Community-based screening enhances hepatitis B virus linkage to care among West African migrants in Spain.

BACKGROUND: Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. METHODS: This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. RESULTS: In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days. CONCLUSIONS: This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.

A large proportion of hepatitis B virus (HBV) infections occur within countries in sub-Saharan Africa. With recent increased migration from these countries to Catalonia Spain, the prevalence of HBV is greater in migrants than in host populations. However, migrants face additional barriers when trying to access care. We developed a community-based care pathway to provide migrants in Catalonia with access to HBV testing, post-test counseling, vaccinations, and appointments with specialists when needed. The results showed that this strategy was successful in increasing testing, linkage to care, and vaccination among at-risk migrant populations in Catalonia, Spain. It may be worthwhile implementing this strategy on a wider scale and with other at-risk populations to reduce HBV infections and improve outcomes.

Chronic conditions and multimorbidity among West African migrants in greater Barcelona, Spain.

Objectives: This study aimed to report the prevalence and identify potential risk factors of chronic conditions among West African migrants living in the greater Barcelona area, Spain, and explore the relationship between years of residence in Spain and chronic disease burden. Methods: This cross-sectional study included 436 adult African migrants who participated in a community-based hepatitis B virus (HBV) screening and vaccination program (HBV-COMSAVA) in the greater Barcelona area from 21 November 2020 to 22 January 2022. Data were analyzed using standard descriptive statistics and bivariable and multivariable logistic regression. Results: HBV, non-communicable diseases (NCDs) and metabolic risk factors, and multimorbidity prevalence were 9.17, 20.87, and 4.13%, respectively. Being male or having been previously tested for HBV were associated with higher odds of HBV positivity. Associated risk factors for NCDs and metabolic risk factors included living in Spain for >5 years, being female, and being aged ≥50 years. Conclusion: The high prevalence of chronic conditions in migrant populations supports a need for early detection strategies and tailored public health interventions that aim to reduce the disease burden imposed on migrants and on health systems in host countries.

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate for Nonoccupational HIV-1 Postexposure Prophylaxis: A Prospective Open-Label Trial (DORAVIPEP).

Background: New regimens may provide better tolerability, convenience, and safety for nonoccupational human immunodeficiency virus (HIV) postexposure prophylaxis (PEP). For this reason, we evaluated the single-tablet regimen of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for 28 days. Methods: This was a prospective, open-label, single-arm trial including individuals with potential HIV-1 exposure within 72 hours. The primary endpoint was noncompletion of PEP at day 28. Secondary endpoints were adverse effects, adherence, and rate of seroconversion. We performed follow-up at day 7, week 4, and week 12. Results: Between September 2019 and March 2022, the study enrolled 399 individuals. Median age was 30 (interquartile range [IQR], 27-36) years, and 91% (n = 364) were male. The mode of exposure was sex between men in 84% (n = 331) of cases; risk assessment for HIV-1 transmission was considered as "high" in 97% (n = 385) of the participants. Median time from exposure to consultation was 24 (IQR, 13-40) hours. Noncompletion of PEP was 29% (n = 114) (95% confidence interval [CI], 24%-33%) and 20% (n = 72) (95% CI, 16%-25%) per modified intention-to-treat. Main reasons for noncompletion were loss to follow-up (n = 104 [91%]) and intolerance (n = 8 [7%]). Older age was associated with a lower risk of premature discontinuation (OR, 0.94; P < .001). One hundred twenty-three (31%) participants reported adverse events, mostly mild and self-limited (82%); discontinuation occurred in 8 cases (2%). Adherence to PEP in the assessed users was 96%. There were no HIV seroconversions. Conclusions: DOR/3TC/TDF is a well-tolerated option for nonoccupational PEP. Clinical Trials Registration. NCT04233372.

Beyond the effects of HIV infection and integrase inhibitors-based therapies on oral bacteriome.

