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1.
Sci Rep ; 9(1): 15722, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673011

RESUMO

A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4+ T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4+ T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4+ T-cell counts, immune recovery status and the absolute increment of CD4+ T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4+ T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects.

2.
Expert Opin Drug Metab Toxicol ; 15(10): 787-802, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31512529

RESUMO

Introduction: Drug-drug interactions (DDI) between antiretroviral drugs and drugs for the treatment of metabolic disturbances in people living with human immunodeficiency virus (HIV) (PLWH) have represented a problem of paramount importance in the recent times. The problem has been mainly driven by sharing common metabolizing pathways. This problem has classically been worsened by the frequent use of pharmacokinetic boosters to enhance protease inhibitors and some integrase inhibitors plasma levels. Areas covered: This article focuses on the interactions between antiretroviral drugs and those drugs used to treat metabolic disturbances which frequently appear in PLWH. These include dyslipidemia, diabetes mellitus, hyperuricemia, and finally, drugs for the treatment of overweight and clinical obesity. References from PubMed, Embase, or Web of Science, among others, were reviewed. Expert opinion: The advent of safer drugs, in terms of DDI, in the antiretroviral and the metabolic field,such as non-boosted antiretrovirals and drugs with divergent metabolizing paths. Besides, learning by the caregivers on how to decrease and manage DDI, together with the extensive use of online updated DDI databases, has undoubtedly minimized the problem. The foreseeable increase in the burden of HIV-associated comorbidities and their associated treatments anticipates further complexities in the management of DDI in PLWH.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Interações de Medicamentos , Infecções por HIV/complicações , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Humanos , Doenças Metabólicas/etiologia , Doenças Metabólicas/fisiopatologia
3.
Lancet Infect Dis ; 19(8): e284-e294, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31053493

RESUMO

Meningococcal disease was first clinically characterised by Gaspard Vieusseux in 1805, and its causative agent was identified by Anton Weichselbaum in 1887, who named it Diplococcus intracellularis menigitidis. From the beginning, the disease was dreaded because of its epidemic nature, predilection for previously healthy children and adolescents, and high mortality. In the last decade of the 19th century, the concept of serum therapy for toxin-related bacterial diseases was identified. This concept was applied to meningococcal disease therapy, in an independent way, by Wilhelm Kolle, August von Wasserman, and Georg Jochmann in Germany, and Simon Flexner in the USA, resulting in the first successful approach for the treatment of meningococcal disease. During the first three decades of the 20th century, serum therapy was the standard treatment for meningococcal disease. With the advent of sulphamides first and then antibiotics, serum therapy was abandoned. The great challenges that infectious diseases medicine is facing and the awaiting menaces in the future in terms of increasing antibiotic resistance, emergence of new pathogens, and re-emergence of old ones without effective therapy, make passive immunotherapy a promising tool. Acknowledging the achievements of our predecessors might teach us some lessons to bring light to our future.

4.
Nefrologia ; 39(5): 497-505, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31027896

RESUMO

BACKGROUND: The use of combination antiretroviral therapy has led to dramatic improvements in the life expectancy of HIV-infected persons. As result, the HIV population is aging and increasingly facing illnesses typically seen in the elderly, such as chronic kidney disease (CKD). METHODS: A retrospective longitudinal study was conducted using data from years 2010 and 2014 in all HIV-infected persons enrolled at the Spanish VACH cohort. We analyzed the prevalence and the predictive factors for developing CKD (estimated glomerular filtration rate, eGFR<60mL/min/1.73m2). RESULTS: The CKD prevalence at baseline was 456/8968, 5.1% [4.6-5.6%]. Of 8512 HIV-positive individuals examined without CKD at baseline (73.7% male, median age 44 years-old), 2.15% developed CKD (eGFR<60mL/min/1.73m2). The odds ratios [95%CI] for the independent predictive factors identified were gender (male) 0.54 [0.39-0.75], age (per year) 1.08 [1.07-1.10], AIDS diagnosis 1.40 [1.03-1.91], protease inhibitor-based regimens 1.49 [1.10-2.02], hypertension 1.37 [0.94-1.99], diabetes 1.84 [1.33-2.55] and history of cardiovascular events 1.66 [0.96-2.86]. CONCLUSION: The prevalence and risk factors for CKD and its progression are high in the VACH cohort. Thus, preventive measures such as control of hypertension, diabetes and obesity, as well as efforts for avoiding exposure to nephrotoxic drugs, including some antiretrovirals, are warranted in this aging HIV population.

