Mitochondrial Haplogroups and Weight Gain After Initiating ART in Patients with HIV.

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1,019 treatment-naïve persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 Kg and 0.98 Kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.

Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions.

Objectives: We previously found that the pluripotency factor OCT4 is reactivated in smooth muscle cells (SMC) in human and mouse atherosclerotic plaques and plays an atheroprotective role. Loss of OCT4 in SMC in vitro was associated with decreases in SMC migration. However, molecular mechanisms responsible for atheroprotective SMC-OCT4-dependent effects remain unknown. Methods: Since studies in embryonic stem cells demonstrated that OCT4 regulates long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), making them candidates for OCT4 effect mediators, we applied an in vitro approach to investigate the interactions between OCT4-regulated lncRNAs, mRNAs, and miRNAs in SMC. We used OCT4 deficient mouse aortic SMC (MASMC) treated with the pro-atherogenic oxidized phospholipid POVPC, which, as we previously demonstrated, suppresses SMC contractile markers and induces SMC migration. Differential expression of lncRNAs, mRNAs, and miRNAs was obtained by lncRNA/mRNA expression array and small-RNA microarray. Long non-coding RNA to mRNA associations were predicted based on their genomic proximity and association with vascular diseases. Given a recently discovered crosstalk between miRNA and lncRNA, we also investigated the association of miRNAs with upregulated/downregulated lncRNA-mRNA pairs. Results: POVPC treatment in SMC resulted in upregulating genes related to the axon guidance and focal adhesion pathways. Knockdown of Oct4 resulted in differential regulation of pathways associated with phagocytosis. Importantly, these results were consistent with our data showing that OCT4 deficiency attenuated POVPC-induced SMC migration and led to increased phagocytosis. Next, we identified several up- or downregulated lncRNA associated with upregulation of the specific mRNA unique for the OCT4 deficient SMC, including upregulation of ENSMUST00000140952-Hoxb5/6 and ENSMUST00000155531-Zfp652 along with downregulation of ENSMUST00000173605-Parp9 and, ENSMUST00000137236-Zmym1. Finally, we found that many of the downregulated miRNAs were associated with cell migration, including miR-196a-1 and miR-10a, targets of upregulated ENSMUST00000140952, and miR-155 and miR-122, targets of upregulated ENSMUST00000155531. Oppositely, the upregulated miRNAs were anti-migratory and pro-phagocytic, such as miR-10a/b and miR-15a/b, targets of downregulated ENSMUST00000173605, and miR-146a/b and miR-15b targets of ENSMUST00000137236. Conclusion: Our integrative analyses of the lncRNA-miRNA-mRNA interactions in SMC indicated novel potential OCT4-dependent mechanisms that may play a role in SMC phenotypic transitions.

Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis.

BACKGROUND AND AIMS: We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response with direct-acting antivirals in patients coinfected with HIV/HCV with advanced fibrosis or cirrhosis. APPROACH AND RESULTS: A total of 1300 patients who achieved sustained viral response with direct-acting antivirals from 2014 to 2017 in Spain were included: 1145 with compensated advanced chronic liver disease (384 advanced fibrosis and 761 compensated cirrhosis) and 155 with decompensated cirrhosis. The median follow-up was 40.9 months. Overall, 85 deaths occurred, 61 due to non-liver non-AIDS-related causes that were the leading cause of death across all stages of liver disease. The incidence (95% CI) of decompensation per 100 person-years (py) was 0 in patients with advanced fibrosis, 1.01 (0.68-1.51) in patients with compensated cirrhosis, and 8.35 (6.05-11.53) in patients with decompensated cirrhosis. The incidence (95% CI) of HCC per 100 py was 0.34 (0.13-0.91) in patients with advanced fibrosis, 0.73 (0.45-1.18) in patients with compensated cirrhosis, and 1.92 (1.00-3.70) per 100 py in patients with decompensated cirrhosis. Prognostic factors for decompensation in patients with compensated advanced chronic liver disease included serum albumin, liver stiffness measurement (LSM), and fibrosis 4. In this population, LSM and LSM-based posttreatment risk stratification models showed their predictive ability for decompensation and HCC. CONCLUSIONS: Non-liver non-AIDS-related events were the leading causes of morbidity and mortality after direct-acting antiviral cure among coinfected patients with advanced fibrosis/cirrhosis. Among those with compensated advanced chronic liver disease, baseline LSM and posttreatment LSM-based models helped to assess decompensation and HCC risk.

