Factors Associated with Treatment Satisfaction Among People Living with HIV in Japan and Other Selected Countries: Examination of the Intertwined Roles of Medication, Patient, and Provider Characteristics.

We examined satisfaction and perceived challenges with antiretroviral therapy (ART) among people living with HIV (PLHIV) in Japan vs three other Asian countries (China, Taiwan, South Korea), and 21 non-Asian countries, using data from the 2019 Positive Perspectives Study (pooled sample size from all 25 countries = 2389). Participants in other Asian countries were more likely than those in Japan to report they missed ART ≥ 1 time in the past month because they were depressed/overwhelmed (57.4%[89/155] vs 32.0%[24/75]), had privacy concerns (56.8%[88/155] vs 30.7%[23/75]), were concerned about the potential long-term negative impacts of ART (46.5%[72/155] vs 26.7%[20/75]), or just wanted to forget about HIV (45.8%[71/155] vs 22.7%[17/75]). ART satisfaction however did not differ significantly between surveyed PLHIV in Japan (54.7%[41/75]) vs those in other Asian countries (47.7%[74/155]). The percentage who felt that daily ART dosing limited their lives was 36.0%[27/75] among participants from Japan, 48.4%[75/155] among participants from other Asian countries, and 27.3%[589/2159] among those from non-Asian countries. Within a structural equation model using pooled data from all 25 countries, positive correlations were seen between ART satisfaction and "provider engagement" (ß = 0.35), high perceived control over ART dosing schedule (ß = 0.28), and the belief that ART prevents HIV transmission (ß = 0.16). Conversely, negative correlations were seen between ART satisfaction and experience of ART side-effects (ß = - 0.24), high "ART anxiety" (ß = - 0.20); and being on multi-tablet regimens (ß = - 0.13). Those ART-satisfied reported higher self-rated health and greater ART adherence. These findings underscore the need for patient-centered care to enhance treatment satisfaction and improve ART adherence.

Safety and Effectiveness Analysis of Dolutegravir in Patients with HIV-1: Interim Report of Post-Marketing Surveillance in Japan.

INTRODUCTION: Dolutegravir (DTG), a novel HIV-integrase strand transfer inhibitor (INSTI), is usually used with multiple antiretrovirals (ARVs) for treatment of HIV. DTG is now approved as Tivicay tablets in over 120 countries and Triumeq combination tablets (DTG/abacavir [ABC]/lamivudine [3TC]) in over 90 countries. In Japan, these formulations have been marketed since 2014 and 2015. The post-marketing prospective surveillance has been conducted as part of the HIV-Related Drug (HRD) cooperative survey aimed to collect actual drug use information in all of these DTG-treated patients in accordance with conditions for initial approvals. METHODS: The survey has been conducted to evaluate long-term safety and effectiveness of DTG since 2014, for approximately 6 years. The safety was evaluated by incidence of adverse drug reactions (ADRs) and change in body weight. The effectiveness was evaluated by plasma HIV RNA copies/mL and peripheral CD4+ cell counts. RESULTS: Of 2292 patients in 30 Japanese sites, 565 (24.65%) reported ADRs. The most common ADR was blood creatinine increased (4.28%). Incidence of ADRs was statistically significantly higher in patients with severe symptoms (Centers for Disease Control and Prevention [CDC] categories B and C) than those with category A, and in patients with comorbidities than those without comorbidities. Whereas incidence of ADRs was statistically significantly lower in antiretroviral therapy (ART)-experienced patients than that in ART-naïve patients. Incidence of ADRs related to suicide or self-injurious behavior was statistically significantly higher in patients with comorbidities of psychiatric disorders than those without comorbidities. The body weight tended to increase over time and those changes and percentage changes from baseline were greater in ART-naïve patients compared with ART-experienced patients. HIV RNA copies/mL and CD4+ cell counts showed favorable shifts from baseline in both ART-naïve and ART-experienced patients. CONCLUSION: The results of the survey identified no new safety and effectiveness risks in Japanese patients with HIV/AIDS treated with DTG.