5.
Expert Rev Clin Pharmacol ; 12(5): 389-396, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31017494

RESUMO

INTRODUCTION: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut. Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies. Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inflamação/tratamento farmacológico , Doença Crônica , Quimioterapia Combinada , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Sobrevida , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
6.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 37(3): 151-159, mar. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-181298

RESUMO

Background: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Methods: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. Results: In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC + RAL (PR). The effectiveness varies from 0.82 for TAF/FTC + DRV/r (AR) to 0.91 for TAF/FTC+DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC + RAL (PR), respectively. Conclusion: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR)


Introducción El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP), pautas alternativas (PA) y otras pautas (OP) para el tratamiento antirretroviral (TAR) como terapia de inicio en pacientes infectados por VIH para 2018. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con PP y PA. Métodos: Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral <50 copias/ml en la semana 48 en análisis por intención de tratar. Se definió coste de iniciar tratamiento con una pauta como los costes del TAR y de todas sus consecuencias (efectos adversos, cambios de pauta y estudio de resistencias) que se producen en las siguientes 48 semanas. Se utilizó la perspectiva del Sistema Nacional de Salud, considerando solo costes directos diferenciales: TAR (a precio oficial), manejo de efectos adversos, estudios de resistencias y determinación de HLA-B*5701. El ámbito es España, con costes de 2018. Se realizó un análisis de sensibilidad determinista construyendo 3 escenarios para cada pauta: basal, más favorable y más desfavorable. Resultados: En el escenario basal, los costes de iniciar tratamiento oscilaron entre 6.788 para TAF/FTC/RPV (PA) y 10.649 para TAF/FTC+RAL (PP). La eficacia osciló entre 0,82 para TAF/FTC+DRV/r (PA) y 0,91 para TAF/FTC+DTG (PP). La eficiencia, en términos de coste/eficacia, osciló entre 7.814 y 12.412 por respondedor a las 48 semanas, para ABC/3TC/DTG (PP) y TAF/FTC+RAL (PP), respectivamente. Conclusión: Considerando el precio oficial del TAR, la pauta más eficiente fue ABC/3TC/DTG (PP), seguida de TAF/FTC/RPV (PA) y AF/FTC/EVG/COBI (PA)


Assuntos
Humanos , Adulto , Antirretrovirais/economia , Antirretrovirais/uso terapêutico , Análise Custo-Benefício , HIV , Fármacos Anti-HIV/uso terapêutico
7.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30389268

RESUMO

BACKGROUND: The life expectancy of HIV-infected individuals has dramatically improved with potent antiretroviral therapies. However, organ-specific toxicities of some antiretrovirals and persistent inflammation and immune activation due to residual virus replication account for a high burden of age-associated comorbidities in the HIV population. METHODS: The prevalence of overt cardiovascular, renal and bone diseases as well as their major risk factors were cross-sectionally examined during the year 2014 in the VACH cohort, a large nationwide population of HIV-infected individuals in Spain. RESULTS: A total of 10,897 HIV-infected patients were examined. Seventy-one point four percent were male and the mean age was 48 years. Mean time since HIV diagnosis was 15.8 years and mean time on antiretroviral therapy was 13.1 years. The proportion of patients with undetectable viral load was 87.1%, whereas 65.7% had CD4 counts>500 cells/mm3. Overall, cardiovascular, renal and bone disease were recorded in 4.7%, 5.9% and 2.8%, respectively. The prevalence of major risk factors was as follows: smoking 51.3%, alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidaemia 72.6%, hypertension 25.6%, and osteoporosis 11.1%. In the subset of patients older than 55 years-old (18%), all figures for overt disease and their major risk factors were significantly greater. CONCLUSION: Major age-related medical conditions and most of their risk factors are highly prevalent in HIV-infected individuals on long-term antiretroviral therapy in Spain. Preventive actions, including careful selection of antiretroviral agents, should be prioritized in the ageing HIV population.