Oral microbiome is the second largest microbial community in humans after gut. Human immunodeficiency virus (HIV) infection triggers an impairment of the immune system which could favour the growth and the colonization of pathogens in the oral cavity, and this dysbiosis has been associated with oral manifestations that worsen the quality of life of these patients. Antiretroviral therapy (ART) could also drive changes in specific oral bacterial taxa associated with such periodontal diseases. Integrase strand transfer inhibitors (INSTIs), therapy of choice in the treatment of naive HIV-patients, are able to reverse the impact of HIV infection on systemic inflammation, gut permeability, and gut bacterial diversity/richness. The objective of this study was to analyse the effects of HIV infection per se and INSTIs on salivary bacteriome composition, taking into consideration other factors such as smoking, that could also have a significant impact on oral microbiome. To accomplish this objective, 26 non-HIV-infected volunteers and 30 HIV-infected patients (15 naive and 15 under INSTIs-regimen) were recruited. Salivary samples were collected to measure lysozyme levels. Oral bacteriome composition was analysed using 16S rRNA gene sequencing. Naive HIV-infected patients showed statistically higher levels of lysozyme compared to controls (p < 0.001) and INSTIs-treated patients (p < 0.05). Our study was unable to detect differences in α nor ß-diversity among the three groups analysed, although significant differences in the abundance of some bacterial taxonomical orders were detected (higher abundance in the phylum Pseudomonadota, in the order Acholeplasmatales, and in the genera Ezakiella and Acholeplasma in the naive group compared to controls; and higher abundance in the phylum Mycoplasmatota, in the order Acholeplasmatales, and in the genera Acholeplasma and uncultured Eubacteriaceae bacterium in the INTIs-treated HIV-infected patients compared to controls). These differences seem to be partially independent of smoking habit. HIV infection and INSTIs effects on oral microbiota seem not to be very potent, probably due to the modulation of other factors such as smoking and the greatest outward exposure of the oral cavity.

Perception of quality of care using patient reported experience measures (PREMs) in a cohort of adults with HIV: A cross-sectional study.

Human immunodeficiency virus (HIV) infection is considered a chronic disease. Antiretroviral therapy has allowed persons with HIV (PLWHIV) to achieve the 90-90-90 objectives proposed by the World Health Organization for 2020; but an additional challenge is getting an adequate health-related quality of life. A determining factor in the health-related quality of life of PLWHIV is the health care they perceive to receive. In this sense, we aimed to assess the perception of the outpatient care provided and to identify possible areas for improvement in a single-center, cross-sectional study at the HIV unit of Hospital Clínic, Barcelona. We sought patient reported experience measures by an anonymous e-survey with 11 statements based on a 1 to 6 Likert scale, and a final question measuring user satisfaction and loyalty through the Net Promoter Score (NPS). All PLWHIV with at least a clinical visit between January 1, 2020 and October 14, 2021 were invited. Of 5493 PLWHIV e-mailed, 1633 (30%) responded to the survey. The overall evaluation of clinical care was very favorable. The evaluation of the physical environment and facilities and the time spent in the waiting room received the lowest scores. According to the Net Promoter Score test results, 66% of respondents were willing to recommend this service, and 11% were not. Thus, monitoring patient reported experience measures in PLWHIV actively receiving outpatient care in our hospital allowed to identify the users' perception on quality of the care received, to determine the rate of satisfaction with the care, and to identify areas for improvement.

Sex-based epidemiological and immunovirological characteristics of people living with HIV in current follow-up at a tertiary hospital: a comparative retrospective study, Catalonia, Spain, 1982 to 2020.

