIV-infected patients with HBV genotypes B and C coinfection, patients with genotype B coinfection were more likely to experience acute exacerbations of hepatitis, HBeAg seroconversion, lamivudine resistance, and liver disease‐ related death than those with genotype C coinfection. Hepatitis B virus (HBV) infection is an important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) worldwide [ 1 ]. Due to shared modesoftransmission,coinfection with HBV and human

Background The transmission routes of PARV4 are not completely understood. The first PARV4 serological study suggested that PARV4 is transmitted predominantly through parenteral route. Objectives To set up an immunoblot system for studying the epidemiology of PARV4 infection in HIV-1 infected patients in Taiwan. Study design Recombinant fusion proteins SUMOVP2 (a.a. 272–630 of PARV4 open reading frame 2) and SUMOVP3 (a.a. 604–914) were made and used as antigens in immunoblot. Plasma samples were from HIV-1 infected intravenous drug users IDU (69), homosexuals (66) and heterosexuals (68). Results PARV4 IgG seropositive rate was 73.9%, 71.2% and 58.8%; IgM seropositive rate was 40.5%, 16.7% and 17.6% in IDUs, homosexuals and heterosexuals, respectively. Longitudinal samples were available from two homosexuals positive for IgM anti-PARV4, persistent IgM response was found over a period of 9 and 21 months, respectively. Conclusions PARV4 is a common viral infection in HIV-1 infected homosexuals and heterosexuals in Taiwan. The detection of IgM anti-PARV4 does not always suggest recent PARV4 infection.

Background Risk of pneumocystosis after discontinuation of primary or secondary prophylaxis among HIV-infected patients before CD4 counts increase to ≧200 cells/μL (early discontinuation) after receiving highly active antiretroviral therapy (HAART) is rarely investigated. Methods Medical records of 660 HIV-infected patients with baseline CD4 counts Results The incidence rate of pneumocystosis after HAART was 2.81 per 100 person-years among 521 patients who did not initiate prophylaxis or had early discontinuation of prophylaxis, which was significantly higher than the incidence rate of 0.45 per 100 person-years among 139 patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL (adjusted risk ratio, 5.32; 95% confidence interval, 1.18, 23.94). Among the 215 patients who had early discontinuation of prophylaxis after achievement of undetectable plasma HIV RNA load, the incidence rate of pneumocystosis was reduced to 0.31 per 100 person-years, which was similar to that of the patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL (adjusted risk ratio, 0.63; 95% confidence interval, 0.03, 14.89). Conclusions Compared with the risk of pneumocystosis among patients who continued prophylaxis until CD4 counts increased to ≧200 cells/μL after HAART, the risk was significantly higher among patients who discontinued prophylaxis when CD4 counts remained

Kaposi's sarcoma (KS) continues to occur in patients with human immunodeficiency virus (HIV) infection in the era of highly active antiretroviral therapy (HAART), and remains the most common HIV-associated malignancy. This retrospective study was conducted to describe the change in incidence and characteristics of HIV-associated KS in Taiwan.The medical records of patients with HIV infection who received a diagnosis of KS at the National Taiwan University Hospital between June 1994 and March 2008 were reviewed.During the 14-year study period, 62 HIV-infected patients were diagnosed with KS, which included 40 definite diagnoses (64.5%) by pathology and 22 probable diagnoses (35.5%) ascertained by characteristic lesions, compatible clinical manifestations, and response to treatment. Most of the patients were men who have sex with men (MSM; n = 53; 85.5%). At the time of diagnosis of KS, the median CD4 count was 20 cells/microL (range, 1-371 cells/microL). A considerable decline in the incidence of KS in HIV-infected patients since the introduction of HAART was demonstrated; in the pre-HAART era, 18 of 175 patients (10.3%; 95% confidence interval [CI], 6.53- 15.75) developed KS, compared with 44 of 1615 patients in the HAART era (2.7%; 95% CI, 2.03-3.65) [p0.0001]. The prognosis of HIV-infected patients with KS has improved since the introduction of HAART, as the mortality rate has declined from 77.8% in the pre-HAART era to 34.1% in the HAART era (p = 0.002).The incidence of KS in HIV-infected patients and the mortality rate of these patients significantly declined in the HAART era, although KS continued to occur in patients with advanced HIV infection.