8.
J Hosp Infect ; 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30448277

RESUMO

BACKGROUND: Staphylococcus aureus meningitis is an uncommon nosocomial infection usually associated with neurosurgical procedures but spontaneous infections may occasionally appear. AIMS: To compare the features of meningitis caused by methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus and examine the prognostic factors for mortality, including MRSA infection and combined antimicrobial therapy. METHODS: Retrospective cohort study of 350 adults with S. aureus meningitis admitted to 11 hospitals in Spain (1981-2015). Logistic regression and propensity score matching were used to analyze prognostic factors. RESULTS: There were 118 patients (34%) with MRSA and 232 (66%) with MSSA. Postoperative infection (91% vs. 73%) and nosocomial acquisition (93% vs. 74%) were significantly more frequent in MRSA than in MSSA meningitis (P<0.001). Combined therapy was given to 118 (34%) patients. Overall 30-day mortality rate was 23%. On multivariate analysis, mortality was associated with severe sepsis or shock (odds ratio [OR], 9.9 [95% CI, 4.5-22.0], P<0.001), spontaneous meningitis (OR, 4.2 [95% CI, 1.9-9.1], P<0.001), McCabe-Jackson score rapidly or ultimately fatal (OR, 2.8 [95% CI, 1.4-5.4], P=0.002), MRSA infection (OR, 2.6 [95% CI, 1.3-5.3], P=0.006), and coma (OR, 2.6 [95% CI, 1.1-6.1], P<0.029). In postoperative cases, mortality was related to retention of cerebrospinal devices (OR, 7.9 [95% CI, 3.1-20.3], P<0.001). CONCLUSIONS: Clinical and epidemiological differences between MRSA and MSSA meningitis may be explained by the different pathogenesis of postoperative and spontaneous infection. In addition to the severity of meningitis and underlying diseases, MRSA infection was associated with increased mortality. Combined antimicrobial therapy was not associated with increased survival.

9.
BMJ Case Rep ; 20182018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30337283

RESUMO

A 69-year-old woman suffering from exophthalmos and facial pain came to us referred for aetiological diagnosis of exophthalmos. Orbital MRI showed thinned extrinsic ocular musculature, intraconal fat infiltration, retro-ocular compression and thickening of maxillary and sphenoid sinus walls. She had been suffering from diabetes insipidus for the last 7 years. During our diagnosis process, she presented signs of cardiac tamponade. Transthoracic heart ultrasound revealed large pericardial effusion and a heterogeneous mass that compressed the right ventricle. No osteosclerotic lesions on appendicular bones were present. Pericardiocentesis temporarily controlled tamponade and corticoid therapy temporarily abated exophthalmos. Pericardiectomy definitively resolved tamponade. Histological examination of pericardial tissue was conclusive of Erdheim-Chester disease. Exophthalmos responded to pegylated interferon-alpha-2a. Facial bone pain disappeared after zoledronic acid and interferon treatment. During interferon therapy, the patient suffered from a severe generalised desquamative exanthema that slowly resolved after discontinuing interferon. Diabetes insipidus remains controlled with desmopressin.

10.
J Acquir Immune Defic Syndr ; 79(4): 481-490, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30365452

RESUMO

BACKGROUND: The NEAT001/ANRS143 trial demonstrated noninferiority of ritonavir-boosted darunavir combined with either raltegravir (RAL + DRV/r) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC + DRV/r) in HIV-positive, antiretroviral-naive adults. In post hoc analyses, however, RAL + DRV/r showed inferiority in patients with baseline CD4 <200/mm and HIV-1 RNA ≥100,000 copies per milliliter. This preplanned ancillary study was conducted to assess whether differences in adherence might explain efficacy results. SETTING: Phase III, open-label, randomized, multicenter study in 15 European countries (ClinicalTrials.gov, NCT01066962). METHODS: Seven hundred seventy-four participants self-reported adherence (modified AIDS Clinical Trials Group questionnaire) over 96 weeks [383 RAL + DRV/r (twice daily; 5 pills/day), 391 TDF/FTC + DRV/r (once daily; 4 pills/day)]. Primary endpoint was ≥95% versus <95% adherence to prescribed doses recorded (1) over the last 4 days or (2) on the visual analogue scale over the last 30 days. RESULTS: Characteristics, except age, were similar between arms; 9% had CD4 <200 cells/mm and HIV-1 RNA ≥100,000 copies per milliliter. Adherence ≥95% in the last 4 days (P = 0.029) or at the visual analogue scale (P = 0.0072) was higher with TDF/FTC + DRV/r than with RAL + DRV/r. Adherence ≥95% over the last 4 days was associated with lower probability of virological failure (P = 0.015). Adherence in patients with baseline CD4 <200 cells/mm and HIV-1 RNA ≥100,000 copies per milliliter was similar to the rest of the population, and not significantly associated with efficacy measures, with no significant differences between arms. CONCLUSION: Adherence was high and slightly better in the TDF/FTC + DRV/r than in the RAL + DRV/r arm. No convincing evidence was found that higher failure rate in the RAL + DRV/r arm in the subgroup with worse baseline viroimmunological status is caused by adherence differences.