BackgroundEpidemiological and immunovirological features of people living with HIV (PLWH) can vary by sex.AimTo investigate, particularly according to sex, characteristics of PLWH who consulted a tertiary hospital in Barcelona, Spain, in 1982-2020.MethodsPLWH, still in active follow-up in 2020 were retrospectively analysed by sex, age at diagnosis, age at data extraction (December 2020), birth place, CD4+ cell counts, and virological failure.ResultsIn total, 5,377 PLWH (comprising 828 women; 15%) were included. HIV diagnoses in women appeared to decrease from the 1990s, representing 7.4% (61/828) of new diagnoses in 2015-2020. From 1997, proportions of new HIV diagnoses from patients born in Latin America seemed to increase; moreover, for women born outside of Spain, the median age at diagnosis appeared to become younger than for those born in Spain, with significant differences observed in 2005-2009 and 2010-2014 (31 vs 39 years (p = 0.001), and 32 vs 42 years (p < 0.001) respectively), but not in 2015-2020 (35 vs 42 years; p = 0.254). Among women, proportions of late diagnoses (CD4+ cells/mm3 < 350) were higher than men (significantly in 2015-2020: 62% (32/52) vs 46% (300/656); p = 0.030). Initially, virological failure rates were higher in women than men, but they were similar in 2015-2020 (12% (6/52) vs 8% (55/659); p = 0.431). Women ≥ 50 years old represented 68% (564/828) of women actively followed up in 2020.ConclusionsWomen still have higher rates of late HIV diagnoses than men. Among currently-followed-up women, ≥ 50 year-olds, who need age-adapted care represent a high percentage. Stratifying PLWH by sex matters for HIV prevention and control interventions.

Determinants of Depressive Symptoms in People Living with HIV: Findings from a Population-Based Study with a Gender Perspective.

Depressive symptoms are common among people living with HIV (PLWH). The aim of this study was to identify the determinants of depressive symptoms in PLWH in Spain. A total of 1060 PLWH participated in this cross-sectional study and completed the Patient Health Questionnaire-9. The odds ratios for the presence of depressive symptoms were analyzed in a multivariable logistic regression model, including sociodemographic data, comorbidities, health-related behaviors, and social-environment-related variables. We found an overall prevalence of depressive symptoms of 21.42%; by subgroup, namely men, women, and transgender persons, prevalence was 18.13%, 32.81%, and 37.14%, respectively. Moreover, social isolation (OR = 1.05 [CI, 1.02-1.08]) and poor physical and mental quality of life (OR = 1.06 [CI, 1.02-1.09] and OR = 1.13 [CI, 1.09-1.17], respectively) were associated with depressive symptoms. As protective factors, we identified serodisclosure to more people (vs. none; OR = 0.39 [CI, 0.17-0.87]), satisfaction with social roles (OR = 0.86 [CI, 0.79-0.94]), better cognitive function (OR = 0.92 [CI, 0.89-0.95]), and sexualized drug use once in a lifetime (OR = 0.52 [CI, 0.29-0.93]). This study showed a high prevalence of depressive symptoms in PLWH, especially among women and transgender people. The association between psychosocial variables and depressive symptoms highlights the multidimensionality of the problem and identifies areas for intervention. This study found that the management of mental health issues is an area that needs to be improved and tailored to specific groups, with the aim of enhancing the well-being of PLWH.

Impact of HIV infection and integrase strand transfer inhibitors-based treatment on the gut virome.

Viruses are the most abundant components of the human gut microbiome with a significant impact on health and disease. The effects of human immunodeficiency virus (HIV) infection on gut virome has been scarcely analysed. Several studies suggested that integrase strand transfers inhibitors (INSTIs) are associated with a healthier gut. Thus, the objective of this work was to evaluate the effects of HIV infection and INSTIs on gut virome composition. 26 non-HIV-infected volunteers, 15 naive HIV-infected patients and 15 INSTIs-treated HIV-infected patients were recruited and their gut virome composition was analysed using shotgun sequencing. Bacteriophages were the most abundant and diverse viruses present in gut. HIV infection was accompanied by a decrease in phage richness which was reverted after INSTIs-based treatment. ß-diversity of phages revealed that samples from HIV-infected patients clustered separately from those belonging to the control group. Differential abundant analysis showed an increase in phages belonging to Caudoviricetes class in the naive group and a decrease of Malgrandaviricetes class phages in the INSTIs-treated group compared to the control group. Besides, it was observed that INSTIs-based treatment was not able to reverse the increase of lysogenic phages associated with HIV infection or to modify the decrease observed on the relative abundance of Proteobacteria-infecting phages. Our study describes for the first time the impact of HIV and INSTIs on gut virome and demonstrates that INSTIs-based treatments are able to partially restore gut dysbiosis at the viral level, which opens several opportunities for new studies focused on microbiota-based therapies.