Magnetic resonance imaging changes in Asian people living with HIV.

BACKGROUND: Previous studies have reported a significant increase in age-related magnetic resonance imaging (MRI) changes in relatively younger people living with HIV (PLWH). However, there is little data available for brain changes in Asian PLWH. The data to differentiate HIV specific brain change from usual aging change was also sparse. To clarify them, we assessed the presence of leukoaraiosis and brain atrophic changes on MRI in young and middle-aged Japanese PLWH. METHODS: We reviewed data from well-controlled PLWH (age: 20-64 years) and coeval controls. We evaluated the presence of leukoaraiosis, as well as the extent of whole-brain grey matter (GM) atrophy and parahippocampal atrophy on brain MRI and determined between-group differences. Moreover, we evaluated the severity of parahippocampal atrophy based on the voxel-based specific regional analysis system for Alzheimer's disease. RESULTS: We enrolled 40 PLWH and 33 controls (median age: 40.15 and 48.00 years, respectively, [p = .3585]). Leukoaraiosis was significantly more prevalent among the PLWH (20 cases [50%]) than in the controls (9 cases [27.3%]) (univariate: p = .0483, multivariate: p = .0206). The extent of whole-brain GM atrophy was significantly greater in the PLWH than in the controls (univariate: p < .001, multivariate: p = .0012). Contrastingly, there was no significant between-group difference in the extent and severity of parahippocampal atrophy. CONCLUSIONS: Aging changes in the brain were significantly more prevalent in well-controlled Japanese PLWH. However, the process of atrophic brain changes might differ between HIV and one of age-related diseases, Alzheimer's disease.

Prevalence of and Risk Factors for Low Free Testosterone Levels in Japanese Men with Well-controlled Human Immunodeficiency Virus Infection.

BACKGROUND: The change in the prevalence of hypogonadism with age in men with human immunodeficiency virus (HIV) infection is subject to debate. OBJECTIVE: To address this issue, we diagnosed hypogonadism based on serum levels of free testosterone (fTST) rather than total testosterone which is thought to be an inaccurate indicator. We also determined the relationship between age and fTST levels and identified risk factors for hypogonadism in men with HIV infection. METHODS: We retrospectively reviewed fTST levels and associated clinical factors in 71 wellcontrolled HIV-infected men who were treated at Teikyo University Hospital between April 2015 and March 2016 and who had data available on serum fTST levels, measured >6 months after starting antiretroviral therapy. fTST was measured using radioimmunoassay on blood samples collected in the morning. Risk factors for hypogonadism were identified using Welch's t-test and multiple regression analysis. RESULTS: The men had a mean (± standard deviation) age of 47.4 ± 13.6 years, and mean (± standard deviation) serum fTST level of 13.0 ± 6.1 pg/mL. Fifteen (21.1%) men had hypogonadism based on a fTST <8.5 pg/mL. Serum fTST levels significantly decreased with age (-0.216 pg/mL/year). Older age and low hemoglobin levels were identified as risk factors for hypogonadism. CONCLUSION: The men in the study experienced a more rapid decline in fTST levels with age than men in the general population (-0.161 pg/mL/year). Serum fTST levels in men with HIV infection should be monitored, especially in older men and those with low hemoglobin levels.

Cerebral blood flow in young and middle-aged people living with HIV.

