Role of maraviroc and/or rapamycin in the liver of IL10 KO mice with frailty syndrome.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Life expectancy of people with HIV on antiretroviral therapy in Spain.

OBJECTIVE: To estimate life expectancy of people with HIV (PWH) and describe causes of death. DESIGN: Antiretroviral therapy (ART)-naive adults from the CoRIS cohort starting ART in 2004-2019. METHODS: We calculated life expectancy at age 40 for men and women according to their ART initiation period, and stratified by transmission category, CD4 + cell count and AIDS diagnosis. We estimated life expectancy in 10-year age bands using life tables constructed from mortality rates, estimated through Poisson models. RESULTS: Life expectancy increased from 65.8 [95% confidence interval (CI) 65.0-66.6] in 2004-2008 to 72.9 (72.2-73.7) in 2014-2019 in men [general population comparators (GPC): 79.1 and 81.2 years, respectively] and from 65.8 (65.0-66.6) to 72.5 (71.8-73.3) in women (GPC: 84.9 and 86.4, respectively). Non-AIDS-related deaths accounted for 68% of deaths among men and 78% among women. Life expectancy was longer when starting ART with higher CD4 + cell counts and without AIDS. For men acquiring HIV through sex with men, starting ART in 2014-2019 without AIDS, life expectancy was 75.0 (74.2-75.7) with CD4 + cell count less than 200 cells/µl, rising to 78.1 (77.5-78.8) with CD4 + cell count at least 350 cells/µl. Corresponding figures were 70.1 (69.4-70.9) and 76.0 (75.3-76.7) for men acquiring HIV heterosexually (HTX) and 61.5 (60.7-62.3) and 69.0 (68.2-69.8) for those acquiring HIV through injection drug use (IDU). For women starting ART from 2014 without AIDS, life expectancy increased from 71.7 (71.0-72.4) to 77.3 (76.7-77.9) among HTX and from 63.7 (62.9-64.5) to 70.7 (70.0-71.5) among IDU. CONCLUSION: Our findings confirm the progressive improvement of life expectancy in PWH in Spain over the last decades, supporting the insurability of PWH on suppressive ART in our current setting and time.

Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.

HIV medical care interruption among people living with HIV in Spain, 2004-2020.

OBJECTIVE: We estimated the incidence rate of HIV medical care interruption (MCI) and its evolution over a 16-year-period, and identified associated risk factors among HIV-positive individuals from the Cohort of the Spanish AIDS Research Network in 2004-2020. DESIGN: We included antiretroviral-naive individuals aged at least 18 years at enrolment, recruited between January 1, 2004, and August 30, 2019, and followed-up until November 30, 2020. METHODS: Individuals with any time interval of at least 15 months between two visits were defined as having a MCI. We calculated the incidence rate (IR) of having at least one MCI and used multivariable Poisson regression models to identify associated risk factors. RESULTS: Of 15 274 individuals, 5481 (35.9%) had at least one MCI. Of those, 2536 (46.3%) returned to HIV care after MCI and 3753 (68.5%) were lost to follow-up at the end of the study period. The incidence rate (IR) of MCI was 7.2/100 person-years (py) [95% confidence interval (CI): 7.0-7.4]. The annual IR gradually decreased from 20.5/100 py (95% CI: 16.4-25.6) in 2004 to 4.9/100 py (95% CI: 4.4-5.5) in 2014, a slight increase was observed between 2015 and 2018, reaching 9.3/100 py (95% CI: 8.6-10.2) in 2019. Risk factors for MCI included younger age, lower educational level, having contracted HIV infection through injecting drug use or heterosexual intercourse, having been born outside of Spain, and CD4 + cell count >200 cell/µl, viral load <100 000 and co-infection with hepatitis C virus at enrolment. CONCLUSIONS: Around a third of individuals had at least one MCI during the follow-up. Identified predictors of MCI can help health workers to target and support most vulnerable individuals.

Identifying the needs of older people living with HIV (≥ 50 years old) from multiple centres over the world: a descriptive analysis.

BACKGROUND: Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings. METHODS: We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both. RESULTS: We organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life. CONCLUSIONS: Patients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction.

Predicting protein stability changes upon mutation using a simple orientational potential.