IGF1R is a mediator of sex-specific metabolism in mice: Effects of age and high-fat diet.

Objective: We aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice. Methods: UBC-CreERT2, Igf1rfl/fl mutant mice were used to suppress IGF1R signaling in adult tissues by inducing postnatal generalized Igf1r deletion with tamoxifen. Animals were analyzed at two different ages: i) 13-weeks old young mice, and ii) 12-months old middle-aged mice. In addition, the effects of 10 weeks-long high-fat diet (HFD) were investigated in middle-aged mice. Results: Young IGF1R-deficient mice were insulin-resistant, with high IGF1, growth hormone (GH) and IGFBP3, as well as low IGFBP2 circulating levels. Males also presented increased triglycerides in liver. In contrast, middle-aged mice did not clearly show all of these alterations, suggesting possible compensatory effects. Middle-aged IGF1R-deficient male mice were able to counteract the negative effects induced by aging and HFD in adiposity, inflammation and glucose metabolism. A metabolic sexual dimorphism dependent on IGF1R was observed, especially in middle-aged mice. Conclusions: These results demonstrate that IGF1R is involved in metabolic homeostasis, with effects modulated by diet-induced obesity and aging in a sex dependent manner. Thus, IGF1R deficiency in mice is proposed as a useful tool to understand metabolic alterations observed in patients with IGF1R gene deletions.

Integrase Inhibitors Partially Restore Bacterial Translocation, Inflammation and Gut Permeability Induced by HIV Infection: Impact on Gut Microbiota.

INTRODUCTION: Human immunodeficiency virus (HIV) infection can be considered a chronic disease thanks to the extended use of antiretroviral treatment (ART). In this context, low-grade chronic inflammation related to gut microbiota (GM) dysbiosis and bacterial translocation (BT) among other factors has been observed despite the use of ART. In addition, different ART regimens have demonstrated differential impacts on GM. However, the role of novel integrase strand transfer inhibitors (INSTIs) has not been investigated yet. The aim of this study was to analyse the effects of INSTIs in first-line of treatment on markers of BT, inflammation, cardiovascular risk, gut permeability and GM composition and derived short-chain fatty acids. METHODS: Twenty-six non-HIV-infected volunteers and 30 HIV-infected patients (15 naïve and 15 under INSTIs regimen) were recruited. Blood samples were extracted to analyse biochemical parameters and markers of BT, inflammation, cardiovascular risk, gut permeability and bacterial metabolism. GM composition was analysed using 16S rRNA gene sequencing. RESULTS: Our results showed that HIV infection increased BT, inflammation, cardiovascular risk and gut permeability, whereas INSTIs counteracted these effects. Regarding GM, the reduction in bacterial richness induced by HIV infection was restored by INSTIs. Beta diversity revealed that HIV-infected people were separated from the control group independently of treatment. CONCLUSIONS: Current antiretroviral regimens based on INSTIs are able to reverse the impact of HIV infection on BT, systemic inflammation, gut permeability and bacterial diversity/richness, reaching similar levels to those observed in an uninfected/control population. These results suggest a protective role of INSTIs in disease progression, subsequent immune activation and in the development of future age-related complications such as cardiovascular events.

Corrigendum: ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study.

[This corrects the article DOI: 10.3389/fendo.2021.688071.].

ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study.

Coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme (ACE) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 patients with diverse degree of severity (33 asymptomatic or mildly symptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 in hypertensive patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 in dyslipidemic (p<0.05) and type 2 diabetic patients (p< 0.01). The association of G alleles with disease severity was adjusted for age, sex, BMI and number of comorbidities, suggesting that both the metabolic comorbidities and the G allele act synergistically on COVID-19 outcome. Although we did not find a direct association between serum ACE levels and COVID-19 severity, we found higher levels of ACE in the serum of patients with the GG genotype of rs4341 and rs4343 (p<0.05), what could explain the higher susceptibility to develop severe forms of the disease in patients with the GG genotype, in addition to hypertension and dyslipidemia. In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE could be predictive markers of severity of COVID-19 in those patients with hypertension, dyslipidemia or diabetes. The knowledge of these genetic data could contribute to precision management of SARS-CoV-2 infected patients when admitted to hospital.

A novel model of care for simplified testing of HBV in African communities during the COVID-19 pandemic in Spain.

Chronic hepatitis B virus (HBV) infection is a major public health threat for migrant populations in Spain and efforts to scale up testing are needed to reach the WHO elimination targets. The Hepatitis B Virus Community Screening and Vaccination in Africans (HBV-COMSAVA) study aims to use point-of-care testing and simplified diagnostic tools to identify, link to care, or vaccinate African migrants in Barcelona during the COVID-19 pandemic. From 21/11/20 to 03/07/2021, 314 study participants were offered HBV screening in a community clinic. Rapid tests for HBsAg screening were used and blood samples were collected with plasma separation cards. Patients received results and were offered: linkage to specialist care; post-test counselling; or HBV vaccination in situ. Sociodemographic and clinical history were collected and descriptive statistics were utilized. 274 patients were included and 210 (76.6%) returned to receive results. The HBsAg prevalence was 9.9% and 33.2% of people had evidence of past resolved infection. Overall, 133 required vaccination, followed by post-test counselling (n = 114), and linkage to a specialist (n = 27). Despite the COVID-19 pandemic, by employing a community-based model of care utilizing novel simplified diagnostic tools, HBV-COMSAVA demonstrated that it was possible to diagnose, link to care, and vaccinate African migrants in community-based settings.

Global health and the Royal College of Emergency Medicine: a cross-sectional survey of members and fellows.

BACKGROUND: There is growing interest in global health participation among emergency care doctors in the UK. The aim of this paper was to describe the demographics of members and fellows of the Royal College of Emergency Medicine involved in global health, the work they are involved in, as well as the benefits and barriers of this work. METHODS: We conducted a survey to include members and fellows of the Royal College of Emergency Medicine describing the context of their global health work, funding arrangements for global health work and perceived barriers to, and benefits of, global health work. RESULTS: The survey collected 1134 responses of which 439 (38.7%) were excluded. The analysis was performed with the remaining 695 (61.3%) responses. Global health involvement concentrated around South Asia and Africa. Work contexts were mainly direct clinical service (267, 38%), curriculum development (203, 29%) and teaching short courses (198, 28%). Activity was largely self-funded, both international (539, 78%) and from UK (516, 74%). Global health work was not reported to contribute to appraisal by many participants (294, 42.3%). Funding (443, 64%) and protected time (431, 62%) were reported as key barriers to global health productivity. DISCUSSION: Participants largely targeted specialty development and educational activities. Lack of training, funding and supported time were identified as barriers to development. Galvanising support for global health through regional networks and College support for attracting funding and job plan recognition will help UK-based emergency care clinicians contribute more productively to this field.

Immunological and virological efficacy of different antiretroviral regimens initiated during acute/recent HIV infection.

