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IntroductionEnvironmental enrichment (EE) improves various health outcomes, such as hippocampal neurogenesis, in rodents, which is thought to be caused, in part, by increased physical activity. However, the specific effect of each enrichment component, such as enlarged housing spaces and increased spatial complexity with a variety of objects, on physical activity remains unclear because of methodological limitations in measuring physical activity. We aimed to examine whether enlarged housing spaces and increased spatial complexity increase physical activity in mice using a body-implantable actimeter.MethodsAdult male C57BL/6J mice were assigned to either standard housing or EE groups. The housing environment in the EE mice was gradually enriched by enlarging the housing space and the placement of a variety of objects. Physical activity was measured using a body-implanted actimeter. Hippocampal neurogenesis was immunohistochemically examined.ResultsEnlarged housing spaces and the placement of a variety of objects did not increase physical activity in mice. In contrast, hippocampal neurogenesis was enhanced in the EE mice, suggesting that environmental interventions successfully provided enriched housing conditions for these mice.ConclusionsThese results indicate that enlarged housing spaces and increased spatial complexity do not increase physical activity in mice. Furthermore, we found that EE enhanced hippocampal neurogenesis without increasing activity volume. Besides the current understanding that increasing the amount of physical activity is key to improving hippocampal function, our result suggests that the environment in which physical activity takes place is also a crucial contextual factor in determining the impact of physical activity on hippocampal function.

Abstract Background Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. Methods We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. Results A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8–24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6–23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6–17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1–56.4%). Conclusions PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG.

ABSTRACT: Objective: To investigate changes in weight following the initiation of antiretroviral therapy in treatment-naïve Asian people living with human immunodeficiency virus (PLWH). Methods: This retrospective observational study evaluated adult treatment-naïve Asian PLWH who started antiretroviral therapy based on an integrase strand transfer inhibitor, a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor at the AIDS Clinical Centre, Tokyo between January 2005 and February 2019. Patients were followed-up until October 2019. Multi-variate linear mixed-effects models were used to generate marginal predictions of weight over time. Predicted weight was reported at 3-month intervals until censoring or for 5 years after treatment initiation. Results: Five years after treatment initiation, average weight gain in PLWH who started on dolutegravir-, darunavir- and elvitegravir-based treatment was 5.3 kg, 4.1 kg and 4.6 kg, respectively, while those who started on raltegravir-, lopinavir- and atazanavir-based treatment gained an average of 1.9 kg, 2.1 kg and 2.3 kg, respectively. Average weight gain in PLWH who started treatment with the backbone drugs, tenofovir alafenamide, abacavir and tenofovir disproxil fumarateb was 4.1 kg, 3.0 kg and 3.0 kg, respectively, and those treated with dolutegravir plus tenofovir alafenamide/emtricitabine gained an average of 6.7 kg. Conclusions: Antiretroviral-therapy-associated weight gain continued to increase for 5 years following treatment initiation. A combination of dolutegravir and tenofovir alafenamide/emtricitabine was associated with the greatest weight gain.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010–2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

Objectives: To estimate prevalence levels of and time trends for active syphilis, gonorrhoea and chlamydia in women aged 15–49 years in four countries in the Pacific (Fiji, the Federated States of Micronesia [FSM], Papua New Guinea [PNG] and Samoa) to inform surveillance and control strategies for sexually transmitted infections (STIs). Methods: The Spectrum-STI model was fitted to data from prevalence surveys and screenings of adult female populations collected during 1995−2017 and adjusted for diagnostic test performance and to account for undersampled high-risk populations. For chlamydia and gonorrhoea, data were further adjusted for age and differences between urban and rural areas. Results: Prevalence levels were estimated as a percentage (95% confidence interval). In 2017, active syphilis prevalence was estimated in Fiji at 3.89% (2.82 to 5.06), in FSM at 1.48% (0.93 to 2.16), in PNG at 3.91% (1.67 to 7.24) and in Samoa at 0.16% (0.07 to 0.37). For gonorrhoea, the prevalence in Fiji was 1.63% (0.50 to 3.87); in FSM it was 1.59% (0.49 to 3.58); in PNG it was 11.0% (7.25 to 16.1); and in Samoa it was 1.61% (1.17 to 2.19). The prevalence of chlamydia in Fiji was 24.1% (16.5 to 32.7); in FSM it was 23.9% (18.5 to 30.6); in PNG it was 14.8% (7.39 to 24.7); and in Samoa it was 30.6% (26.8 to 35.0). For each specific disease within each country, the 95% confidence intervals overlapped for 2000 and 2017, although in PNG the 2017 estimates for all three STIs were below the 2000 estimates. These patterns were robust in the sensitivity analyses. Discussion: This study demonstrated a persistently high prevalence of three major bacterial STIs across four countries in WHO’s Western Pacific Region during nearly two decades. Further strengthening of strategies to control and prevent STIs is warranted.