Estimated Respiratory Syncytial Virus-Related Hospitalizations and Deaths Among Children and Adults in Spain, 2016-2019.

INTRODUCTION: Respiratory syncytial virus (RSV) causes a substantial disease burden among infants. In older children and adults, incidence is underestimated due to nonspecific symptoms and limited standard-of-care testing. We aimed to estimate RSV-attributable hospitalizations and deaths in Spain during 2016-2019. METHODS: Nationally representative hospitalization and mortality databases were obtained from the Ministry of Health and the National Statistical Office. A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends and viral activity, while allowing for potential overdispersion. RESULTS: In children, the RSV-attributable respiratory hospitalization incidence was highest among infants aged 0-5 months (3998-5453 cases/100,000 person-years, representing 72% of all respiratory hospitalizations) and decreased with age. In 2019, estimated rates in children 0-5, 6-11, 12-23 months and 6-17 years were approximately 1.3, 1.4, 1.5, and 6.5 times higher than those based on standard-of-care RSV-specific codes. In adults, the RSV-attributable cardiorespiratory hospitalization rate increased with age and was highest among persons ≥ 80 years (1325-1506 cases/100,000, 6.5% of all cardiorespiratory hospitalizations). In 2019, for persons aged 18-49, 50-59, 60-79, and ≥ 80 years, estimated rates were approximately 8, 6, 8, and 16 times higher than those based on standard-of-care RSV-specific codes. The RSV-attributable cardiorespiratory mortality rate was highest among ≥ 80 age group (126-150 deaths/100,000, 3.5-4.1% of all cardiorespiratory deaths), when reported mortality rate ranged between 0 and 0.5/100,000. CONCLUSIONS: When accounting for under-ascertainment, estimated RSV-attributable hospitalizations were higher than those reported based on standard-of-care RSV-specific codes in all age groups but particularly among older children and older adults. Like other respiratory viruses, RSV contributes to both respiratory and cardiovascular complications. Efficacious RSV vaccines could have a high public health impact in these age and risk groups.

Impact of a longitudinal course on medical professionalism on the empathy of medical students.

OBJECTIVE: Medical education should enhance empathy. We examined, using self-assessment instruments and standardized patients (SPs), the impact on empathy, of a multi-year intervention (years 4-6 of medical training) that uses reflective learning approaches. METHODS: 241 final-year medical students participated; 110 from the 2018 graduation class (non-intervention group) and 131 from the 2019 graduation class (intervention group). Participants completed two self-reported empathy questionnaires - the Jefferson Scale of Empathy-Students (JSE-S) and the Interpersonal Reactivity Index (IRI) - and a personality questionnaire, the NEO Five-Factor Inventory. Additionally, SPs in a simulated station assessed participants' empathy with two patient-reported instruments: the Consultation and Relational Empathy (CARE) scale and the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE). RESULTS: Empathy scores were significantly higher in the intervention group compared to the non-intervention group when assessed by the SP (p < 0.001). No differences were found in self-reported questionnaires between the two groups. CONCLUSION: A longitudinal, multi-year reflection-based intervention enhanced empathy amongst medical students as assessed by SPs, but not when assessed by student self-reported measures. PRACTICE IMPLICATIONS: Multi-year reflective learning interventions during clinical training nurture empathy in medical students. Assessments completed by SPs or patients may enhance the evaluation of empathy.

Antibodies to SARS-CoV2 induced by vaccination and infection correlate with protection against the infection.