OBJECTIVES: Antiretroviral treatment (ART) during acute/recent HIV infection decreases transmission and optimizes immune recovery but the optimal ART-regimen in this setting is unknown. The objectives were to analyze the virological efficacy, immunological reconstitution and tolerability of different ART-regimens at 3 years after starting ART during acute/recent HIV infection. DESIGN: Retrospective cohort study of consecutive acutely/recently infected patients who started ART within 6 months postinfection. METHODS: We compared regimens based on protease-inhibitors (N = 28), integrase-strand-transfer-inhibitors (InSTI, N = 87) and nonnucleoside-reverse-transcriptase-inhibitors (N = 22). Virological suppression (viral load <50 copies/ml), immune reconstitution (CD4 T-cell count >900 cells/µl and CD4/CD8 ratio >1) and adverse events leading to ART discontinuation at 1 and 3 years were compared. RESULTS: Baseline characteristics were comparable among groups. Overall viral suppression at 1 (96%) and 3 years (99%) was comparable in all ART regimens and, InSTI group, comparable for dolutegravir and elvitegravir within InSTIs. CD4 T-cell counts at 1 year were comparable in all ART regimens. Overall proportion of patients reaching CD4 cell count more than 900 cells/µl and CD4/CD8 ratio more than 1 was 36% and 40% and 46% and 63% at 1 and 3 years, respectively with no differences among ART regimens. Starting ART during the earliest Fiebig stages (I-V vs. VI) was associated with higher rates of CD4 cell count more than 900 cells/µl at 3 years (P = 0.027). Discontinuation due to adverse events was more frequent with nonnucleoside-reverse-transcriptase-inhibitors compared with other ART classes. CONCLUSION: Viral suppression and immunological recovery were excellent, with no differences between ART regimens. Earlier ART initiation was associated with a higher proportion of long-term immunological recovery.

Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.

Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 & 18), and FT-A (administration of their own feces before developing obesity at weeks 17 & 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.

Prevalence, clinical characteristics and outcome of severe primary HIV-1 infection: A prospective cohort study.

BACKGROUND: Severe cases of primary HIV infection have been described in patients presenting with neurological involvement, AIDS defining events or other life-threatening events. These severe forms have not been fully studied. OBJECTIVES: To determine the prevalence and characteristics of severe PHI in a hospital-based cohort of primary HIV infection, and the response to the early initiation of antiretroviral therapy (ART) at 12 months. METHODS: Every patient with PHI attending Hospital Clínic of Barcelona (1997-2015) was evaluated. Severe PHI was defined using clinical, analytical and immunological criteria. Chi-squared test was used for categorical variables and Student's t-test for quantitative variables. RESULTS: 33% of 224 PHI patients (95% CI: 26.84%-39.16%) had a severe PHI. These patients had more symptoms, abnormal analytical parameters and hospital admissions. The severe PHI group had a significantly higher viral load although no differences were observed at 12 months in terms of viral suppression or CD4 count recovery. None died during PHI. CONCLUSIONS: Up to one third of patients in our cohort presented with a severe PHI, which was associated with higher hospitalization rates and higher plasma HIV RNA viral load. However, severe forms were not associated to a worse clinical, immunological or virological outcome at 12 months.

Short-term effects of direct-acting antiviral agents on inflammation and gut microbiota in hepatitis C-infected patients.

Liver damage is associated with gut dysbiosis. New direct-acting antiviral agents (DAAs) are able to eradicate hepatitis C virus (HCV) from the body. However, the short and medium-term effects of DAAs at gut level before advanced liver damage occurs have not been evaluated yet. Thus, we investigated the impact of HCV and DAAs on gut microbiota composition (GM) and systemic inflammation. To achieve this objective, twenty-three non HCV-infected controls and 22 HCV-infected patients were recruited. Only non-cirrhotic patients (fibrosis stage 0-3) were included to avoid the direct impact of cirrhosis and portal hypertension on gut. The HCV-groups were evaluated before the treatment, after completing DAAs treatment and after 3 months. Fecal bacterial 16S rDNA was ultrasequenced and several biochemical/metabolic/inflammatory parameters were quantified. HCV infection was accompanied by a significant increase in TNFα plasma levels. DAAs were able to reduce this increase, especially in lower fibrosis grades. HCV infection was not accompanied by dramatic changes in α-diversity and was not recovered after HCV negativization, although a complete restoration was observed in lower fibrosis degrees. Six phyla, 15 genera and 9 bacterial species resulted differentially abundant among the groups. These differences were almost blunted with lower fibrosis. In summary, neither the usage of DAAs nor 3 months in sustained viral response were able to counteract the changes induced by HCV at gut level. The partial restoration observed in inflammation and α-diversity was only observed in low fibrosis degrees. Thus, it is urgent to begin treatment with DAAs as soon as possible.