MOTIVATION: Structure-based stability prediction upon mutation is crucial for protein engineering and design, and for understanding genetic diseases or drug resistance events. For this task, we adopted a simple residue-based orientational potential that considers only three backbone atoms, previously applied in protein modeling. Its application to stability prediction only requires parametrizing 12 amino acid-dependent weights using cross-validation strategies on a curated dataset in which we tried to reduce the mutations that belong to protein-protein or protein-ligand interfaces, extreme conditions and the alanine over-representation. RESULTS: Our method, called KORPM, accurately predicts mutational effects on an independent benchmark dataset, whether the wild-type or mutated structure is used as starting point. Compared with state-of-the-art methods on this balanced dataset, our approach obtained the lowest root mean square error (RMSE) and the highest correlation between predicted and experimental ΔΔG measures, as well as better receiver operating characteristics and precision-recall curves. Our method is almost anti-symmetric by construction, and it performs thus similarly for the direct and reverse mutations with the corresponding wild-type and mutated structures. Despite the strong limitations of the available experimental mutation data in terms of size, variability, and heterogeneity, we show competitive results with a simple sum of energy terms, which is more efficient and less prone to overfitting. AVAILABILITY AND IMPLEMENTATION: https://github.com/chaconlab/korpm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy.

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right functioning of the body. An individual's circadian system is altered during aging, and this is related to numerous age-associated pathologies and other alterations that could contribute to the development of cancer. Nowadays, there is an increasing interest in understanding how circadian rhythms could be used in the treatment of cancer. Chronotherapy aims to understand the impact that biological rhythms have on the response to a therapy to optimize its action, maximize health benefits and minimize possible adverse effects. Clinical trials so far have confirmed that optimal timing of treatment with chemo or immunotherapies could decrease drug toxicity and increase efficacy. Instead, chronoradiotherapy seems to minimize treatment-related symptoms rather than tumor progression or patient survival. In addition, potential therapeutic targets within the molecular clock have also been identified. Therefore, results of the application of chronotherapy in cancer therapy until now are challenging, feasible, and could be applied to clinical practice to improve cancer treatment without additional costs. However, different limitations and variables such as age, sex, or chronotypes, among others, should be overcome before chronotherapy can really be put into clinical practice.

Local Normal Mode Analysis for Fast Loop Conformational Sampling.

We propose and validate a novel method to efficiently explore local protein loop conformations based on a new formalism for constrained normal mode analysis (NMA) in internal coordinates. The manifold of possible loop configurations imposed by the position and orientation of the fixed loop ends is reduced to an orthogonal set of motions (or modes) encoding concerted rotations of all the backbone dihedral angles. We validate the sampling power on a set of protein loops with highly variable experimental structures and demonstrate that our approach can efficiently explore the conformational space of closed loops. We also show an acceptable resemblance of the ensembles around equilibrium conformations generated by long molecular simulations and constrained NMA on a set of exposed and diverse loops. In comparison with other methods, the main advantage is the lack of restrictions on the number of dihedrals that can be altered simultaneously. Furthermore, the method is computationally efficient since it only requires the diagonalization of a tiny matrix, and the modes of motions are energetically contextualized by the elastic network model, which includes both the loop and the neighboring residues.

The circadian rhythm of viruses and its implications on susceptibility to infection.

INTRODUCTION: Circadian genes have an impact on multiple hormonal, metabolic, and immunological pathways and have recently been implicated in some infectious diseases. AREAS COVERED: We review aspects related to the current knowledge about circadian rhythm and viral infections, their consequences, and the potential therapeutic options. EXPERT OPINION: Expert opinion: In order to address a problem, it is necessary to know the topic in depth. Although in recent years there has been a growing interest in the role of circadian rhythms, many relevant questions remain to be resolved. Thus, the mechanisms linking the circadian machinery against viral infections are poorly understood. In a clear approach to personalized precision medicine, in order to treat a disease in the most appropriate phase of the circadian rhythm, and in order to achieve the optimal efficacy, it is highly recommended to carry out studies that improve the knowledge about the circadian rhythm.

Senotherapeutics in Cancer and HIV.