AIMS Patients with Sjögren's syndrome (SS) are reported to have an increased severity of irritating bladder symptoms, including urinary frequency and urgency. The mechanism remains unclear. The aim of this study is to elucidate the possible etiologies underlying this problem.Data from 23 female patients with SS (15 primary and 8 secondary) who were treated in the urology clinic for chronic, irritating bladder symptoms were studied. Evaluation of each subject is composed of lower urinary tract symptoms (LUTS), bladder diary entries, and urodynamic studies, which also included an ice water test (IWT) to detect the presence of a C-fiber mediated micturition pathway. Interstitial cystitis (IC) was diagnosed with post-hydrodilatation cystoscopic findings of glomerulations and a KCl test.These patients complained predominantly of overactive bladder symptoms (OAB), including frequency (n=20, 87%), nocturia (n=16, 66%), and urgency (n=12, 52%). Based on the aforementioned evaluations, four patients (17%) had polyuria with normal bladder function, nine patients (39%) had detrusor overactivity (DO), seven patients (32%) had bladder hypersensitivity (including two patients (9%) diagnosed with IC), and three patients (13%) had negative findings. Ice water instillation neither elicited novel involuntary contractions, both in those with or without DO. Five of the six patients (83%) with DO versus one of the four patients (25%) without DO responded to antimuscarinic therapy.Various factors contribute to the irritating bladder symptoms in patients with SS, with DO being predominant. The LUTS developed in patients with SS are not due to any specific single etiology and that each patient must be individually carefully evaluated.

Clinical manifestations and outcome of toxoplasmic encephalitis (TE) in patients at late stage of human immunodeficiency virus (HIV) infection have not been previously reported in Taiwan. The aim of this study was to describe the clinical and radioimaging characteristics and treatment response in HIV-infected patients with TE in Taiwan.Medical records of all HIV-infected patients who were diagnosed as having TE between June 1994 and December 2006 at the National Taiwan University Hospital, Taipei, Taiwan, were reviewed by use of a standardized case record form. Diagnosis of TE was based on clinical manifestations, serology, and radioimaging findings plus clinical and radiographic response to anti-toxoplasmosis therapy.During the 12-year study period, 18 patients (1.2%) with 19 episodes of TE were identified. The median CD4+ lymphocyte count was 15 cells/microL and plasma HIV RNA load was 179,000 copies/mL at the diagnosis of TE. TE was the initial presentation of HIV infection in around two-thirds of the patients. Fever, focal neurological deficit, cognitive dysfunction, and altered mental status were the most common presenting symptoms. The typical radioimaging findings, multiple enhanced lesions with mass effect, were most common in the cerebral cortex, followed by the basal ganglia, cerebellum and brain stem. Compared with those who survived TE, the 3 patients who died of TE were older (52 vs 37 years, p=0.016) and had a higher incidence of cognitive impairment (100.0% vs 37.5%, p=0.063) and altered mental status (100.0% vs 18.8%, p=0.025).TE was a rare HIV-related infectious complication in our cohort. Advanced age and altered mental status were associated with an increased mortality in HIV-infected patients with TE.

The seroprevalence of viral hepatitis and spectrum of infectious complications among human immunodeficiency virus (HIV)-infected injection drug users (IDUs) remains unclear in Taiwan, although there has been a significant increase in the prevalence of HIV infection among IDUs in the last 2 to 3 years.The medical records of HIV-infected IDUs who sought medical care at a referral hospital for HIV care from June 1994 to December 2006 were retrospectively reviewed. A standardized case record form was used to collect demographic, clinical, laboratory and microbiologic data.During the 12-year study period, a total of 102 HIV-infected IDUs with a median age of 39.5 years (range, 19 to 73 years) sought HIV care at the referral hospital. The male-to-female case ratio was 6 and males were significantly older than females (39.5 vs 28 years, p0.001). The overall median CD4+ cell count and plasma HIV RNA load by reverse transcriptase-polymerase chain reaction at enrollment were 374 cells/microL and 4.45 log(10) copies/mL, respectively. The CD4+ cell count of HIV-infected IDUs enrolled after year 2003 was significantly higher than those enrolled before 2003 (438 vs 23 cells/microL, p0.001). The seroprevalence of hepatitis C virus (86.6% overall) increased over time, while that of hepatitis B virus decreased in the patients born after 1984, when nationwide hepatitis B vaccination was started in Taiwan. Gram-positive bacteria were causative for 69.7% of the 33 bacteremic episodes, and Staphylococcus aureus was the leading pathogen (16 episodes), with methicillin-sensitive S. aureus accounting for 11 bacteremic episodes (33.3%). The most common bacterial infection was infective endocarditis. Tuberculosis occurred more frequently in men, and extrapulmonary tuberculosis was more common than pulmonary tuberculosis and was associated with a lower CD4+ count.Bacteremia, infective endocarditis and tuberculosis were the three most common patterns of infection among HIV-infected IDUs who sought medical care at a referral hospital; and methicillin-sensitive S. aureus was the most common etiology of bacteremia. The high seroprevalence of hepatitis B and C and subsequent hepatic complications may present a future challenge to the health care system.

