Significance of Decreasing Rate of HIV and HBV Co-infection in a Nationwide Korean HIV/AIDS Cohort.

From December 2006 to December 2016, 1093 human immunodeficiency virus (HIV) individuals < 70 years enrolled in Korea human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) cohort were analyzed to investigate the prevalence of HIV/HBV co-infection rate and hepatitis B virus surface antibody (HBsAb) positive rate based on birth year. The HBV co-infection prevalence rate was the highest (8.8%) in patients born between 1960 and 1964 and the lowest (0%) among those born between 1995 and 1999. A decreasing linear trend of HBV co-infection rate was observed according to the 5-year interval changes. HBsAb-positive rate was only 58.1% in our study. The national HBV vaccination programs have effectively lowered the HBV co-infection rate in HIV population. However, it is identified that the HIV population has low HBsAb positive rate. Further evidences supporting efficacy of booster immunization for HBsAb negative HIV patients are required and efforts should be made to increase HBsAb positive rates among HIV patients to prevent horizontal transmission.

A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock.

PURPOSE: The purpose of our study was to investigate whether a simple scoring system based on the red blood cell distribution width (RDW), delta neutrophil index (DNI), and platelet count was associated with the prognosis of patients with sepsis, and whether this scoring system was more useful than each individual parameter. MATERIALS AND METHODS: We conducted a retrospective cohort study involving adult patients who received intensive therapy due to severe sepsis and septic shock from January 2010 to December 2015 at a tertiary teaching hospital in South Korea. RESULTS: A total of 730 patients were included in this study. Each patient was rated on a scale of 0 to 3 according to the new scoring system using the platelet count, RDW, and DNI. Point values were assigned based on the following definitions: RDW > 14.5%, DNI > 5.0%, and platelet count < 150 000/mm3. The 28-day mortality rate was 12.6% (92/730). The nonsurvivors had higher scores than the survivors (2.05 ± 0.80 vs 1.06 ± 0.87, P < .001). In the multivariate Cox proportional hazard analysis, the scoring system was an independent predictor of the 28-day mortality. The scoring system was well calibrated (P = .81 for the goodness-of-fit test) and discriminated (area under the receiver operating characteristic curve = 0.785). CONCLUSION: Our new scoring system using the RDW, DNI, and platelet count was useful for predicting the mortality in patients with severe sepsis and septic shock.

Significance of Increased Rapid Treatment from HIV Diagnosis to the First Antiretroviral Therapy in the Recent 20 Years and Its Implications: the Korea HIV/AIDS Cohort Study.

From December 2006 to December 2016, 1,429 patients enrolled in the Korea human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Cohort Study were investigated. Based on the year of diagnosis, the time interval between HIV diagnosis and initiation of antiretroviral therapy (ART) was analyzed by dividing it into 2 years. The more recent the diagnosis, the more likely rapid treatment was initiated (P < 0.001) and the proportion of patients starting ART on the same day of HIV diagnosis was increased in 2016 (6.5%) compared to that in 2006 (1.7%). No significant difference in the median values of CD4+ cell counts according to the diagnosis year was observed. In the past 20 years, the time from the HIV diagnosis to the initiation of ART was significantly reduced. Rapid treatment was being implemented at the HIV diagnosis, regardless of CD4+ cell count. Considering the perspective "treatment is prevention," access to more rapid treatment is necessary at the time of HIV diagnosis.

Impact of matrix-assisted laser desorption/ionization time of flight mass spectrometric evaluation on the clinical outcomes of patients with bacteremia and fungemia in clinical settings lacking an antimicrobial stewardship program: a pre-post quasi experimental study.