Abstract Background Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. Methods Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox’s proportional hazards model was used to estimate hazard ratios (HR). Results During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40–59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40–49, 50–59, 60–69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8–0.9, P

Objective: To investigate the association between anorectal precancerous lesions, including condyloma, and sexually transmitted infections (STI) in Asian population. Methods: This prospective study enrolled 2677 patients who underwent high-resolution colonoscopy for anorectal cancer screening. Anorectal lesions were diagnosed based on endoscopic findings and confirmed by biopsy. The association of HIV-1 infection, syphilis, and HBV infection with anorectal lesion was estimated by multivariate logistic regression. In HIV-1-infected patients (n=244), anal canal HPV-DNA was screened and genotyped. Results: Although no malignancy was identified, anorectal condyloma was diagnosed in 32 (1.2%) male patients. 41% of anorectal condyloma cases had no specific lower GI symptoms. Multivariate analysis identified HIV-1 infection, but not syphilis or HBV infection, as an independent significant factor for condyloma (OR: 176.5, 95%CI 22.52-1383, p

Populations worldwide are increasingly becoming physically inactive, which is related to somatic and psychological health problems that are prevalent in modern society. Recent epidemiological studies have indicated that the associations between physical inactivity and depression are bidirectional. Numerous animal studies have demonstrated that exercise improves hippocampal function. Because the hippocampus is a pivotal brain region that exerts inhibitory control over stress responses by affecting the hypothalamus-pituitary-adrenal axis, enhanced hippocampal function by exercise can increase stress resilience, which helps prevent stress-related depression. In contrast, physical inactivity is difficult to model in animal studies, and little is known about the effects of physical inactivity on the rodent hippocampus. To fill this gap, we previously developed a mouse model of habituated voluntary wheel running cessation as a reverse intervention to control physical activity. We found that reducing physical activity by cessation of wheel running impairs hippocampal neurogenesis in mice. Thus, this review discusses the relevant literature and provides a hypothesis that physical inactivity can be a potential risk factor for stress-related depression as it increases stress vulnerability by impairing hippocampal function.

Increasing clinical evidence suggests that regular physical exercise can prevent or reduce the incidence of stress-related psychiatric disorders including depressive symptoms. Antidepressant effect of regular exercise may be implicated in monoaminergic transmission including serotonergic transmission, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis, but few general concepts regarding the optimal exercise regimen for stimulating neural mechanisms involved in antidepressant properties have been developed. Here, we examined how 4 weeks of treadmill running at different intensities (0, 15, 25 m/min, 60 min/day, 5 times/week) alters neuronal activity in the dorsal raphe nucleus (DRN), which is the major source of serotonin (5-HT) neurons in the central nervous system, and the hypothalamic paraventricular nucleus (PVN), in which corticotropin-releasing factor (CRF) neurons initiate the activation of the HPA axis, during one session of acute treadmill running at different speeds (0, 15, 25 m/min, 30 min) in male Wistar rats, using c-Fos immunohistochemistry. We also examined neurogenesis in the hippocampus using immunohistochemistry for doublecortin (DCX) and assessed depressive-like behavior using the forced swim test after regular exercise for 4 weeks. In the pre-training period, acute treadmill running at low speed, but not at high speed, increased c-Fos positive nuclei in the DRN compared with the sedentary control. The number of c-Fos positive nuclei in the PVN during acute treadmill running was increased in a running speed-dependent manner. Regular exercise for 4 weeks, regardless of the training intensity, induced an enhancement of c-Fos expression in the DRN during not only low-speed but also high-speed acute running, and generally reduced c-Fos expression in the PVN during acute running compared with pre-training. Furthermore, regular treadmill running for 4 weeks enhanced DCX immunoreactivity in the hippocampal dentate gyrus (DG), and resulted in decreased depressive-like behavior, regardless of the training intensity. These results suggest that long-term repeated exercise, regardless of the training intensity, improves depressive-like behavior through adaptive changes in the sensitivity of DRN and PVN neurons to acute exercise, and hippocampal neurogenesis.

