The prevalence and factors associated with nonalcoholic fatty liver disease (NAFLD) are largely unknown in HIV-1 monoinfected patients.
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.
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<0.001), dyslipidemia (adjusted OR = 2.045; 95% CI, 1.183-3.538; p = 0.010), and higher ALT to AST ratio (per 1 increment, adjusted OR = 3.557; 95% CI, 2.129-5.941; p<0.001) as significant factors associated with NAFLD. No HIV-specific variables, including treatment with dideoxynucleoside analogues (didanosine, stavudine, and zalcitabine) and cumulative duration of antiretroviral therapy (ART), were associated with NAFLD.
The incidence of NALFD among Asian patients with HIV-1 infection is similar to that in Western countries. NAFLD was associated with high BMI, dyslipidemia, and high ALT/AST ratio, but not with HIV-related factors. The results highlight the importance of early recognition and management of NAFLD and traditional factors associated with NAFLD for Asian patients with HIV-1 infection.
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.
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.
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.
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<0.001)(per 1 kg/m(2) decrement, HR = 1.14; 95% CI, 1.05-1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01-1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00-1.16; p = 0.058).
The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir.
In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular ...filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested.
A single-center observational study.
The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR < 60) were estimated with logistic regression model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model.
A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR.
Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.
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 (<33 years versus >40, HR 4.0, 95%CI 2.22-7.18, p<0.001), history of syphilis at baseline (HR 3.0, 95%CI 2.03-4.47, p<0.001), positive anti-amoeba antibody (HR 1.8, 95%CI 1.17-2.68, p = 0.006), and high baseline CD4 count (CD4 ≥350 /μL versus CD4 <200, HR 1.6, 95%CI 1.00-2.53, p = 0.050) as risk factors for incident syphilis. Incidence of syphilis was particularly high among young patients (age <33 years: 60.1/1,000 person-years). Interestingly, 37% of patients with incident syphilis were asymptomatic.
Although incidence of syphilis did not increase during the observation period, it was high among HIV-1-infected MSM, especially among young HIV-1-infected MSM and those with history of syphilis, in Tokyo. Regular screening for syphilis needs to be strictly applied to this population.
► Relatively little is known regarding how reduction of physical activity affects brain function. ► Cessation of running performed during the growth period is anxiogenic. ► Cessation of running ...inhibited the differentiation of new cells to immature neurons. ► Reduction of physical activity is likely a risk factor for impaired hippocampal function.
While increasing evidence demonstrates that physical exercise promotes brain health, little is known on how the reduction of physical activity affects brain function. We investigated whether the cessation of wheel running alters anxiety-like and depression-like behaviors and its impact on adult hippocampal neurogenesis in mice. Male C57BL/6 mice (4 weeks old) were assigned to one of the following groups, and housed until 21 weeks old; (1) no exercise control (noEx), housed in a standard cage; (2) exercise (Ex), housed in a running wheel cage; and (3) exercise–no exercise (Ex–noEx), housed in a running wheel cage for 8 weeks and subsequently in a standard cage. Behavioral evaluations suggested that Ex–noEx mice were more anxious compared to noEx control mice, but no differences were found in depression-like behavior. The number of BrdU-labeled surviving cells in the dentate gyrus was significantly higher in Ex but not in Ex–noEx compared with noEx, indicating that the facilitative effects of exercise on cell survival are reversible. Surprisingly, the ratio of differentiation of BrdU-positive cells to doublecortin-positive immature neurons was significantly lower in Ex–noEx compared to the other groups, suggesting that the cessation of wheel running impairs an important component of hippocampal neurogenesis in mice. These results indicate that hippocampal adaptation to physical inactivity is not simply a return to the conditions present in sedentary mice. As the impaired neurogenesis is predicted to increase a vulnerability to stress-induced mood disorders, the reduction of physical activity may contribute to a greater risk of these disorders.
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.
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.
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%).
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.
The Spectrum-STI model, structured by sub-groups within a population, was used in a workshop in Yunnan, China, to estimate provincial trends in active syphilis in 15 to 49-year-old adults. Syphilis ...prevalence data from female sex workers (FSW), men who have sex with men (MSM), and lower-risk women and men in Yunnan were identified through literature searches and local experts. Sources included antenatal care clinic screening, blood donor screening, HIV/STI bio-behavioural surveys, sentinel surveillance, and epidemiology studies. The 2017 provincial syphilis prevalence estimates were 0.26% (95% confidence interval 0.17-0.34%) in women and 0.28% (0.20-0.36%) in men. Estimated prevalence was 6.8-fold higher in FSW (1.69% (0.68-3.97%) than in lower-risk women (0.25% (0.18-0.35%)), and 22.7-fold higher in MSM (5.35% (2.74-12.47%) than in lower-risk men (0.24% (0.17-0.31%). For all populations, the 2017 estimates were below the 2005 estimates, but differences were not significant. In 2017 FSW and MSM together accounted for 9.3% of prevalent cases. These estimates suggest Yunnan's STI programs have kept the overall prevalence of syphilis low, but prevalence remains high in FSW and MSM. Strengthening efforts targeting FSW and MSM, and identification of other risk populations e.g. among heterosexual men, are critical to reduce syphilis.
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<0.01) and decrease in HIV-infected patients (13.6% to 9.0%; P=0.097). Multivariate analysis revealed increasing age (odds ratio OR, 1.02; p=0.007), HIV infection (OR, 4.92; p<0.001), and corticosteroid use (OR, 5.90; p<0.001) were significantly associated with CE, and smoking (OR, 1.32; p=0.085) and acetaminophen use (OR, 1.70; p=0.097) were marginally associated. No significant association was found with alcohol consumption, hepatitis B or C virus, syphilis, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease, liver cirrhosis, anticancer, or PPIs use. In HIV-infected patients, CD4 cell count <100/μL (OR, 4.83; p<0.001) and prior HAART (OR, 0.35; p=0.006) were independently associated with CE, but sexual behavior was not. Among corticosteroid users, CE was significantly associated with higher prednisone-equivalent dose (p=0.043 for trend test).
This large, endoscopy-based study demonstrated that CE prevalence increased in non-HIV-infected patients but decreased in HIV-infected patients over 13 years. Risk analysis revealed that increasing age, HIV infection, and corticosteroids use, particularly at higher doses, were independently associated with CE, but alcohol, other infections, diabetes, anticancer drugs, and PPIs use were not.
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.
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