BACKGROUNDS: Several studies have evaluated the impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined with antimicrobial stewardship in patients with positive blood cultures; clinical outcomes improved. However, in many hospitals, antimicrobial stewardship is not available because of restricted medical resources. Thus, we investigated the impact of evaluation by MALDI-TOF MS on the clinical outcomes of patients with bacteremia and fungemia treated in a clinical setting lacking an antimicrobial stewardship program (ASP). METHODS: We designed a pre-post quasi experimental study and retrospectively reviewed the medical records of patients aged > 18 years old with bacteremia and fungemia during two periods: October-December 2012 and October-December 2013. Conventional methods were used to detect microbial pathogens in 2012, and MALDI-TOF MS was employed in 2013. Clinical outcomes compared between periods were the time to pathogen identification, time to effective therapy, 30-day all-cause mortality, time to microbiological clearance, length of ICU stay, and rate of recurrence of the same bloodstream infection (BSI). RESULTS: A total of 556 patients were enrolled; 302 patients in 2012, and 254 in 2013. The use of MALDI-TOF MS without an ASP reduced the time to pathogen identification (86.4 vs. 63.5 h, P < 0.001) but did not significantly reduce the time to effective therapy (27.4 vs. 23.2 h, P = 0.187). Also, none of the following differed significantly between the two periods: mortality (17.5 vs. 15.7%, P = 0.571), the time to microbiological clearance (3.6 vs. 3.7 days, P = 0.675), the length of ICU stay (16.8 vs. 14.7 days, P = 0.706), and the recurrence rate of the same BSI (5.0 vs. 2.8%, P = 0.183). CONCLUSIONS: The use of MALDI-TOF MS alone in a setting lacking an ASP did not afford clinical benefits. An ASP combined with MALDI-TOF MS is necessary to improve clinical outcomes.

Comparison of the efficacy of nafcillin and glycopeptides as definitive therapy for patients with methicillin-susceptible Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.

Chronic kidney disease with genitourinary tuberculosis: old disease but ongoing complication.

BACKGROUND: Genitourinary tuberculosis (GUTB) is a type of extrapulmonary TB that exerts a deleterious effect on renal function by promoting renal calcification and ureteric stricture. Therefore, we investigated the risk factors for chronic kidney disease (CKD) in GUTB patients after the end of treatment. METHODS: This retrospective study was conducted at a tertiary hospital in South Korea. Data from patients (>18 years of age) with GUTB were collected from January 2005 to July 2016. CKD was defined as a glomerular filtration rate <60 mL/min/1.73m2 after the end of treatment. RESULTS: In total, 56 patients with GUTB (46.4% males; mean age 52.8 ± 16.6 years) were enrolled in the study. CKD developed in 11 (19.6%) patients and end-stage renal disease in 4 (7.1%). In a univariate analysis, older age (p = 0.029), microscopic haematuria (p = 0.019), proteinuria (p = 0.029), acute renal failure (ARF) (p < 0.001) and a positive polymerase chain reaction-based test result for TB in the urine (p = 0.030) were significantly associated with decreased renal function. In a multivariate analysis, ARF (odds ratio [OR], 54.31; 95% confidence interval [CI], 1.52-1944.00; p = 0.032) and old age (OR, 54.26; 95% CI, 1.52-1932.94; p = 0.028) were independent risk factors for CKD in GUTB patients. CONCLUSIONS: ARF and old age were independent risk factors for CKD in GUTB patients. Therefore, in elderly GUTB patients with ARF at the time of diagnosis, regular follow-up of renal function should be performed even after the end of treatment.

Pregnancy Rates and Outcomes of HIV-Infected Women in Korea.

BACKGROUND: Antepartum, intrapartum, and postpartum preventive measures with antiretroviral drugs, appropriate delivery methods, and discouraging breastfeeding significantly decrease the risk of mother-to-child transmission of human immunodeficiency virus (HIV) infection. Herein, we investigated the pregnancy outcomes in HIV-infected Korean women. METHODS: We retrospectively reviewed medical records of childbearing-age HIV-infected women between January 2005 and June 2017 at four tertiary care hospitals in Korea. RESULTS: Among a total of 95 HIV infected women of child-bearing age with 587.61 years of follow-up duration, 15 HIV-infected women experienced 21 pregnancies and delivered 16 infants. The pregnancy rate was 3.57 per 100 patient-years. Among the 21 pregnancies, five ended with an induced abortion, and 16 with childbirth including two preterm deliveries at 24 and 35 weeks of gestation, respectively. The two preterm infants had low birth weight and one of them died 10 days after delivery due to respiratory failure. Among the 14 full-term infants, one infant was small for gestational age. There were no HIV-infected infants. CONCLUSION: The pregnancy rate of HIV-infected women in Korea is lower than that of the general population. Although several adverse pregnancy outcomes were observed, mother-to-child transmission of HIV infection was successfully prevented with effective preventive measures.