Purpose: Neurocognitive disorder has been noted as a long-term complication in individuals with HIV. In people living with HIV, regardless of treatment, age-related changes like arteriosclerosis are well-known to be accelerated. Such accelerated aging changes may decrease cerebral blood flow in younger generations with HIV, increasing the rate of occurrence of neurocognitive disorders. We investigated regional cerebral blood flows in well-controlled Japanese people living with HIV under 65 years old to clarify whether age-related changes in regional cerebral blood flows are accelerated in people living with HIV.Method: Japanese male HIV patients >20 years old but <65 years old who visited Teikyo University Hospital between August 2013 and September 2015 were recruited to and enrolled in this study. Healthy coeval male volunteers during the same period were recruited as controls. Magnetic resonance imaging was performed. Twelve regional cerebral blood flows were calculated from pseudocontinuous arterial spine labelling data.Results: Participants in this study comprised 40 individuals with HIV (HIV-positive group) and 33 non-HIV individuals (Control group). Median age was 40.15 years [interquartile range (IQR), 32.80-50.55 years] for the HIV-positive group and 48.00 years [IQR, 37.75-59.25 years; p = 0.3585] for the Control group. No significant differences in regional cerebral blood flows were seen between groups. In the HIV-positive group, cerebral blood flows decreased with age in the neocortex, although no significant decrease was observed in any of the regions in the control group.Conclusions: Significant age-related declines in cerebral blood flows in the neocortex may occur earlier in HIV patients.

Safety analysis of Lexiva tablets 700 (fosamprenavir calcium hydrate) in post-marketing surveillance in Japan.

Objective: Fosamprenavir, a protease inhibitor (PI) to treat human immunodeficiency virus (HIV)-infected patients, has been approved in more than 40 countries and mainly used with nucleoside reverse transcriptase inhibitors. In Japan, Lexiva tablet (fosamprenavir calcium hydrate) has been marketed since January 2005 and used in clinical practice. The safety and effectiveness of fosamprenavir in HIV-infected Japanese patients were evaluated in an observational surveillance study (OTH112334).Methods: A post-marketing surveillance study (PMS) of fosamprenavir usage in HIV-infected Japanese subjects evaluating drug safety was conducted under Good Post-marketing Study Practice from January 2005 to December 2014.Results: Of 364 patients receiving fosamprenavir, 51% received emtricitabine/tenofovir disoproxil fumarate. Adverse events whose causal relationship could not be completely ruled out (adverse drug reactions; ADRs) were reported in 43.7%; the most common were diarrhoea (10.4%), hyperlipidaemia (8.5%) and hypertriglyceridaemia (6.9%). Serious ADRs were reported in 26 patients (32 events), including 1 death attributed to hepatic failure. Most ADRs occurred within 180 days after fosamprenavir was started. ADRs were more frequent in patients with the Centers for Disease Control and Prevention category B (AIDS or lipid disorders) or in those taking fosamprenavir combined with abacavir and lamivudine. Although spontaneous bleeding has been reported in hemophiliac patients taking other PIs, in this survey, only one muscle haemorrhage case was reported in 24 hemophiliac patients.Conclusions: The results of this PMS analysis in Japan support its known safety profile and identified no new safety risks for people living with HIV/AIDS in Japan currently on, or beginning treatment with, fosamprenavir.

The prevalence of low serum free testosterone and the short-term effect of anti-retroviral therapy in male Japanese treatment-naïve HIV patients.

OBJECTIVES: The prevalence of hypogonadism in HIV patients is still a matter of debate. Today, serum free testosterone (fTST) is thought to be more important than serum testosterone in the diagnosis of hypogonadism in patients with HIV. This study aimed to determine the prevalence of low fTST levels and the effects of anti-retroviral therapy (ART) on fTST levels in treatment-naïve male Japanese patients with HIV. METHODS: Patients who visited Teikyo University Hospital, Japan between 2010 and 2016 were enrolled. Patients' fTST levels were evaluated twice with a radioimmunoassay in the morning, at the onset of ART and one year later. Clinical factors were also reviewed. The patients were divided into two groups ('hypogonadism' and 'normal') based on Japanese criteria. To determine factors related to low fTST in treatment-naïve patients, the Mann-Whitney U test and a multiple-regression analysis were used. Changes in fTST levels after ART initiation were evaluated with a paired t-test. RESULTS: Data from 25 patients were collected. Their median age was 36.0 years, and the median fTST level was 8.00 pg/ml in the treatment-naïve state. Thirteen patients (52%) were in the hypogonadism group. Low levels of fibroblast growth factor 23 were significantly related to low fTST levels. After the start of ART, fTST levels increased significantly (median 8.00 interquartile range [6.40-9.70] to 9.60 [7.60-13.10] pg/ml, p = 0.0081). CONCLUSIONS: Subnormal fTST levels occurred frequently among the present study patients in treatment-naïve settings. Free testosterone levels in patients with HIV were significantly increased one year after the start of ART.