Purpose Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated. Results Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis. Conclusion While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.

To determine the prevalence and trends of antiretroviral drug resistance among HIV-1-infected Taiwanese patients who have been provided with free-of-charge antiretroviral therapy (ART) since 1990.Blood samples collected from 786 HIV-1-infected patients from 1999 to 2006 were subjected to genotypic resistance assay. Antiretroviral resistance mutations were identified in accordance with the antiretroviral resistance mutation list of the International AIDS Society-USA Consensus Guidelines. Trends of resistance were studied in patients enrolled in two periods: before (period 1, January 1999 to December 2003) and after (period 2, January 2004 to December 2006) the CRF07_BC outbreak among injection drug users (IDUs).The frequency of HIV-1 isolates harbouring one or more primary mutations associated with antiretroviral resistance to reverse transcriptase inhibitors or protease inhibitors increased significantly from 6.6% in period 1 to 12.7% in period 2 (P = 0.003). A significant increase in prevalence of antiretroviral drug resistance was observed among men who have sex with men and patients infected with HIV subtype B. In multivariate analysis, hepatitis C virus (HCV) exposure, which exhibited collinearity with injection drug use and infection with CRF07_BC, represented a lower risk for infection with resistant viruses.Our findings suggest that the prevalence of antiretroviral resistance has increased in Taiwan over the past 8 years after the introduction of combination ART. IDUs who were HCV-seropositive and infected with CRF07_BC were at lower risk for infection with antiretroviral-resistant viruses.

Osteonecrosis, a disabling complication associated with antiretroviral therapy (ART) and human immunodeficiency virus (HIV) infection, has rarely been reported in an Asian population. After an observation of 3,250 person-years (PY), 11 of 967 (1.1%) HIV-infected patients at a median age of 34 years developed osteonecrosis involving the hip joints (incidence, 3.4 per 1,000 PY). Their median CD4+ lymphocyte count had increased from 35 cells/microL at the diagnosis of HIV infection to 297 cells/microL at the diagnosis of osteonecrosis. The crude rate of osteonecrosis increased from 0% in patients without exposure to ART to 2.6 and 1.7% in patients with exposure to nucleoside reverse transcriptase inhibitors (NRTIs) and who had undergone highly active antiretroviral therapy (HAART) for 5 years or longer, respectively (P=0.18 and 0.09, respectively). Among the patients receiving HAART, the estimated incidence of osteonecrosis was 4.2 per 1,000 PY. Patients with osteonecrosis had a longer duration of exposure to NRTIs (1,641 versus 1,264 days, P=0.26) and to HAART (1,603 versus 1,251 days, P=0.42), a higher serum triglyceride (median, 1,130 versus 351 mg/dL; P=0.09), and a higher proportion of lipodystrophy (81.8 versus 15.0%, P0.0001). Our report suggests that osteonecrosis is a rare complication in HIV-infected patients with prolonged exposure to ART with resultant metabolic complications.

Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART).During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers.After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively.Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.

We compared changes in the relative frequencies of opportunistic illnesses (OIs) among 1,044 Taiwanese persons with HIV infection who were enrolled in three study periods from June 1994 to June 2004: before the introduction of highly active antiretroviral therapy (HAART); early HAART; and late HAART. Nearly two-thirds of those newly diagnosed with HIV infection had CD4 counts below 200/mm(3). Among a total of 1,182 OIs, candidiasis, Pneumocystis carinii pneumonia, and tuberculosis were the most common in all three study periods within 3 months after enrollment. Within 3 to 12 months after enrollment, the number of OIs declined significantly. Only 81 cases of OIs were diagnosed, the most common of which were cytomegalovirus disease, tuberculosis, candidiasis, and Mycobacterium avium complex infection. Except for the decreasing frequency of Kaposi's sarcoma, there was no significant change in the relative frequency of each individual OI within 3 months and within 3-12 months after enrollment across the three study periods. We concluded that despite the significant decrease in the number of AIDS-related OIs, the relative frequencies of common OIs did not change significantly after the introduction of HAART.