Cellular senescence is a stress-response mechanism that contributes to homeostasis maintenance, playing a beneficial role during embryogenesis and in normal adult organisms. In contrast, chronic senescence activation may be responsible for other events such as age-related disorders, HIV and cancer development. Cellular senescence activation can be triggered by different insults. Regardless of the inducer, there are several phenotypes generally shared among senescent cells: cell division arrest, an aberrant shape, increased size, high granularity because of increased numbers of lysosomes and vacuoles, apoptosis resistance, defective metabolism and some chromatin alterations. Senescent cells constitute an important area for research due to their contributions to the pathogenesis of different diseases such as frailty, sarcopenia and aging-related diseases, including cancer and HIV infection, which show an accelerated aging. Hence, a new pharmacological category of treatments called senotherapeutics is under development. This group includes senolytic drugs that selectively attack senescent cells and senostatic drugs that suppress SASP factor delivery, inhibiting senescent cell development. These new drugs can have positive therapeutic effects on aging-related disorders and act in cancer as antitumor drugs, avoiding the undesired effects of senescent cells such as those from SASP. Here, we review senotherapeutics and how they might affect cancer and HIV disease, two very different aging-related diseases, and review some compounds acting as senolytics in clinical trials.

Similar CD4/CD8 Ratio Recovery After Initiation of Dolutegravir Plus Lamivudine Versus Dolutegravir or Bictegravir-Based Three-Drug Regimens in Naive Adults With HIV.

Background: The initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR. Methods: We emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan-Meier method for survival curves. Results: We included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4/CD8 ratio >0.5, 15% achieved a ratio >1.0, and 6% achieved a ratio >1.5. GEE models yielded a similar risk of reaching a CD4/CD8 ratio >0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4/CD8 >1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4/CD8 >1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs. Conclusions: In this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4/CD8 normalization at 48 weeks.

DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks).

Brief: Real-world data in naïve HIV-1 patients demonstrate that dolutegravir plus lamivudine in a multiple tablet regimen is effective, safe, and satisfactory; it causes moderately increasing weight and abdominal circumference and is administrable on a test-and-treat strategy. Background: Our objectives were to determine the real-life effectiveness and safety of DT with dolutegravir (50 mg/QD) plus lamivudine (300 mg/QD) in a multiple-tablet regimen (MTR) in naïve PLHIV followed up for 48 weeks and to evaluate the compliance and satisfaction of patients. Material and methods: An open, single-arm, multicenter, non-randomized clinical trial from May 2019 through September 2020 with a 48-week follow-up. Results: The study included 88 PLHIV patients (87.5% male) with a mean age of 35.9 years; 76.1% were MSM patients. The mean baseline CD4 was 516.4 cells/uL, with a viral load (VL) of 4.49 log10, and 11.4% were in the AIDS stage. DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I + E138A, and V108I); 12.5% were lost to follow-up. At week 48, 86.3% had VL < 50 cop/uL by intention-to-treat analysis and 98.7% by per-protocol (PP) analysis. Virological failure (VF) was recorded in 1.1%, with no resistance mutation. One blip was detected in 5.2% without VF. Three reported anxiety, dizziness, and cephalgia, respectively, at week 4 and one reported insomnia at week 24; none reported adverse events at week 48. The mean weight was 4 kg higher at 48 weeks (p = 0.0001) and abdominal circumference 3 cm larger at 24 weeks (p = 0.022). No forgetfulness occurred in 98.7% of patients. Patient satisfaction was 90/100 at 4, 24, and 48 weeks. Conclusion: Real-world data demonstrate that dolutegravir plus lamivudine in MTR is effective, safe, and satisfactory, moderately increasing weight and abdominal circumference and administrable on a test-and-treat strategy.

Elevated levels of serum CDCP1 in individuals recovering from severe COVID-19 disease.

BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.

Executive summary of the consensus document of the HIV quality of care indicators. GESIDA updated.

This article aims to review the main information taken into account for the update of the GESIDA PLWH quality indicators. Finally 54 indicators covering a major part of the clinical activity in PLWH were defined. They evaluate the detection and diagnosis of PLWH, their follow-up and prevention, initiation and adaptation of ART, women's specific aspects, comorbidities, hospitalization, and AIDS-related mortality.