Inhibition of osteoblast differentiation by ritonavir.

Osteoporosis is one of the chronic complications seen in human immunodeficiency virus (HIV)-infected patients, and affects patients at high prevalence. The causes of osteoporosis in HIV-infected patients are multiple, and include chronic HIV infection, living habits such as smoking and alcohol consumption, and antiretroviral drug use. Among antiretroviral drugs, protease inhibitors have been reported to be associated with osteoporosis. However, it remains to be determined how anti-HIV drugs affect osteoblast differentiation. In the current study, MC3T3-E1 cells, a mouse osteoblastic cell line, were cultured in osteoblast differentiation medium with or without different protease inhibitors (ritonavir, lopinavir, darunavir or atazanavir), and alkaline phosphatase (ALP) activity and the expression of Runt-related transcription factor 2 (Runx2) were analyzed. The ALP activity in MC3T3-E1 cells cultured with ritonavir was significantly reduced compared with that in cells in only osteoblast inducer reagent, indicating that ritonavir inhibited osteoblast differentiation. Meanwhile, ALP activity was not reduced in cells cultured with any of the other inhibitors. In addition, ritonavir inhibited the expression of Runx2, a key regulator of osteoblast differentiation, in the early period of osteoblast differentiation. To the best of our knowledge, this is the first study to demonstrate that ritonavir inhibits osteoblast differentiation in vitro. The present findings may explain the mechanism of osteopenia induced by combination antiretroviral therapy involving protease inhibitors.

Short Communication: The Clinical Value of Cystatin C as a Marker of Renal Function in HIV Patients Receiving Dolutegravir.

Dolutegravir (DTG) is an integrase strand transfer inhibitor that is used for the treatment of HIV infection. DTG inhibits organic cation transporter 2 on the basolateral side of proximal tubule cells of the kidney and leads to increased serum creatinine levels without true renal function deterioration. In HIV patients who receive DTG, an alternative test to serum creatinine measurement is needed to determine the correct renal function. We retrospectively evaluated 18 HIV-infected men who had received combination antiretroviral therapy (cART), including DTG, and who had available data on serum creatinine and cystatin C levels. We used paired t-test to assess the changes in estimated glomerular filtration rate (eGFR) calculated by serum creatinine or cystatin C level, after the start of cART. In all 18 patients, only 2 cases were naive, whereas 16 cases switched treatment. Based on serum creatinine level, eGFR significantly changed from 67.9 (61.2-95.7) ml/min per 1.73 m2 [medians and interquartile ranges ] to 63.6 (55.5-83.7) ml/min per 1.73 m2 (p = .0004). Conversely, eGFR was almost unchanged [79.8 (77.7-82.5) to 80.0 (77.1-82.5) ml/min per 1.73 m2; p = .132] when serum cystatin C level was used for estimation. In HIV patients receiving DTG, measurement of serum cystatin C as an alternative renal function test might be clinically valuable because it is not affected by DTG administration.

Co-Colonization with Neisseria species Is a Risk Factor for Prolonged Colonization with Multidrug-Resistant Acinetobacter baumannii in the Respiratory Tract.