Previous studies have demonstrated that an acute bout of aerobic exercise induces a subsequent delayed onset of hypoglycemia among patients with type 1 diabetes. However, the mechanisms of exercise-induced hypoglycemia in type 1 diabetes are still unclear. Streptozotocin (STZ) was injected to 6-week-old male Wistar rats, and three days after STZ injection, animals were randomly assigned into 2 groups: STZ with insulin only (STZ) and STZ with insulin and exercise (STZ+EX). Normal Wistar rats with exercise were used as control (CON+EX). Insulin was intraperitoneally injected (0.5 U/kg) to both STZ groups (-0.5 h), and a bout of aerobic exercise (15 m/min for 30 min) was conducted at euglycemic conditions (0 h). Blood was collected at 0, 1, 3, and 5 h after exercise from the carotid artery. While the blood glucose level was stable during the post-exercise period (0-5 h) in the STZ and CON+EX groups, it decreased significantly only in the STZ+EX group at 3 h. Plasma glucagon, adrenalin, and noradrenalin levels significantly increased at 1 h in the STZ group, whereas significant hormonal responses were observed at 5 h in the STZ+EX group. In skeletal muscle glucose metabolism-related pathway, the level of glucose transporter-4 (GLUT-4) translocation was significantly higher at 1 h in the CON and STZ groups. However, in the STZ+EX group, these activations were maintained by 5 h, indicating a sustained glucose metabolism in the STZ+EX group. A single bout of aerobic exercise induced a delayed onset of hypoglycemia in STZ-treated rats. A prolonged enhancement of GLUT-4 translocation and delayed counter-regulatory hormone responses may have contributed to the induction of hypoglycemia.

The epidemiology of incident syphilis infection among HIV-1-infected men who have sex with men (MSM) largely remains unknown.The incidence and risk factors for incident syphilis (positive TPHA and RPR> = 1:8) among HIV-1-infected MSM who visited a large HIV clinic in Tokyo for the first time between 2008 and 2013 were determined, using clinical data and stored blood samples taken every three months for screening and determination of the date of incident syphilis. Poisson regression compared the incidence of syphilis at different observation periods.Of 885 HIV-1-infected MSM with baseline data, 34% either presented with active syphilis at baseline (21%) or became infected with syphilis during follow-up (13%). After excluding 214 patients (MSM with syphilis at baseline (n = 190) and no follow-up syphilis test (n = 24)), of 671 men, 112 (17%) developed incident syphilis with an incidence of 43.7/1,000 person-years [95% CI, 36.5-52.3]. The incidence decreased slightly during observation period although the trend was not significant (2008-2009: 48.2/1,000 person-years, 2010-2011: 51.1/1,000 person-years, 2012-2013: 42.6/1,000 person-years, 2014 to 2015: 37.9/1,000 person-years, p = 0.315). Multivariable analysis identified young age (40, HR 4.0, 95%CI 2.22-7.18, p