Characterization of gut microbiota composition in HIV-infected patients with metabolic syndrome.

The presence of metabolic syndrome (MS) per se or its separated components in HIV-infected patients contributes to an accelerated aging and increased cardiovascular risk. Gut microbiota (GM) dysbiosis has been linked with chronic inflammation associated with MS in a general non-infected population. However, no studies concerning GM have been performed in HIV-infected patients with MS. The aim of this study was to analyze bacterial translocation, inflammation, and GM composition in HIV-infected patients with and without MS. A total of 51 HIV-infected patients were recruited and classified according to the presence of MS (40 patients without MS and 11 with MS). Markers of bacterial translocation, inflammation, and cardiovascular risk were measured and GM was analyzed using 16S rRNA gene deep sequencing. No differences were observed among both HIV-infected groups in the bacterial translocation markers LBP and sCD14. A tendency to increase the inflammatory markers IL-6 (p = 0.069) and MCP-1 (p = 0.067) was observed in those patients suffering from MS. An increase in the cardiovascular risk markers PAI-1 (p = 0.007) and triglycerides/HDL cholesterol ratio (p < 0.0001) was also found in the MS group. No significant changes were observed at phylum level although a decrease in the abundance of seven genera and seven bacterial species, including some anti-inflammatory bacteria, was observed in HIV-infected patients with MS. To summarize, the presence of MS was not accompanied by major changes in GM, although the reduction observed in some anti-inflammatory bacteria may be clinically useful to develop strategies to minimize inflammation and its future deleterious consequences in these HIV-infected patients.

Agaricus bisporus supplementation reduces high-fat diet-induced body weight gain and fatty liver development

Obesity is a global epidemic characterized not only by excessive fat deposition but also by important complications such as nonalcoholic liver steatosis. Beneficial antiobesogenic effects have been described for some mushrooms. The current study aimed to demonstrate the protective effect of Agaricus bisporus (AB) supplementation against the metabolic alterations induced by high-fat-diet (HFD) feeding. Eight-week-old C57BL/6J mice were fed for 10 weeks with one of the following diets: (1) control diet (n = 7), (2) HFD (n = 7), (3) HFD supplemented with 5% AB (n = 9), and (4) HFD supplemented with 10% AB (n = 9). A pair-fed group was also included for the 10% AB group (n = 6). The impact of AB supplementation on food intake, body weight gain, and liver and fat pad weights was examined. Biochemical, histological, and molecular parameters were also analyzed. Dietary supplementation with 10% AB reduced the HFD-induced increase in body, epididymal, and mesenteric fat weights (p < 0.01, p < 0.05, and p < 0.05, respectively). Supplementation with AB also reduced liver damage in a dose-dependent manner (p < 0.01 and p < 0.001). This effect was confirmed by histological analysis that showed that liver steatosis was markedly reduced in mice fed with AB. The beneficial properties of 10% AB supplementation appear to be mediated through a decrease in food intake and via stimulation of mesenteric and hepatic free-fatty acid beta-oxidation, along with a decrease in epidydimal and hepatic expression of CD36. In conclusion, supplementation with AB prevents excessive body weight gain and liver steatosis induced by HFD consumption