Multidrug-resistant Acinetobacter baumannii (MDRAB) colonization increases the risk of bacterial spread in the hospital setting. The impact of clinical factors, including antibiotic use, on prolongation of MDRAB colonization has not been investigated. Patients with respiratory tract MDRAB detected using culture were enrolled in this study. Long-term colonizers and short-term colonizers were defined as patients whose colonization periods were >30 days or ≤30 days, respectively. Clinical data were abstracted from medical records. MDRAB was isolated in 34 patients. There were 13 long-term colonizers and 9 short-term colonizers. Twelve patients were lost to follow-up and excluded from the study. There were no significant differences in average leukocyte counts, numbers of antibiotic classes administered, duration of antibiotic use in the 30 days following colonization, or rates of central catheterization or mechanical ventilation between the 2 groups. Long-term colonizers carried Neisseria species (spp.) more frequently in the 30 days following colonization than short-term colonizers (7/13 vs 1/9, p = 0.01); however, this was not the case prior to colonization with MDRAB (5/13 vs 1/9, p = 0.33). The 90-day MDRAB colonization rates for Neisseria-negative patients and Neisseria-positive patients were 10.0% and 83.3%, respectively (P < 0.01). Prolonged MDRAB colonization in the respiratory tract was associated with Neisseria spp. co-colonization.

Decreased serum bone specific alkaline phosphatase and increased urinary N-terminal telopeptide of type I collagen as prognostic markers for bone mineral density loss in HIV patients on cART.

OBJECTIVES: Bone mineral density (BMD) loss is a major chronic complication in HIV patients. We performed a prospective study to determine the time course of BMD changes and to find prognostic factors of BMD loss in HIV patients on combination antiretroviral therapy (cART). PATIENTS AND METHODS: Subjects were 54 male Japanese HIV patients who had been on cART ≥1 year with no therapeutic agents for osteoporosis. Patients were observed for ≥1 year (median 3.1 years) and underwent annual BMD analyses using dual energy X-ray absorptiometry. Changes in BMD at lumbar spine and femoral neck were calculated for each person-year of all the patients. Clinical factors were also collected simultaneously with BMD examinations to determine prognostic factors for BMD loss. RESULTS: In total, 173 person-years in 54 patients were observed. One third (19, 35.2%) and slightly over half (30, 55.6%) patients showed BMD decreases at lumbar spine and femoral neck, respectively. However, the median BMD changes at lumbar spine and femoral neck were 0.0% and -0.52% per year, respectively. Monovariant and mixed model analyses determined that decreased serum bone specific alkaline phosphatase (BAP, p = 0.0047) and increased urinary N-terminal telopeptide (uNTx, p = 0.0011) were prognostic factors for BMD loss at lumbar spine and femoral neck, respectively. CONCLUSIONS: BMD at both lumbar spine and femoral neck changed little on average in HIV patients on cART. Decreased serum BAP or increased uNTx may be helpful to predict progressive BMD loss in the following year and to select patients for BMD follow-up or initiation of anti-osteoporosis treatment.

Increase of 25-hydroxyvitamin D levels after initiation of combination antiretroviral therapy.

Although vitamin D deficiency in HIV patients reported worldwide, the mechanisms and the effect of combination antiretroviral therapy (cART) on vitamin D levels are unclear. Patients were 50 male Japanese with HIV who visited Teikyo University Hospital, Tokyo, Japan. Patients were divided into those receiving cART (cART-experienced group, n = 30) and those who had not received cART (cART-naïve group, n = 20). Patients in the cART-experienced group had received treatment with cART for more than one year and those in the cART-naïve group were just about to start cART at study entry. Patients underwent measurement of serum 25-hydroxyvitamin D (25(OH)D) levels and assessment of clinical factors twice at one year intervals. At study entry, 23 (76.7%) in the cART-experienced group and 19 (95.0%) in the cART-naïve group had vitamin D insufficiency or deficiency. Mean 25(OH)D values were significantly higher in the cART-experienced group (25.2 ng/ml vs. 19.3 ng/ml, p = 0.01). However, levels of 25(OH)D at one year increased more in the cART-naïve group (-1.1 ng/ml vs. 5.0 ng/ml, p = 0.01), with mean 25(OH)D values in the cART-naïve group increasing to match those in the cART-experienced group. HIV infected patients who initiated cART showed increases in vitamin D levels in one year.

