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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" (β = 0.35), high perceived control over ART dosing schedule (β = 0.28), and the belief that ART prevents HIV transmission (β = 0.16). Conversely, negative correlations were seen between ART satisfaction and experience of ART side-effects (β = - 0.24), high "ART anxiety" (β = - 0.20); and being on multi-tablet regimens (β = - 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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

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.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (© 2014 John Wiley & Sons Ltd.)

The emergence and transmission of drug-resistant human immunodeficiency virus-1 (HIV-1) compromises antiretroviral treatment for HIV-1. Thus, testing for drug resistance is recommended at diagnosis and before initiating highly active antiretroviral treatment. We conducted an epidemiological study enrolling newly diagnosed patients between 2003 and 2008 in our nationwide surveillance network. In the 6-year study period, the prevalence of drug-resistant HIV-1 among 2573 patients, consisting mainly of Japanese men in their late-30s and infected through male-to-male sexual contacts, followed an increasing trend from 5.9% (16/273) in 2003 to 8.3% (50/605) in 2008. Nucleoside reverse transcriptase inhibitor-associated mutations predominated in each year, with T215 revertants being the most abundant. The predictive factor for drug-resistant HIV-1 transmission was subtype B (OR=2.36; p=0.004), and those for recent HIV-1 infection were male gender (OR=3.79; p=0.009), MSM behavior (OR=1.67; p=0.01), Japanese nationality (OR=2.31; p=0.008), and subtype B (OR=5.64; p<0.05). Continued activities are needed to raise awareness of the risks of HIV-1 infection and complications of drug-resistant strains. Continued surveillance is also needed to understand trends in the HIV-1 epidemic., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Three novel furoquinoline alkaloid oxogeranyl ethers (1-3) and one known furoquinoline alkaloid (4) were isolated from the leaves of Boninia glabra, an endemic plant of the Bonin Islands. Their structures were elucidated on the basis of spectroscopic analysis.