The COVID-19 pandemic remained worldwide for almost three years, but little is known about the dynamics of humoral immune response to the third dose over time and its protection from infection. Our aim was to assess the humoral immune response after the third dose of the different vaccines administered to SARS-CoV-2 naive and previously infected individuals, and its correlation with protection in an academic community. For each person studied (185), three blood samples were taken between December 2021 and July 2022, one month apart. Anti-S antibodies were quantified by ELISA, while anti-N antibody levels were determined by ECLIA. Most of the participants had received two doses of viral vector-based, mRNA-based and virus-inactivated vaccines. Although anti-N antibody levels revealed that 80% of the individuals had been exposed to the virus before or during the study, only 42% reported having been diagnosed. When anti-S IgG levels were measured 3-5 months after the second dose of any vaccine, they were higher in those previously infected individuals. The same results were observed for anti-N IgG levels in those who received 2 doses of the virus-inactivated vaccine. When analyzing the dynamics of anti-S antibodies we observed that, although positive IgG antibody levels were detected 5-6 months after the second dose administration, those observed 30-60 days after the third dose were significantly higher and remained so for at least 8 months. Higher levels of anti-S IgG antibodies at the first sampling were associated with a lower incidence of subsequent infection. The same association was seen in people who received the booster compared with those who received two doses. This study provides further evidence that anti-S IgG antibodies remained at high levels over time, and both anti-S levels and the third dose of anti-SARS-CoV-2 vaccine correlate with protection against the infection. It also shows that infection acts as a booster of immunization, increasing levels of both anti-N and anti-S IgG.

Comparative study of the etiology of nosocomial bacteremic pneumonia in ventilated and non-ventilated patients: a 10-year experience in an institution.

IMPORTANCE: This study on bacteremic nosocomial pneumonia (bNP) demonstrates the importance of this condition both in patients undergoing and not undergoing mechanical ventilation. Staphylococcus aureus, Enterobacterales, and non-fermenting Gram-negative bacilli are all causative agents in ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP), with a predominance of S. aureus in HAP and of Pseudomonas aeruginosa in VAP. Mortality in this condition is very high. Therefore, new therapeutic and preventive approaches should be sought.

Predictive plasma biomarkers of long-term increase in hepatic steatosis index after HCV eradication in HIV/HCV-coinfected patients.

Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4-1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients.

Pneumocystis jirovecii Pneumonia Diagnostic Approach: Real-Life Experience in a Tertiary Centre.

Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients entails high mortality and requires adequate laboratory diagnosis. We compared the performance of a real time-PCR assay against the immunofluorescence assay (IFA) in the routine of a large microbiology laboratory. Different respiratory samples from HIV and non-HIV-infected patients were included. The retrospective analysis used data from September 2015 to April 2018, which included all samples for which a P. jirovecii test was requested. A total of 299 respiratory samples were tested (bronchoalveolar lavage fluid (n = 181), tracheal aspirate (n = 53) and sputum (n = 65)). Forty-eight (16.1%) patients fulfilled the criteria for PJP. Five positive samples (10%) had only colonization. The PCR test was found to have a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96%, 98%, 90% and 99%, compared to 27%, 100%, 100% and 87%, for the IFA, respectively. PJ-PCR sensitivity and specificity were >80% and >90% for all tested respiratory samples. Median cycle threshold values in definite PJP cases were 30 versus 37 in colonized cases (p < 0.05). Thus, the PCR assay is a robust and reliable test for the diagnosis PJP in all respiratory sample types. Ct values of ≥36 could help to exclude PJP diagnosis.

PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study.

BACKGROUND: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. METHODS: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). RESULTS: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). CONCLUSIONS: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

BACKGROUND: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). METHODS: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. RESULTS: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). CONCLUSIONS: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.

Pregnancy Outcomes Among Perinatally HIV-Infected Women in Spain.