Characteristics of serum endocan levels in infection.

OBJECTIVES: Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels during infection and their associations with other clinical factors. The aim of this study was to assess the time course of endocan levels and the associations of endocan with clinical factors during infection by comparison with other biomarkers. METHODS: Serum samples and blood cultures were obtained from patients who were diagnosed with infection from June 2013 to March 2014. Serum endocan, C-reactive protein (CRP), and procalcitonin (PCT) levels during four periods during infection were measured (day 0, day 1-2, day 3-5, and day 6-10). RESULTS: A total of 78 patients were enrolled in this study. The median endocan level decreased by only 23% during infection, whereas both serum CRP and PCT levels decreased by more than 80%. Endocan levels were correlated to neither CRP levels nor PCT levels in each period. Endocan levels at day 0 in patients with bacteremia were higher than those without bacteremia (1.09 ng/mL vs 0.82 ng/mL, P=0.002), but neither CRP levels nor PCT levels at day 0 were different between the two groups. Areas under the receiver operator characteristic (ROC) curves of endocan, CRP, and PCT at day 0 were 0.662, 0.343, and 0.563, respectively. Positive blood cultures tended to be related to high endocan levels, but not significantly (odds ratio: 4.24, 95% CI: 0.99-10.34, P=0.05). CONCLUSIONS: In bacteremic cases, serum endocan levels in bacteremia tended to be higher than in non-bacteremic cases. Although endocan level was not identified as a prognostic factor of bacteremia, further prospective study concerning the relationship between serum endocan level and bacteremia would be needed.

Hyaluronic Acid concentration in pleural fluid: diagnostic aid for tuberculous pleurisy.

BACKGROUND: A high concentration of hyaluronic acid in pleural fluid is suggestive of malignant mesothelioma. However, a relatively high concentration of hyaluronic acid was also seen in the pleural fluid of patients with benign inflammatory diseases. To show the utility of measuring hyaluronic acid levels in pleural fluid to diagnose tuberculous pleurisy, we compared the clinical features and levels of hyaluronic acid in the pleural fluid of patients with and without tuberculous pleurisy. METHODS: We enrolled 27 patients with infective pleurisy admitted at Teikyo University Hospital from January 2010 to December 2013. Ten patients were diagnosed with tuberculous pleurisy, and 17 with non-tuberculous pleurisy. We reviewed the clinical features and data of all 27 patients and compared the two groups. We analyzed and compared the concentration of hyaluronic acid and adenosine deaminase in their pleural fluid. RESULTS: Patients with tuberculous pleurisy tended to have significantly higher concentrations of hyaluronic acid and adenosine deaminase in their pleural fluid (tuberculous pleurisy patients vs. other infective pleurisy patients: hyaluronic acid (× 10(3) ng/mL); 42.9 ± 23.3 vs. 16.8 ± 17.9, P = 0.003, adenosine deaminase (IU/L); 89.7 ± 33.3 vs. 74.0 ± 90.9, P = 0.032). Receiver operating characteristic analysis revealed no significant difference in the area under the curve of hyaluronic acid and adenosine deaminase volumes in pleural fluid, suggesting their equivalent value as major diagnostic tools for tuberculosis pleurisy. CONCLUSIONS: Hyaluronic acid concentration in pleural fluid can be a valuable tool for the diagnosis of tuberculous pleurisy.

Clinical efficacy of peramivir in adult patients with seasonal influenza during the winter of 2012 in Japan.