Little information is available on the mortality and risk factors associated with death in disseminated non-tuberculous mycobacterial infection (dNTM) in HIV-infected patients in the ART-era.In a single-center study, HIV-infected dNTM with positive NTM culture from sterile sites between 2000 and 2013 were analysed. The clinical characteristics at commencement of anti-mycobacterial treatment (baseline) were compared between those who survived and died.Twenty-four patients were analyzed. [The median CD4 27/μL (range 2-185)]. Mycobacterium avium and M. intracellulare accounted for 20 (83%) and 3 (13%) of isolated NTM. NTM bacteremia was diagnosed in 15 (63%) patients. Seven (29%) patients died, and NTM bacteremia was significantly associated with mortality (p = 0.022). The baseline CD4 count was significantly lower in the non-survivors than the survivors (median 7/μL versus 49, p = 0.034). Concomitant AIDS-defining diseases or malignancies were not associated with mortality. Immune-reconstitution syndrome (IRS) occurred to 19 (79%) patients (8 paradoxical and 11 unmasking), and prognosis tended to be better in unmasking-IRS than the other patients (n = 13) (p = 0.078). Patients with paradoxical-IRS had marginally lower CD4 count and higher frequency of bacteremia than those with unmasking-IRS (p = 0.051, and 0.059). Treatment with systemic corticosteroids was applied in 63% and 55% of patients with paradoxical and unmasking-IRS, respectively.dNTM in HIV-infected patients resulted in high mortality even in the ART-era. NTM bacteremia and low CD4 count were risk factors for death, whereas patients presented with unmasking-IRS had marginally better prognosis. IRS occurred in 79% of the patients, suggesting difficulty in the management of dNTM.

BackgroundThe current guidelines recommend 21-day adjunctive corticosteroid therapy for HIV-1-infected pneumocystis pneumonia patients (HIV-PCP) with moderate-to-severe disease. Whether shorter adjunctive corticosteroid therapy is feasible in such patients is unknown.MethodsWe conducted a retrospective study to elucidate the proportion of patients with moderate and severe HIV-PCP who required adjunctive corticosteroid therapy for 21 days. The enrollment criteria included HIV-PCP that fulfilled the current criteria for 21-day corticosteroid therapy; PaO2 on room air of ResultsThe median duration of corticosteroid therapy in the 73 study patients was 13 days (IQR 9-21). Adjunctive corticosteroid therapy was effective and discontinued within 10 and 14 days in 30% and 60% of the patients, respectively. Only 9% of the patients with moderate HIV-PCP (n = 22, A-aDO2 35-45 mmHg) received steroids for >14 days, whereas 35% of the patients with severe HIV-PCP (n = 51, A-aDO2 ≥45 mmHg) required corticosteroid therapy for ≥21 days. Four (13%) of the severe cases died, whereas no patient with moderate disease died. Among patients with severe HIV-PCP, discontinuation of corticosteroid therapy within 14 days correlated significantly with higher baseline CD4 (p = 0.049).ConclusionShorter adjunctive corticosteroid therapy was clinically effective and adjunctive corticosteroid could be discontinued within 14 days in 60% of moderate-to-severe HIV-PCP and 90% of moderate cases.

ObjectiveTo investigate whether routine eye screening by an ophthalmologist in patients with HIV-1 infection is clinically useful.MethodsA single-center, retrospective study in Tokyo, Japan. HIV-1-infected patients aged over 17 years who visited our clinic for the first time between January 2004 and December 2013 and underwent full ophthalmologic examination were enrolled. At our clinic, ophthalmologic examination, including dilated retinal examination by indirect ophthalmoscopy was routinely conducted by ophthalmologists on the first visit. The prevalence of ophthalmologic diseases and associated factors including the existence of ocular symptoms were analyzed.ResultsOf the 1,515 study patients, cytomegalovirus retinitis (CMV-R) was diagnosed in 24 (2%) patients, HIV retinopathy (HIV-R) in 127 (8%), cataract in 31 (2%), ocular syphilis in 4 (0.3%), and uveitis with unknown cause in 8 (0.5%). Other ocular diseases were diagnosed in 14 patients. The CD4 count was ConclusionsRoutine ophthalmologic screening is recommended for HIV-1-infected patients with CD4