The impact of production of extended-spectrum ß-lactamases on the 28-day mortality rate of patients with Proteus mirabilis bacteremia in Korea.

BACKGROUND: The incidence of Proteus mirabilis antimicrobial resistance, especially that mediated by extended-spectrum ß-lactamases (ESBLs), has increased. We investigated the impact of ESBL production on the mortality of patients with P. mirabilis bacteremia in Korea. METHODS: Patients diagnosed with P. mirabilis bacteremia between November 2005 and December 2013 at a 2000-bed tertiary care center in South Korea were included in this study. Phenotypic and molecular analyses were performed to assess ESBL expression. Characteristics and treatment outcomes were investigated among ESBL-producing and non-ESBL-producing P. mirabilis bacteremia groups. A multivariate analysis of 28-day mortality rates was performed to evaluate the independent impact of ESBLs. RESULTS: Among 62 P. mirabilis isolates from 62 patients, 14 expressed ESBLs (CTX-M, 2; TEM, 5; both, 6; other, 1), and the 28-day mortality rate of the 62 patients was 17.74%. No clinical factor was significantly associated with ESBL production. The 28-day mortality rate in the ESBL-producing group was significantly higher than that in the non-ESBL-producing group (50% vs. 8.3%, p = 0.001). A multivariate analysis showed that ESBL production (odds ratio [OR], 11.53, 95% confidence interval [CI], 2.11-63.05, p = 0.005) was independently associated with the 28-day mortality rate in patients with P. mirabilis bacteremia. CONCLUSIONS: ESBL production is significantly associated with mortality in patients with bacteremia caused by P. mirabilis. Rapid detection of ESBL expression and prompt appropriate antimicrobial therapy are required to reduce mortality caused by P. mirabilis bacteremia.

Metabolic Complications among Korean Patients with HIV Infection: The Korea HIV/AIDS Cohort Study.

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.

HIV migration between blood plasma and cellular subsets before and after HIV therapy.

The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells.

Predictive factors for unfavorable outcomes of tuberculous pericarditis in human immunodeficiency virus-uninfected patients in an intermediate tuberculosis burden country.

BACKGROUND: In areas where Mycobacterium tuberculosis is endemic, tuberculosis is known to be the most common cause of pericarditis. However, the difficulty in diagnosis may lead to late complications such as constrictive pericarditis and increased mortality. Therefore, identification of patients at a high risk for poor prognosis, and prompt initiation of treatment are important in the outcome of TB pericarditis. The aim of this study is to identify the predictive factors for unfavorable outcomes of TB pericarditis in HIV-uninfected persons in an intermediate tuberculosis burden country. METHODS: A retrospective review of 87 cases of TB pericarditis diagnosed at a tertiary referral hospital in South Korea was performed. Clinical characteristics, treatment outcomes, complications during treatment, duration of treatment, and medication history were reviewed. Unfavorable outcome was defined as constrictive pericarditis identified on echocardiography performed 3 to 6 months after initial diagnosis of TB pericarditis, cardiac tamponade requiring emergency pericardiocentesis, or death. Predictive factors for unfavorable outcomes were identified. RESULTS: Of the 87 patients, 44 (50.6%) had unfavorable outcomes; cardiac tamponade (n = 36), constrictive pericarditis (n = 18), and mortality (n = 4). 14 patients experienced both cardiac tamponade and constrictive pericarditis. During a 1 year out-patient clinic follow up, 4 patients required repeat pericardiocentesis and pericardiectomy was performed in 0 patients. In the multivariate analysis, patients with large amounts of pericardial effusion (P = .003), those with hypoalbuminemia (P = .011), and those without cardiovascular disease (P = .011) were found to have a higher risk of unfavorable outcomes. CONCLUSION: HIV-uninfected patients with TB pericarditis are at a higher risk for unfavorable outcomes when presenting with low serum albumin, with large pericardial effusions, and without cardiovascular disease.

Treatment Outcomes of Patients Treated for Pulmonary Tuberculosis after Undergoing Gastrectomy.