BACKGROUND: Peramivir is an intravenously administered neuraminidase inhibitor for influenza. The clinical efficacy of peramivir remains unclear because it is used in a limited number of countries. We compared the clinical efficacy of peramivir with that of oseltamivir in influenza patients during the 2012-2013 season. METHODS: Thirty-two influenza patients who were hospitalized at Teikyo University Hospital, a teaching hospital in Tokyo, Japan, from October 2012 to March 2013 were enrolled. Among them, 23 and 9 were treated with peramivir and oseltamivir, respectively. The end points of this study were the time to defervescence and survival rate. RESULTS: There were no significant differences in the clinical backgrounds of the two groups. However, patients treated with peramivir tended to have a higher incidence of consciousness disturbance [34.8% (8/23) vs 0.00% (0/9), P = 0.064]. There were no significant differences between the peramivir and oseltamivir groups with respect to the time to defervescence (30.9 ± 18.7 h vs 34.7 ± 18.6 h) or survival rate [95.7% (22/23) vs 100% (9/9), respectively]. CONCLUSIONS: The clinical efficacy of peramivir is non-inferior to that of oseltamivir, although peramivir tended to be used in patients with serious complications. Intravenous administration of peramivir may be useful for patients with serious complications, such as consciousness disturbances.

Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins.

We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of ß-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours.

Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B expression.

Treatment with antiretroviral therapy, including protease inhibitors (PIs), may result in metabolic side-effects, for example insulin resistance. The aim of the present study was to investigate the mechanism of the dysregulation of insulin signaling by two PIs, lopinavir and darunavir, by analyzing changes in the expression or activity of proteins associated with insulin signaling. 3T3-L1 preadipocytes were pretreated with lopinavir or darunavir for 48 h and then stimulated with insulin for 30 min. The cell lysates were subjected to western blotting with anti-phospho-insulin receptor substrate (IRS) 1, anti-IRS1, anti-suppressor of cytokine signaling (SOCS) 1, anti-SOCS3 and anti-protein tyrosine phosphatase (PTP) 1B antibodies and to immunoprecipitation with anti-IRS1 antibody. Translocation of glucose transporter 4 (GLUT4) following treatment with lopinavir or darunavir was observed using immunofluorescence. While GLUT4 was recruited to the cellular membrane in control adipocytes following insulin stimulation, it was diffusely distributed in the cytosol in lopinavir-treated adipocytes. In darunavir-treated adipocytes, GLUT4 was mainly recruited to the cellular membrane, but some GLUT4 remained in the cytosol. After insulin stimulation, IRS1 was tyrosine-phosphorylated to a greater extent in control adipocytes compared with darunavir-treated adipocytes. Tyrosine phosphorylation of IRS1 was inhibited in lopinavir-treated adipocytes. The expression of PTP1B was upregulated in adipocytes pretreated with the PIs, particularly lopinavir, compared with those pretreated with a vehicle control. The degree of regulation in insulin signaling differs between lopinavir and darunavir. One mechanism by which lopinavir regulates insulin signaling is by the promotion of PTP1B expression.

Multifocal Cellulitis due to Disseminated Neisseria Gonorrhoeae in a Male Patient.

We report a rare case of disseminated gonococcal infection in a 37-year-old man presenting with multifocal cellulitis. The patient presented with fever and painful swelling of the right foot and left hand, and was admitted to our hospital. CT scanning of the extremities revealed multifocal cellulitis. Transthoracic echocardiography findings were normal, and piperacilin/tazoactam therapy was initiated. On antibiotic day 4, Neisseria gonorrhoeae was cultured from a purulent effusion collected from a focal site. Chlamydia trachomatis was detected in urine samples by PCR. We made the diagnosis of multifocal cellulitis due to N. gonorrhoeae in a patient with chlamydia urethritis. The antibiotic agent was changed from piperacilin/tazobactam to ceftriaxone. Levofloxacin was also administered for chlamydia urethritis. By admission day 14, all lesions had resolved and administration of antibiotic agents was terminated. Disseminated gonococcal infection, although rare, should be included in the differential diagnosis of all sexually active patients who present with multifocal cellulitis - also a rare condition, particularly in light of the fact that in recent times, patterns of sexual activity have changed, which was a pertinent factor in this case.