Japan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%).A single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed.The 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/μL) was significantly higher than that of patients who had never been tested (203/μL, p

The prevalence of candida esophagitis (CE) might be changing in an era of highly active antiretroviral therapy (HAART) among HIV-infected patients or today's rapidly aging society among non-HIV-infected patients. However, few studies have investigated long-term CE trends, and CE risk factors have not been studied in a large sample, case-control study. This study aimed to determine long-term trends in CE prevalence and associated risk factors for patients with or without HIV infection.Trends in CE prevalence were explored in a cohort of 80,219 patients who underwent endoscopy between 2002 and 2014. Risks for CE were examined among a subcohort of 6,011 patients. In risk analysis, we assessed lifestyles, infections, co-morbidities, immunosuppressants, and proton-pump inhibitors (PPIs). All patients were tested for HIV, hepatitis B or C virus, and syphilis infection. For HIV-infected patients, sexual behavior, CD4 cell count, history of HAART were also assessed.CE prevalence was 1.7% (1,375/80,219) in all patients, 9.8% (156/1,595) in HIV-infected patients, and 1.6% (1,219/78,624) in non-HIV-infected patients. CE prevalence from 2002-2003 to 2012-2014 tended to increase in non-HIV-infected patients (0.6% to 2.5%; P

To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement.This study investigated the association between 3 SNPs (ABCC2-24, 1249, and ABCB1 2677), which are shown to be associated with TDF-induced tubulopathy, and clinically important renal outcomes (>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR, and eGFR 10ml/min/1.73m2 and those without such decrement (ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p = 0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR

Oncogenic human papillomavirus (HPV) infection, particularly multiple HPV types, is recognized as a necessary cause of anal cancer. However, a limited number of studies have reported the prevalence of anal HPV infection in Asia. We determined the prevalence, genotypes, and risk factors for anal HPV infection in Japanese HIV-positive men who have sex with men (MSM), heterosexual men, and women.This cross-sectional study included 421 HIV-positive patients. At enrollment, we collected data on smoking, alcohol, co-morbidities, drugs, CD4 cell counts, HIV RNA levels, highly active anti-retroviral therapy (HAART) duration, sexually transmitted infections (STIs), and serological screening (syphilis, hepatitis B virus, Chlamydia trachomatis, Entamoeba histolytica). Anal swabs were collected for oncogenic HPV genotyping.Oncogenic HPV rate was 75.9% in MSM, 20.6% in heterosexual men, and 19.2% in women. HPV 16/18 types were detected in 34.9% of MSM, 17.7% of heterosexual men, and 11.5% of women. Multiple oncogenic HPV (≥2 oncogenic types) rate was 54.6% in MSM, 8.8% in heterosexual men, and 0% in women. In univariate analysis, younger age, male sex, MSM, CD4 50,000, no administration of HAART, and having ≥2 sexually transmitted infections (STIs) were significantly associated with oncogenic HPV infection, whereas higher smoking index and corticosteroid use were marginally associated with oncogenic HPV infection. In multivariate analysis, younger age (OR, 0.98 [0.96-0.99]), MSM (OR, 5.85 [2.33-14.71]), CD4

BACKGROUND: The prevalence and factors associated with nonalcoholic fatty liver disease (NAFLD) are largely unknown in HIV-1 monoinfected patients. METHODS: The present study elucidated the prevalence and factors associated with NAFLD among Asian patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Diagnosis of NAFLD was based on the liver to kidney contrast and diffusion in hepatic echogenicity. Uni- and multi-variate logistic regression analyses were applied to estimate factors associated with NAFLD. RESULTS: 435 Asian patients free of chronic hepatitis B or C virus infection and without excessive alcohol intake were analyzed. NAFLD was diagnosed in 135 (31%) patients. Obesity (BMI >30 kg/m(2)) was evident in 18 (4.1%) patients, and BMI was >25 kg/m(2) in 103 (24%). Multivariate analysis identified higher BMI (per 1 kg/m(2) increment, adjusted OR = 1.198; 95% CI, 1.112-1.290; p

OBJECTIVE: The 2010 WHO antiretroviral therapy (ART) guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD) in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country. DESIGN: Cross-sectional study was performed. METHODS: Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD. RESULTS: Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291), body weight per 1 kg-decrement (1.286, 1.193-1.386), and tenofovir use (2.715, 1.028-7.168) as risk factors for CKD. CONCLUSIONS: Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients.

Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral load.This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks calculated with Cockcroft-Gault equation.58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3 (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026). Per protocol analysis showed that the HIV-RNA was 10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load.ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J).

OBJECTIVE: To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%. DESIGN: A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan. METHODS: The prevalence of illicit drug use and the association of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use. RESULTS: 1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88-7.36; p40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤ 30 years: adjusted OR = 7.56; 95% CI, 2.86-20.0; p40 years: adjusted OR = 6.15; 95% CI, 2.40-15.8; p

BACKGROUND: Loss to follow up (LTFU) is an important prognostic factor in patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients with HIV-1 infection is unknown in Japan. METHODS: A single center observational study was conducted to elucidate the impact of illicit drug use on LTFU at a large HIV clinic in Tokyo. LTFU was defined as those who discontinued their visits to the clinic for at least 12 months and were not known to be under the care of other facilities or have died within 12 months of their last visit. Patients who first visited the clinic between January 2005 and August 2010 were enrolled. Information on illicit drug use was collected in a structured interview and medical charts. Comparison of the effects of illicit drug use and no use on LTFU was conducted by uni- and multi-variate Cox hazards models as the primary exposure. RESULTS: The study subjects were 1,208 patients, mostly Japanese men, of relatively young age, and infected through homosexual contact. A total of 111 patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni- and multi-variate analyses showed that illicit drug use was a significant risk for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI, 1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4 count, no antiretroviral therapy, and no health insurance as risk factors for LTFU. CONCLUSIONS: The incidence of LTFU among illicit drug users was almost twice higher than that among non users. Effective intervention for illicit drug use in this population is warranted to ensure proper treatment and prevent the spread of HIV.

OBJECTIVE: To compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs). DESIGN: We conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy. METHODS: The incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure. RESULTS: Complicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275-6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276-7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively. CONCLUSION: In this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r.

Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso-ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise-induced hippocampal plasticity.

BACKGROUND:Although ritonavir-boosted atazanavir (ATV/r) is known to be associated with nephrolithiasis, little is known about the incidence of nephrolithiasis in patients treated with ritonavir-boosted Darunavir (DRV/r), the other preferred protease inhibitor. METHODS:In a single-center cohort, the incidence of nephrolithiasis was compared between HIV-infected patients who commenced DRV/r-containing antiretroviral therapy and those on ATV/r. The effects of ATV/r use over DRV/r were estimated by univariate and multivariate Cox hazards models. RESULTS:Renal stones were diagnosed in only one patient (0.86 per 1000 person-years) of the DRV/r group (n=540) and 37 (20.2 per 1000 person-years) of the ATV/r group (n=517). The median [interquartile (IQR)] observation period in the DRV/r group was 27.1 months (IQR 18.1-38.4 months), and 40.6 months (IQR 17.5-42.7) for the ATV/r group. The total observation period was 1,163.6 person-years and 1,829.6 person-years for the DRV/r group and for the ATV/r group, respectively. In the 37 patients on ATV/r who developed nephrolithiasis, the median time from commencement of ATV/r to diagnosis was 28.1 months (IQR 18.4-42.7), whereas nephrolithiasis in the single patient of the DRV/r group occurred 11.2 month after the introduction of DRV/r. ATV/r use over DRV/r was significantly associated with nephrolithiasis by uni- and multivariate analyses (HR=26.01; 95% CI, 3.541-191.0; p=0.001) (adjusted HR=21.47; 95% CI, 2.879-160.2; p=0.003). CONCLUSION:The incidence of nephrolithiasis was substantially lower in patients on DRV/r than those on ATV/r. The results suggest that DRV/r should be selected for treatment of HIV-infected patients at risk of chronic kidney disease.