We assessed the survival of 1,044 HIV-infected persons enrolled in three periods: period 1, 1994 to 1997 (before the introduction of highly active antiretroviral therapy [HAART]); period 2, 1997 to 2000 (early-HAART); and period 3, 2000 to 2004 (late-HAART). As of 30 June 2005, 259 (24.8%) persons had died after a median observation duration of 985 days (range, 2 - 4,025 days). The mortality rate declined from 33.75 per 100 person-years in the pre-HAART era to 6.51 per 100 person-years in the late-HAART era (P0.0001). The adjusted hazard ratios for death in persons with a baseline CD4 count of200 cells/mul in periods 2 and 3 were 0.605 (P = 0.007) and 0.371 (P0.0001), respectively, when compared with persons enrolled in period 1; the adjusted hazard ratio for death was 0.611 for persons enrolled in period 3 when compared to period 2 (P = 0.01). Our study suggested that the survival of persons in the late stage of HIV infection in Taiwan continued to improve in the late HAART era.

This study evaluated the feasibility of reducing the indinavir (IDV) dosage in Taiwanese patients receiving the standard IDV/ritonavir (RTV) dosage of 800/100 mg twice a day who had undetectable plasma human immunodeficiency virus type 1 (HIV-1) RNA but had developed IDV-related toxicities. After dosage reduction to IDV/RTV 600/100 mg twice a day, the dose-related toxicity decreased and plasma HIV RNA remained undetectable at 24 weeks post-switch in all patients. The maximal plasma concentration (Cmax) and area under the plasma concentration-time curve of IDV decreased significantly (median, 6.3 vs 4.3 microg/mL and 1892 vs 1292 microg.min/mL, p=0.01 and 0.001, respectively) but the minimal plasma concentration remained at a similar level (median, 1.0 vs 0.8 microg/mL, p=0.12). This study found that the reduction in the dosage of IDV in HIV-1 infected patients receiving the standard IDV/RTV regimen guided by therapeutic drug monitoring decreased the Cmax, dose-related toxicity and medical cost without compromising viral control.

The Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a self-limiting lesion of unknown cause first described in 1972 independently by Kikuchi and Fujimoto et al. This self-limiting disorder usually occurs in Asian women in their late 20s or early 30s. Typically, it runs a benign course and appears to resolve spontaneously 1 to 6 months after definite diagnosis. The Kikuchi-Fujimoto disease usually manifests as a localized cervical lymphadenopathy; therefore, most patients with this disease are seen in ears, nose, and throat practice. Nodal involvement other than in the neck area or extranodal involvement is rare. In this situation, however, the Kikuchi-Fujimoto disease is easily confused with other less-benign conditions. We describe a case of Kikuchi-Fujimoto disease in a 30-year-old man that presented as a parotid gland tumor. This is the third study to document intraparotid Kikuchi-Fujimoto disease in the English literature. Our report illustrates the clinical features of this unusual condition and emphasizes potential confusion with other diagnoses.

Nosocomial bloodstream infection (NBSI) is common in patients with human immunodeficiency virus (HIV) infection. This study evaluated the incidence, causative pathogens, and outcome of NBSIs in hospitalized HIV-infected patients at a university hospital in Taiwan.The medical records of all HIV-infected patients who developed NBSIs from June 1994 to June 2003 were retrospectively reviewed. A standardized case record form was used to collect demographic, clinical, laboratory, and microbiologic data.During the study period, 57 episodes of NBSIs occurred in 51 HIV-infected patients whose median age was 37 years (range, 23 to 60 years). All of the patients were at HIV infection stage C. The incidence of NBSIs was 2.3 per 1000 person-days of hospitalization (41.4 per 1000 discharges). More than three-fourths of the 57 episodes (77.2%) were classified as primary NBSIs. Other infection foci included respiratory tract (6 episodes), urinary tract (3), surgical site (2), and skin (2). Staphylococcus species were the leading pathogens (42.1%). The crude and attributable mortality rates in patients with NBSIs during the study period were 38.6% and 26.1%, respectively. Multivariate analysis using a logistic regression model revealed that shock and hypoalbuminemia at the onset of NBSIs were the 2 factors predictive of mortality.NBSIs in hospitalized patients in the late stage of HIV infection were associated with a high attributable mortality rate. Staphylococcus species were the leading pathogen responsible for NBSIs. Presentations of shock and hypoalbuminemia were predictive of mortality.