11.
AIDS ; 32(18): 2807-2819, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30289816

RESUMO

OBJECTIVES: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use (IDU) and heterosexual transmission. DESIGN: A multinational cohort study. METHODS: Within the EuroSIDA study, we assessed region-specific percentages of ART-coverage among those in care and virological suppression (<500 copies/ml) among those on ART, and analysed differences between transmission categories using logistic regression. RESULTS: Among 12 872 participants followed from 1 July 2014 to 30 June 2016, the percentages of ART-coverage and virological suppression varied between transmission categories, depending on geographical region (global P for interaction: P = 0.0148 for ART-coverage, P = 0.0006 for virological suppression). In Western [adjusted odds ratio (aOR) 1.41 (95% confidence interval 1.14-1.75)] and Northern Europe [aOR 1.68 (95% confidence interval 1.25-2.26)], heterosexuals were more likely to receive ART than MSM, while in Eastern Europe, there was some evidence that infection through IDU [aOR 0.60 (95% confidence interval 0.31-1.14)] or heterosexual contact [aOR 0.58 (95% confidence interval 0.30-1.10)] was associated with lower odds of receiving ART. In terms of virological suppression, people infected through IDU or heterosexual contact in East Central and Eastern Europe were around half as likely as MSM to have a suppressed viral load on ART, while we observed no differences in virological suppression across transmission categories in Western and Northern Europe. CONCLUSION: In our cohort, patterns of ART-coverage and virological suppression among key populations varied by geographical region, emphasizing the importance of tailoring HIV programmes to the local epidemic.

12.
AIDS Rev ; 20(3): 141-149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30264826

RESUMO

The advent of protease inhibitors (PI) in the mid-nineties and its use as part of triple combinations revolutionized the management of HIV infection. Since then, progression to AIDS and AIDS-related deaths can be prevented. However, antiretroviral therapy based on PI has been discouraged for a while given its lower tolerability compared to alternative options; and only recent improvements in pharmacotherapy have renewed the interest for the newest agents within this class. First, the tolerability of the latest PI darunavir (DRV) and atazanavir is much better than for older PI, such as indinavir or lopinavir. Second, metabolic abnormalities and/or drug interactions associated to ritonavir boosting have been ameliorated using cobicistat. Third, adding safer accompanying nucleos(t)ides, such as tenofovir alafenamide (TAF), have minimized further toxicity concerns of PI. Finally, the unique barrier to resistance and new single-tablet regimen (STR) presentation makes DRV, especially attractive for long-term therapy. The recent coformulation of DRV, cobicistat, TAF, and emtricitabine (DRV/c/TAF/FTC) within a single pill to be given once daily (Symtuza®) has positioned PI again at the frontline of HIV therapeutics. In this review, we discuss the results of studies that have assessed the efficacy and safety of the newest STR. In view of the current data, it seems worthy expanding the consideration of Symtuza® for a wider range of clinical scenarios, beyond the treatment of antiretroviral failures including first-line therapy and switching of otherwise virologically suppressed patients. The good tolerability and robust resistance profile should reward Symtuza® and position it among the preferred contemporary STRs.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30153121

