Summary Objectives To analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004–2013). Methods Cox models and logistic ...regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS. Results Of 7165 new HIV diagnoses, 46.9% (CI95% :45.7–48.0) were LP, 240 patients died. First-year mortality was the highest (aHRLP.vs.nLP = 10.3CI95% :5.5–19.3); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2–3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7–3.1). First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004–05) to 39.4% (2012–13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women. Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.41.2–1.7); age (OR31–40.vs.<30 = 1.61.4–1.8, OR41–50.vs.<30 = 2.21.8–2.6, OR>50.vs.<30 = 3.62.9–4.4); behavior (ORInjectedDrugUse.vs.MSM = 2.82.0–3.8; ORHeterosexual.vs.MSM = 2.21.7–3.0); education (ORPrimaryEducation.vs.University = 1.51.1–2.0, ORLowerSecondary.vs.University = 1.31.1–1.5); and geographical origin (ORSub-Saharan.vs.Spain = 1.61.3–2.0, ORLatin-American.vs.Spain = 1.41.2–1.8). Conclusions LP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women.
Sensitivity, dynamic range and frequency tuning of the cochlea are attributed to amplification involving outer hair cell stereocilia and/or somatic motility. We measured acoustically and electrically ...elicited basilar membrane displacements from the cochleae of wild-type and TectaΔENT/ΔENT mice, in which stereocilia are unable to contribute to amplification near threshold. Electrically elicited responses from TectaΔENT/ΔENT mice were markedly similar to acoustically and electrically elicited responses from wild-type mice. We conclude that somatic, and not stereocilia, motility is the basis of cochlear amplification.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile ...in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response.
miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms.
A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response.
Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We assessed the effect of co-infection by hepatitis C virus (HCV) on immunological and virological response at 48 weeks from initiation of antiretroviral therapy (ART).We included patients from the ...Cohort of Spanish HIV Research Network (CoRIS) starting ART between January 2004 and November 2014, had at least 1 CD4 T-cell count and viral load measurements both in the previous 6 months and at 48 (±12) weeks from ART initiation, and HCV serology before ART initiation. We used linear regression for mean differences in CD4 T-cell count increase from ART initiation and logistic regression to estimate odds ratios for virological response.Of 12,239 patients by November 30, 2015, 5070 met inclusion criteria: 4382 (86.4%) HIV mono-infected and 688 (13.6%) HIV/HCV co-infected. Co-infected patients were more likely to have acquired HIV through injecting drugs use (57.4% vs. 1.1%), to be women, older, and Spanish, have a lower educational level, and having started ART with lower CD4 counts and acquired immunodeficiency syndrome. CD4 T-cell count increase at 48 weeks was 229.7 cell/μL in HIV-monoinfected and 161.9 cell/μL in HIV/HCV-coinfected patients. The percentages of patients achieving a virological response at 48 weeks were 87.0% and 78.3% in mono and coinfected patients, respectively. Multivariable analyses showed that at 48 weeks, coinfected patients increased 44.5 (95% confidence interval CI: 24.8-64.3) cells/μL less than monoinfected and had lower probability of virological response (odds ratio: 0.62; 95% CI: 0.44-0.88).HIV/HCV-coinfected patients have lower immunological and virological responses at 48 weeks from ART initiation than monoinfected patients.
Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic ...factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013.
Prospective multicenter cohort study.
Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE".
8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval CI, 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), age>50 years (1.78, 1.08-2.94), hepatitis C-coinfection (2.52, 1.38-4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20-5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01-4.66 for CD4 cell count between 200-350, both compared to CD4 cell count higher than 500) and concomitant CD4<200 cells/mL (2.22, 1.42-3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons.
NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the ...Spanish HIV/AIDS Network (CoRIS) during the years 2004–2017.
Methods
We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models.
Results
We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL.
Conclusions
The initial assessment of HIV‐infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations.
Resumen El interés por la simplificación surge de la necesidad de prescindir de los análogos de nucleósidos, por su toxicidad a largo plazo. Desde hace más de 10 años, en que surgieron los primeros ...estudios para analizar la seguridad y eficacia de esta estrategia con lopinavir/ritonavir, sigue despertando interés científico, clínico y económico. En el presente no hay un consenso en las recomendaciones; la interpretación de los resultados es discordante, y mientras algunos enfatizan el mayor riesgo de pérdida de la supresión viral, otros destacan que el posible repunte virológico con esta estrategia no se asocia con una pérdida de opciones terapéuticas ni emergencia de resistencias al inhibidor de proteasa potenciado con ritonavir. Este panorama determina las recomendaciones que se pueden hacer en la práctica clínica; casi todos los grupos están de acuerdo en que deben seleccionarse los pacientes candidatos a una simplificación con menos fármacos.
Abstract
In this pilot clinical trial, we evaluated rates of residual replication in persons without lamivudine resistance-associated mutations in proviral DNA population sequencing who switched to ...dolutegravir plus lamivudine. After 144 weeks, there was no signal of changes in residual viremia based on qualitative detection methods, irrespective of past lamivudine resistance.
Clinical Trials Registration. NCT03539224.
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