Gastrectomy is a proxy of malnutrition, which may lead to increased risk for developing pulmonary tuberculosis (TB). Malabsorption in gastrectomy patients could lead to low serum levels of rifampicin, which may be related to higher treatment failure. However, there is limited information on treatment outcomes of TB in patients who have undergone gastrectomy. This study aims to determine treatment outcomes and adverse effects in patients treated for TB after undergoing gastrectomy for gastric cancer. During the study period, 112 patients were treated for active TB that developed after gastrectomy for gastric cancer. Among them, we selected 15 patients who were culture positive at initial diagnosis and had evidence of active TB on imaging studies; namely, the remaining 97 patients without initial culture or imaging studies were excluded. We thus performed a case-control study of gastric cancer patients treated for TB after undergoing gastrectomy (n = 15). The control group was defined as age- and sex-matched TB patients who had not received gastrectomy (n = 45). Treatment failure in clinical, microbiological aspects, and adverse events were analyzed. Patients who had undergone gastrectomy exhibited higher 4-month clinical failure rates, compared to non-gastrectomy patient: 4 (26.7%) vs. 1 (2.2%), P = 0.012. Gastrointestinal adverse effects were more frequent in patients with gastrectomy, compared to non-gastrectomy patients: 9 (60%) vs. 5 (11.1%), P < 0.001. In conclusion, patients treated for TB after undergoing gastrectomy are associated with higher rates of gastrointestinal adverse events and treatment failure.

Anxiety and depressive symptoms among patients infected with human immunodeficiency virus in South Korea.

Patients infected with human immunodeficiency virus (HIV) may develop mental health problems such as anxiety and depression, which negatively impact of disease progression. We investigated factors associated with the prevalence of anxiety and depression symptoms among HIV-infected patients in Korea. A total of 840 HIV-infected patients who participated in the Korea HIV/AIDS Cohort Study from 2006 to 2012 were evaluated. Socio-demographic, epidemiologic, and clinical variables were obtained through standardized questionnaires. The State-Trait Anxiety Inventory and Beck Depression Inventory were used to assess the symptoms of anxiety and depression. Multiple logistic regression analyses were performed to identify factors associated with symptoms of anxiety and depression. The prevalence of anxiety and depressive symptoms among HIV-infected patients was 32% and 36%, respectively. Ex-smoker and persistent symptoms for more than one week within the past six months and diagnosis of HIV infection within one year were associated with increased anxiety symptoms (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.09-2.69; OR 1.52, 95% CI 1.09-2.11; OR 1.49, 95% CI 1.02-2.20) and current smoking and persistent symptoms were also associated with increased depressive symptoms (OR 2.10, 95% CI 1.31-3.30; OR 1.87, 95% CI 1.25-2.79). Marital status, current smoking, current drinking, and persistent symptoms were associated with both increased anxiety and depressive symptoms (OR 1.75, 95% CI 1.07-2.88; OR 1.66, 95% CI 1.06-2.61; OR 1.88, 95% CI 1.18-2.99). The prevalence of anxiety and depressive symptoms among HIV-infected patients is higher than those estimated for the general population. This study shows the necessity to evaluate symptoms of anxiety and depression and suggest psychological support for HIV-infected patients who smoke or have persistent symptoms or have sexual partner or drink.

A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean patient successfully treated with clarithromycin.

BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of diffuse interstitial lung disease characterized by the pathology of fibroblastic plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli. The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients has rarely been described, and there have been no clinical case reports in Korea. CASE PRESENTATION: A 24-year-old female who had been diagnosed with HIV ten years prior was admitted due to a 1-year history of cough and sputum production and a 3-day history of fever. She had poor adherence to anti-retroviral therapy (ART) due to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was 5 cells/mm(3). A high resolution computed tomography (CT) scan showed tiny centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely considering the rapid radiologic improvement and negative tuberculosis PCR results. Due to the unknown etiology, we performed video-assisted thoracoscopic surgery (VATS) to determine the cause of the diffuse lung infiltration. Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication and intravenous ceftriaxone were discontinued, while treatment with clarithromycin monotherapy was sustained. Five months after discharge, the patient was asymptomatic with a normal chest x-ray and as her adherence to ART improved, her CD4 T-cell count rose to 181 cells/mm(3). Clarithromycin was discontinued at that time and the patient is currently receiving regular outpatient follow-up. CONCLUSION: This case suggests that macrolides are a potential treatment option in HIV-infected patients with mild BOOP. In cases that are otherwise unexplained or unresponsive to treatment, BOOP should be taken into consideration and surgical biopsy performed to confirm a diagnosis of BOOP.