RESUMO

BACKGROUND: The NEAT 001/ANRS 143 trial demonstrated non-inferiority of darunavir-ritonavir combined with either raltegravir (RAL+DRV/r) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC+DRV/r) in HIV-positive, antiretroviral-naive adults. In post-hoc analyses however, RAL+DRV/r showed inferiority in patients with baseline CD4+ <200/mm and HIV-1 RNA ≥100,000 copies/mL. This pre-planned ancillary study was conducted to assess whether differences in adherence might explain efficacy results SETTING:: Phase III, open-label, randomized, multicentre study in 15 European countries (ClinicalTrials.gov, NCT01066962). METHODS: 774 participants self-reported adherence (modified ACTG questionnaire) over 96 weeks (383 RAL+DRV/r [BID; 5 pills/daily], 391 TDF/FTC+DRV/r [QD; 4 pills/daily]. Primary endpoint was >95% versus <95% adherence to prescribed doses recorded a) over the last 4 days, or b) on the visual analogue scale (VAS) over the last 30 days RESULTS:: Characteristics, except age, were similar between arms; 9% had CD4+ <200 cells/mm and HIV-1 RNA ≥100,000 copies/mL. Adherence >95% in the last 4 days (p=0.029) or at VAS (p=0.0072) was higher with TDF/FTC+DRV/r than with RAL+DRV/r. Adherence >95% over the last 4 days was associated with lower probability of virological failure (p=0.015). Adherence in patients with baseline CD4+ <200 cells/mm and HIV-1 RNA ≥100,000 copies/mL was similar to the rest of the population, and not significantly associated with efficacy measures, with no significant differences between arms. Adherence was not different between baseline CD4 and HIV-1 RNA subgroups, overall and across arms (adherence ≥95% over the last 4 days: 90% for RAL+DRV/r versus 93% for TDF/FTC+DRV/r, p=0.91 for interaction of baseline strata with arm; adherence ≥95% on VAS: 89% versus 91%, respectively, p=0.86 for interaction of baseline strata with arm) CONCLUSION:: Adherence was high and slightly better in the TDF/FTC+DRV/r than in the RAL+DRV/r arm. Adherence differences did not explain inferiority of RAL+DRV/r in patients with CD4 <200/mm3 and HIV-1 RNA >100.000 copies/mL. No convincing evidence was found that higher failure rate in the RAL+DRV/r arm in the subgroup with worse baseline viro-immunological status is caused by adherence differencesThis is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

14.
Aging Cell ; 17(5): e12822, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30043445

RESUMO

Fibroblast growth factor 21 (FGF21) has been proposed to be an antiaging hormone on the basis of experimental studies in rodent models. However, circulating FGF21 levels are increased with aging in rodents and humans. Moreover, despite the metabolic health-promoting effects of FGF21, the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to FGF21. Here, we investigated serum FGF21 levels and expression of genes encoding components of the FGF21-response molecular machinery in adipose tissue from healthy elderly individuals (≥70 years old) and young controls. Serum FGF21 levels were increased in elderly individuals and were positively correlated with insulinemia and HOMA-IR, indices of mildly deteriorated glucose homeostasis. Levels of ß-Klotho, the coreceptor required for cellular responsiveness to FGF21, were increased in subcutaneous adipose tissue from elderly individuals relative to those from young controls, whereas FGF receptor-1 levels were unaltered. Moreover, total ERK1/2 protein levels were decreased in elderly individuals in association with an increase in the ERK1/2 phosphorylation ratio relative to young controls. Adipose explants from aged and young mice respond similarly to FGF21 "ex vivo". Thus, in contrast to what is observed in obesity and diabetes, high levels of FGF21 in healthy aging are not associated with repressed FGF21-responsiveness machinery in adipose tissue. The lack of evidence for impaired FGF21 responsiveness in adipose tissue establishes a distinction between alterations in the FGF21 endocrine system in aging and chronic metabolic pathologies.

15.
AIDS ; 32(14): 1995-2004, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-29912062

RESUMO

BACKGROUND AND AIMS: To investigate the uptake of hepatitis C virus (HCV) therapy among HIV/HCV-coinfected patients in the pan-European EuroSIDA study between 2011 and 2016. METHODS: All HCV-RNA+ patients were included. Baseline was defined as latest of anti-HCV+, January 2011 or enrolment in EuroSIDA. The incidence of starting first interferon-free direct-acting antiviral (DAA) therapy was calculated. Factors associated with starting interferon-free DAA were determined by Poisson regression. RESULTS: Among 4308 HCV-RNA+ patients (1255, 970, 663, 633, 787 from South, West, North, Central East and East Europe, respectively) with 11 863 person-years of follow-up, 1113 (25.8%) started any HCV therapy. Among patients with at least F3 fibrosis, more than 50% in all regions remained untreated. The incidence (per 1000 person-years of follow-up, 95% confidence interval) of starting DAA increased from 7.8 (5.9-9.8) in 2014 to 135.2 (122.0-148.5) in 2015 and 128.9 (113.5-144.3) in 2016. The increase was highest in North and West and intermediate in South, but remained modest in Central East and Eastern Europe. After adjustment, women, individuals from Central East or East, genotype 3, antiretroviral therapy naïve and those with detectable HIV-RNA were less likely to start DAA. Older persons, those with HCV-RNA more than 500 000 IU/ml and those with more advanced liver fibrosis were more likely to start DAA. CONCLUSION: Uptake of DAA therapy among HIV/HCV-coinfected patients increased considerably in Western Europe between 2014 and 2016, but was modest in Central East and East. In all regions more than 50% with at least F3 fibrosis remained untreated. Women were less likely to start DAA.