Executive summary of the consensus document of the HIV quality of care indicators. GESIDA updated / Resumen ejecutivo del documento actualizado del consenso de los indicadores de Calidad de GESIDA

This article aims to review the main information taken into account for the update of the GESIDA PLWH quality indicators.Finally 54 indicators covering a major part of the clinical activity in PLWH were defined.They evaluate the detection and diagnosis of PLWH, their follow-up and prevention, initiation and adaptation of ART, women's specific aspects, comorbidities, hospitalization, and AIDS-related mortality.

Este artículo tiene como objetivo revisar la principal información que se tuvo en cuenta para la actualización de los indicadores de calidad de PVV de GESIDA.Finalmente, se definieron 54 indicadores que cubren la mayor parte de la actividad clínica en PVV. Los indicadores evalúan la detección y el diagnóstico de los PVV, su seguimiento y prevención, la iniciación y adherencia al TAR, aspectos específicos de la mujer, comorbilidades, hospitalización y mortalidad relacionada con el sida.

Weight changes after antiretroviral therapy initiation in CoRIS (Spain): a prospective multicentre cohort study.

INTRODUCTION: Weight gain after starting antiretroviral therapy (ART) is a major problem that can increase morbidity. Our main objective was to evaluate the effects of initial ART on weight change in a large prospective cohort of HIV-positive individuals. METHODS: This was a prospective cohort study of 13,198 subjects included in the Spanish HIV Research Network (CoRIS) between January 2004 and November 2018. We included subjects who started triple ART and achieved HIV RNA suppression within 48 weeks. We fitted linear mixed models adjusted for potential confounders to compare longitudinal changes in weight. We used Cox proportional-hazard models to compare treatment groups' times to transition to a higher body mass index (BMI) category. RESULTS: We analysed data from a total of 1631 individuals resulting in 14,965 persons/years and 14,085 observations. Individuals retained in the final multivariable model were representative of the overall cohort. NNRTI-based first-line ART was associated with a lower average weight gain compared to PI- (+0.7 kg per year, 95% CI 0.5 to 1.0, p < 0.001) and INSTI-based (+0.9 kg per year, 95% CI 0.7 to 1.1, p < 0.001) regimens. Individuals starting ART with TAF+FTC had greater weight gain than those receiving TDF+FTC (+0.8 kg per year, 95% CI 0.3 to 1.4, p = 0.004). Women and black persons presented a greater weight gain than men and non-black individuals. Differences in weight trajectories were driven mainly by changes during the first year of ART. The NNRTI group was less likely to transition from normal weight to overweight than the PI (aHR 1.48, 95% CI 1.18 to 1.85) and INSTI groups (aHR 1.30, 95% CI 1.03 to 1.64). PIs but not INSTIs were associated with a higher rate of overweight-to-obesity shift (aHR 2.17, 95% CI 1.27 to 3.72). No differences were found among INSTIs in the transition to a higher BMI category. CONCLUSIONS: INSTI- and PI-based first-line ARTs are associated with greater weight gain compared to NNRTI-based ART. Within the NRTIs, TAF+FTC was most strongly associated with weight gain. This heterogeneous effect of ART on body weight could affect the long-term risk of some non-communicable diseases.

Pulmonary long-term consequences of COVID-19 infections after hospital discharge.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) survivors are reporting residual abnormalities after discharge from hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. This study aimed to describe lung function in patients recovering from COVID-19 hospitalization and to identify biomarkers in serum and induced sputum samples from these patients. METHODS: Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalization. Patients' epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardized 6-minute walk test (6MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. RESULTS: A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% of patients (47/100). CT was normal in 48% of patients (48/100). Lung function was normal forced expiratory volume in one second (FEV1) ≥80%, forced vital capacity (FVC) ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide (DLCO) ≥80% in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p < 0.0001) and a lower serum lactate dehydrogenase level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 cases during hospital stay. CONCLUSIONS: A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases.

Impact of HIV infection on aging and immune status.