Incidence and risk factors for carbapenem- and multidrug-resistant Acinetobacter baumannii bacteremia in hematopoietic stem cell transplantation recipients.

BACKGROUND: Bacteremia with multidrug-resistant (MDR) Acinetobacter baumannii with carbapenem resistance is an important healthcare-associated infection that increases morbidity and mortality in immunocompromised patients. The aim of this study was to assess the annual incidence and clinical characteristics of such bacteremia and to identify the risk factors for infection in hematopoietic stem cell transplantation (HSCT) recipients. METHODS: A retrospective cohort and case-control study was conducted in 483 HSCT recipients between January 2005 and December 2011 at a single tertiary center. Thirty-eight control HSCT patients without evidence of post-transplant infection were matched with 19 patients with bacteremia due to MDR A. baumannii in a 2:1 ratio. RESULTS: The total incidence of carbapenem-resistant-MDR A. baumannii bacteremia was 0.52 cases/10,000 patient-days. In most cases (17 of 19, 89.5%), bacteremia developed after engraftment. Pneumonia was the origin of bacteremia in all patients. Eighteen (94.7%) patients with bacteremia and 3 (8.3%) without bacteremia died. In multivariate regression analyses, the duration between admission and HSCT (odds ratio (OR) 2.19 per 1-day increase, p = 0.030) and a history of care in an intensive care unit after HSCT (OR 32.2, p = 0.021) were independent risk factors for the development of carbapenem-resistant-MDR A. baumannii bacteremia. CONCLUSIONS: We report that carbapenem-resistant-MDR A. baumannii bacteremia in HSCT recipients is a fatal infectious complication and mainly develops after engraftment.

Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection in Seoul, South Korea.

BACKGROUND: There have been various efforts to identify less costly but still accurate methods for monitoring the response to HIV treatment. We evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Seoul, South Korea. METHODS: We conducted the first prospective study of pooled nucleic acid testing (NAT) using a 5 minipool + algorithm strategy versus individual viral load testing for patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. The viral load assay used has a lower level of detection of 20 HIV RNA copies/ml, and the cost per assay is US$ 136. The 5 minipool +algorithm strategy was applied and 43 pooled samples were evaluated. The relative efficiency and accuracy of the pooled NAT were compared with those of individual testing. RESULTS: Using the individual viral load assay, 15 of 215 (7%) plasma samples had more than 200 HIV RNA copies/ml. The pooled NAT using the 5 minipool + algorithm strategy was applied to 43 pooled samples; 111 tests were needed to test all samples when virologic failure was defined at HIV RNA ≥ 200 copies/ml. Therefore, 104 tests were saved over individual testing, with a relative efficiency of 0.48. When evaluating costs, a total of US$ 14,144 was saved for 215 individual samples during 10 months. The negative predictive value was 99.5% for all samples with HIV RNA ≥ 200 copies/ml. CONCLUSIONS: The pooled NAT with 5 minipool + algorithm strategy seems to be a very promising approach to effectively monitor patients receiving ART and to save resources.

Anti-vascular endothelial growth factor antibody attenuates inflammation and decreases mortality in an experimental model of severe sepsis.

INTRODUCTION: Severe sepsis is associated with an unacceptably high rate of mortality. Recent studies revealed elevated levels of vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, in patients with sepsis. There was also an association between VEGF levels and sepsis severity. Here we investigate the effects of an anti-VEGF antibody (Bevacizumab, Bev) in an experimental model of sepsis. METHODS: Human umbilical vein endothelial cells (HUVECs), murine cecal ligation and puncture (CLP), and endotoxemia models of sepsis were used. HUVECs were treated with lipopolysaccharide (LPS) and/or Bev, harvested and cytokine mRNA levels determined using a semi-quantitative reverse transcription-polymerase chain reaction assay. The levels of inflammatory cytokine were also determined in HUVECs supernatants. In addition, the effects of Bev on mortality in the CLP and endotoxemia models of sepsis were evaluated. RESULTS: Treatment with Bev and LPS significantly decreased the expression and the level of inflammatory cytokines in HUVECs relative to LPS alone. In CLP and endotoxemia models, survival benefits were evident in mice given 0.1 mg/kg of Bev relative to the CLP or LPS alone (P<0.001 and P=0.028, respectively), and in 6 h post-treated mice relative to the CLP alone for the effect of different time of Bev (P=0.033). In addition, Bev treatment inhibited LPS-induced vascular leak in the lung, spleen and kidney in the murine endotoxemia model (P<0.05). CONCLUSIONS: Anti-VEGF antibody may be a promising therapeutic agent due to its beneficial effects on the survival of sepsis by decreasing inflammatory responses and endothelial permeability.