BACKGROUND: An increasing number of women living with perinatally acquired HIV are reaching adulthood and becoming pregnant. Achieving viral suppression is challenging in this population frequently exposed to numerous antiretroviral regimens. This study describes the long-term outcomes of pregnant women living with perinatally acquired HIV in Spain. METHODS: Descriptive, retrospective, multicenter study of the women living with perinatally acquired HIV who gave birth between January 2000 and December 2019 in Madrid. Epidemiological, clinical, and HIV-related data were collected from the first delivery to the end of the study period, including antiretroviral therapy, prevention strategies, and outcomes. RESULTS: Sixty-three live births in 33 women were included. The mean number of pregnancies per women was 1.9 (range: 1-6). At first delivery, women's median age was 20 years (interquartile range: 18-23), 11 (33.3%) had been previously diagnosed with AIDS and 6 (18%) with mental health disorders. Forty percent became pregnant unsuppressed, whereas 81% achieved viral suppression at delivery. Treatment interruptions were common after delivery, as were losses to follow-up, with no positive effect of pregnancy on retention to care or the immune virological situation. Five women (15%) experienced a new AIDS event, and there were 2 deaths (6%) during follow-up. There was 1 case of mother-to-child transmission in a nonadherent woman in whom preventive measures could not be implemented. CONCLUSIONS: Pregnancy in this unique population of women living with perinatally acquired HIV poses particular challenges. Specific strategies, including a multidisciplinary approach, are needed to minimize perinatal transmission risks and improve outcomes during the postpartum period.

Non-invasive tests for clinically significant portal hypertension after HCV cure.

BACKGROUND & AIMS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting. METHODS: A total of 418 patients with pre-treatment HVPG ≥6 mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort). RESULTS: HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r = 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843-0.926). Post-treatment LSM <12 kPa & PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25 kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12 kPa & PLT >150 G/L criteria. In patients with post-treatment LSM ≥25 kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%). CONCLUSIONS: NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12 kPa & PLT>150 G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25 kPa require surveillance/treatment. LAY SUMMARY: Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.

Progress in the quality of care for newly diagnosed people with HIV in Spain (2004-2019).

BACKGROUND: We monitored the quality of care for newly diagnosed people with HIV (PWH) in Spain, including linkage to care within 1 month of HIV diagnosis (LC-1Mo) and viral suppression within 3 months of HIV diagnosis (VS-3Mo). METHODS: Longitudinal study based on The Cohort of the Spanish AIDS Research Network (CoRIS). We used logistic regression stratified by year of HIV diagnosis (2004-2013 and 2014-2019) to assess differences by sex, country of origin, HIV risk group, age, prior AIDS, HIV Viral Load, and CD4 cell count. RESULTS: The final analysis included 13,632 PWH: males 85%, men having sex with men (MSM) 61%, median age 35 years. LC-1Mo increased from 42% (95% CI, 38%-46%) in 2004 to 80% (95% CI, 77%-83%) in 2019 (P < 0.001). Median CD4+ cell counts at ART initiation increased from <250/mm3 in 2004-2005 to >350/mm3 since 2012 (P < 0.001). The percentage of initial regimens based on integrase strand transfer inhibitors (INSTI) increased from 3% in 2004 to >70% from 2016 onwards (P < 0.001). VS-3Mo increased from 6% (95% CI, 4%-8%) in 2004 to 45% (95% CI, 41%-49%) in 2019 (P < 0.001). Worst results for LC-1Mo were found among PWH acquiring HIV by injection drug use and those born in Latin American Countries across all the study period. CONCLUSION: Care indicators have improved among newly diagnosed PWH in Spain over the last 15 years. Removal of CD4 cell counts limitations, and probably the increasing use of INSTI-based regimens was decisive for the progress made.

miRNA/mRNA co-profiling identifies the miR-200 family as a central regulator of SMC quiescence.

miRNAs are versatile regulators of smooth muscle cell (SMC) fate and behavior in vascular development and disease. Targeted loss-of-function studies have established the relevance of specific miRNAs in controlling SMC differentiation or mediating phenotypic modulation. Our goal was to characterize SMC miRNAome and its contribution to transcriptome changes during phenotypic modulation. Small RNA sequencing revealed that dedifferentiation led to the differential expression of over 50 miRNAs in cultured SMC. miRNA/mRNA comparison predicted that over a third of SMC transcript expression was regulated by differentially expressed miRNAs. Our screen identified the miR-200 cluster as highly downregulated during dedifferentiation. miR-200 maintains SMC quiescence and represses proliferation, migration, and neointima formation, in part by targeting Quaking, a central SMC phenotypic switching mediator. Our study unraveled the substantial contribution of miRNAs in regulating the SMC transcriptome and identified the miR-200 cluster as a pro-quiescence mechanism and a potential inhibitor of vascular restenosis.