BACKGROUND: The efficacy of preemptive therapy against cytomegalovirus (CMV) infection remains unknown in treatment-naïve patients with advanced HIV-1 infection in the HAART era. METHODS: The subjects of this single-center observation study were 126 treatment-naïve HIV-1 infected patients with positive CMV viremia between January 1, 2000 and December 31, 2006. Inclusion criteria were age more than 17 years, CD4 count less than 100/μl, plasma CMV DNA positive, never having received antiretroviral therapy (ART) and no CMV end-organ disease (EOD) at first visit. The incidence of CMV-EOD was compared in patients with and without preemptive therapy against CMV-EOD. The effects of the CMV preemptive therapy were estimated in uni- and multivariate Cox hazards models. RESULTS: CMV-EOD was diagnosed in 30 of the 96 patients of the non-preemptive therapy group (31%, 230.3 per 1000 person-years), compared with 3 of the 30 patients of the preemptive therapy group (10%, 60.9 per 1000 person-years). Univariate (HR = 0.286; 95%CI, 0.087-0.939; p = 0.039) and multivariate (adjusted HR = 0.170; 95%CI, 0.049-0.602; p = 0.005) analyses confirmed that CMV-EOD is significantly prevented by CMV preemptive therapy. Multivariate analysis showed that plasma CMV DNA level correlated significantly with CMV-EOD (per log10/ml, adjusted HR = 1.941; 95%CI, 1.266-2.975; p = 0.002). Among the 30 patients on preemptive therapy, 7 (23.3%) developed grade 3-4 leukopenia. The mortality rate was not significantly different between the two groups (p = 0.193, Log-rank test). CONCLUSIONS: The results indicate that preemptive therapy lowers the incidence of CMV-EOD by almost 25%. Preemptive therapy for treatment-naïve patients with CMV viremia is effective, although monitoring of potential treatment-related side effects is required.

OBJECTIVE: To compare the rate of decline of renal function in tenofovir- and abacavir-based antiretroviral therapy (ART) in low-body weight treatment-naïve patients with HIV infection. DESIGN: We conducted a single-center retrospective cohort study of 503 Japanese patients who commenced on either tenofovir- or abacavir-based initial ART. METHODS: The incidence of renal dysfunction, defined as more than 25% fall in estimated glomerular filtration rate (eGFR) from the baseline, was determined in each group. The effect of tenofovir on renal dysfunction was estimated by univariate and multivariate Cox hazards models as the primary exposure. Changes in eGFR until 96 weeks were estimated in both groups with a repeated measures mixed model. RESULTS: The median body weight of the cohort was 64 kg. The estimated incidence of renal dysfunction in the tenofovir and the abacavir arm was 9.84 per 100 and 4.55 per 100 person-years, respectively. Tenofovir was significantly associated with renal dysfunction by univariate and multivariate analysis (HR = 1.747; 95% CI, 1.152-2.648; p = 0.009) (adjusted HR = 2.080; 95% CI, 1.339-3.232; p68 kg: adjusted HR = 0.997; 95%CI, 0.318-3.121; p = 0.995). The fall in eGFR was significantly greater in the tenofovir arm than the abacavir arm after starting ART (p = 0.003). CONCLUSION: The incidence of renal dysfunction in low body weight patients treated with tenofovir was twice as high as those treated with abacavir. Close monitoring of renal function is recommended for patients with small body weight especially those with baseline body weight

BACKGROUND: Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. METHODS: In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. RESULTS: The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10-1.37; p

This article provides an overview of the challenges faced by the World Health Organization (WHO) and its Member States in the Western Pacific Region in managing COVID-19 clinical cases and healthcare pathways. It discusses issues such as overwhelmed hospitals, inadequate resources, and staff shortages. The article emphasizes the importance of sharing experiences and scientific evidence to improve care pathways and preparedness for future pandemics. The authors express their gratitude for the support and guidance they received from the WHO and state that they have no conflicts of interest. [Extracted from the article]