A comparison of the predicted risk for cardiovascular disease between HIV-infected and uninfected persons in Korea.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has extended the life expectancy of persons infected with the human immunodeficiency virus type 1 (HIV-1). However, cardiovascular disease (CVD) is currently an increasing concern for HIV-infected persons. METHODS: We conducted a cross-sectional case-control study to evaluate and compare the 10-y cardiovascular risk of HIV-infected Koreans who had been receiving HAART for over 6 months and age- and sex-matched uninfected persons who visited a health promotion center, by calculating Framingham risk scores (FRS). RESULTS: The average 10-y risk for cardiovascular events (FRS) was 7.07% (2-45) in the HIV group and 6.87% (1-37) in the control group (p = 0.77), corresponding to the very low risk group. Among HIV patients, the FRS was above 10% (low to moderate cardiovascular risk) in 19.9% of the patients, and above 20% (high risk) in 1.7% of the patients. In the healthy control group, the FRS was above 10% in 16.8% and above 20% in 2.7% (p = 0.57). The FRS was not significantly different for HIV-infected patients treated with protease inhibitor (PI)-based HAART and those treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART (7.26 ± 6.3 and 6.81 ± 4.4, respectively, p = 0.69). CONCLUSIONS: The predicted cardiovascular risk of HIV-infected Koreans on HAART by FRS equation was low and similar to that of age- and sex-matched healthy control persons. However, the possibility remains that actual cardiovascular events could be underestimated. The next step for predicting the cardiovascular risk is to calculate the Data Collection of Adverse Events of Anti-HIV Drugs (D:A:D) equation risks.

Red blood cell transfusions are associated with lower mortality in patients with severe sepsis and septic shock: a propensity-matched analysis*.

OBJECTIVES: To evaluate the effects of transfusions in patients with severe sepsis and septic shock on mortality. DESIGN: Propensity-matched analysis of a prospective observational database (April 2005 to February 2009). SETTING: Twenty-two medical and surgical intensive care units in 12 teaching hospitals in Korea. PATIENTS: One thousand fifty-four patients with community-acquired severe sepsis and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,054 patients, 407 (38.6%) received a blood transfusion. The mean pretransfusion hemoglobin level was 7.7 ± 1.2 g/dL. Transfused patients had higher 28-day and in-hospital mortality rates (32.7% vs. 17.3%; p < .001, 41.3% vs. 20.3%; p < .001, respectively) and a longer duration of hospital stay (21 [interquartile range, 10-35] vs. 13 [interquartile range, 8-24] days; p < .001), but were more severely ill at admission (lower systolic blood pressure, higher Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score at admission). In 152 pairs matched according to the propensity score depending on patient transfusion status, transfused patients had a lower risk of 7-day (9.2% vs. 27.0%; p < .001), 28-day (24.3% vs. 38.8%; p = .007), and in-hospital mortality rates (31.6% vs. 42.8%; p = .044). After adjusting for blood transfusion as a time-dependent variable in multivariable analysis, blood transfusion was independently associated with lower risk of 7-day (hazard ratio 0.42, 95% confidence interval 0.19-0.50, p = .026), 28-day (hazard ratio 0.43, 95% confidence interval 0.29-0.62, p < .001), and in-hospital mortality (hazard ratio 0.51, 95% confidence interval 0.39-0.69, p < .001). CONCLUSIONS: In this observational study of patients with community-acquired severe sepsis and septic shock, red blood cell transfusions were associated with lower risk of mortality.