Introduction: Thanks to antiretroviral therapy (ART), persons living with HIV (PLWH), have a longer life expectancy. However, immune activation and inflammation remain elevated, even after viral suppression, and contribute to morbidity and mortality in these individuals.Areas covered: We review aspects related to immune activation and inflammation in PLWH, their consequences, and the potential strategies to reduce immune activation in HIV-infected individuals on ART.Expert opinion: When addressing a problem, it is necessary to thoroughly understand the topic. This is the main limitation faced when dealing with immune activation and inflammation in PLWH since there is no consensus on the ideal markers to evaluate immune activation or inflammation. To date, the different interventions that have addressed this problem by targeting specific mediators have not been able to significantly reduce immune activation or its consequences. Given that there is currently no curative intervention for HIV infection, more studies are necessary to understand the mechanism underlying immune activation and help to identify potential therapeutic targets that contribute to improving the life expectancy of HIV-infected individuals.

Psychological distress in women and men living with HIV in Spain: a cross-sectional telephone survey.

BACKGROUND: Psychological distress includes a broader range of experiences, varying from less severe symptoms of depression and anxiety to severe psychiatric disease. Global estimates for depression and anxiety in 2017 were 3.4% and 3.8%, respectively. While for people living with HIV, global estimates were 16% and 33%, respectively. OBJECTIVE: We aimed to determine the prevalence of psychological distress by gender and associated characteristics in patients living with HIV. METHODS: A cross-sectional study was conducted within the Spanish HIV Research Network CoRIS. Participants were interviewed by telephone between 2010 and 2014 about their psychological distress, sociodemographics, drug consumption, self-perceived health and combined antiretroviral therapy (cART) adherence. Laboratory tests and medical history details were collected from CoRIS. Logistic regression was used to identify characteristics associated with psychological distress. FINDINGS: We interviewed 99 women and 464 men, both living with HIV. A greater proportion of women (51, 51.5%) reported psychological distress than men (179, 38.6%; p<0.01). Non-adherence to cART (OR 4.6 and 2.3, 95% CI 1.4‒15.1 and 1.3‒4.2) and non-use of cART (8.4 and 1.8, 2.2‒32.4 and 1.1‒2.8) were related to psychological distress in women and men, respectively. Spending little time in leisure-based physical activity was related to psychological distress in women (3.1, 1.1‒9.0). Living alone (2.0, 1.3‒3.0) and being unemployed (2.3, 1.4‒3.6) were related to psychological distress in men. CONCLUSIONS AND CLINICAL IMPLICATIONS: As people living with HIV have a high prevalence of psychological distress, their regular screening appointments should include psychological assessment. A gendered approach is needed to detect and manage psychological distress.

Implications of maraviroc and/or rapamycin in a mouse model of fragility.

BACKGROUND: As age increases, the risk of developing fragility also increases. Improving the knowledge of frailty could contribute to maintaining the functional ability of elderly people. Interleukin (IL)-10 homozygous knockout mice (IL-10tm/tm [IL10KO]) constitute an excellent tool for the study of frailty. Because patients with frailty demonstrate an overexpression of CCR5, rapamycin (RAPA) and/or maraviroc (MVC), two molecules able to decrease CCR5 expression, were evaluated. RESULTS: Muscle myostatin was reduced in all the therapeutic groups but the MVC group (p <0.001 for RAPA and MVC-RAPA) and in serum samples (p <0.01 for all the groups). Serum CK levels were also significantly lower in MVC and RAPA groups (p <0.01 in both cases). Lower AST levels were observed in all the therapeutic groups (p <0.05 for all of them). The apoptotic effector caspase-3 was significantly lower in MVC and RAPA groups (p<0.05 in both cases). Combined treatment with MVC-RAPA showed a synergistic increase in p-AKT, p-mTOR and SIRT1 levels. CONCLUSIONS: MVC and RAPA show a protective role in some factors involved in frailty. More studies are needed to prove their clinical applications. MATERIAL AND METHODS: Eighty male homozygous IL10KOs were randomly assigned to one of 4 groups (n= 20): i) IL10KO group (IL10KO); ii) IL10KO receiving MVC in drinking water (MVC group), iii) IL10KO receiving RAPA in drinking water (RAPA group), and finally, iv) MVC-RAPA group that received MVC and RAPA in drinking water. Blood and muscle samples were analysed. Survival analysis, frailty index calculation, and functional assessment were also performed.