16.
Clin Infect Dis ; 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29912307

RESUMO

Background: Both immediate or deferred switching from a PI/r to DTG may improve lipid profile. Methods: NEAT022 is a European, open label, randomized, trial. HIV-infected adults ≥ 50 years or with a Framingham score ≥10% were eligible if HIV RNA < 50 copies/mL. Patients were randomized to switch the PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D) . Week 96 end-points were: proportion of patients with HIV RNA < 50 copies/ml, percentage change of lipid fractions and adverse events. Results: 415 patients were randomized: 205 to DTG-I and 210 to continue PI/r plus a deferred switch (DTG-D) at week 48 . The primary objective of non-inferiority at week 48 was met. At week 96, treatment success rate was 92.2 % in DTG-I arm and 87% in DTG-D arm (difference 5.2%, 95% CI -0.6 to 11). There were 5 virological failures in the DTG-I arm and 5 (1 while on PI/r and 4 after switching to DTG) in the DTG-D arm without selection of resistance mutations. There was no significant difference in terms of grade 3 or 4 AE´s or treatment modifying AE´s. Total cholesterol and other lipid fractions (except HDL) significantly (p<0.001) improved both after immediate and deferred switching to DTG overall and regardless of baseline PI/r strata. Conclusions: Both immediate and deferred switching from a PI/r to a DTG regimen in virologically suppressed HIV patients ≥ 50 years old or with a Framingham score ≥10% was highly efficacious, well tolerated and improved lipid profile.

17.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29884455

RESUMO

BACKGROUND: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. METHODS: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. RESULTS: In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC+RAL (PR). The effectiveness varies from 0.82 for TAF/FTC+DRV/r (AR) to 0.91 for TAF/FTC+DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC+RAL (PR), respectively. CONCLUSION: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR).

18.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 36(5): 268-276, mayo 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-176567

RESUMO

Introduction: GESIDA and the Spanish National AIDS Plan panel of experts have recommended preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral therapy (ART) as initial therapy in HIV-infected patients for 2017. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Methods: Economic assessment of costs and efficiency (cost-efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, resistance studies and HLA B*5701 screening. The setting was Spain and the costs correspond to those of 2017. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. Results: In the base case scenario, the cost of initiating treatment ranged from 6882 euro for TFV/FTC/RPV (AR) to 10,904 euros for TFV/FTC + RAL (PR). The efficacy varied from 0.82 for TFV/FTC + DRV/p (AR) to 0.92 for TAF/FTC/EVG/COBI (PR). The efficiency, in terms of cost-efficacy, ranged from 7923 to 12,765 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TFV/FTC + RAL (PR), respectively. Conclusion: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TFV/FTC/RPV (AR) and TAF/FTC/EVG/COBI (PR)


Introducción: El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP), pautas alternativas (PA) y otras pautas (OP) para el tratamiento antirretroviral (TARV) como terapia de inicio en pacientes infectados por VIH para 2017. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con PP y PA. Métodos: Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral < 50 copias/mL en la semana 48 en análisis por intención de tratar. Se definió coste de iniciar tratamiento con una pauta como los costes del TARV y de todas sus consecuencias (efectos adversos, cambios de pauta y estudio de resistencias) que se producen en las siguientes 48 semanas. Se utilizó la perspectiva del Sistema Nacional de Salud, considerando solo costes directos diferenciales: TARV (a precio oficial), manejo de efectos adversos, estudios de resistencias y determinación de HLA B*5701. El ámbito es España, con costes de 2017. Se realizó un análisis de sensibilidad determinista construyendo 3 escenarios para cada pauta: basal, más favorable y más desfavorable. Resultados: En el escenario basal, los costes de iniciar tratamiento oscilaron entre 6.882 euros para TFV/FTC/RPV (PA) y 10.904 euros para TFV/FTC + RAL (PP). La eficacia osciló entre 0,82 para TFV/FTC + DRV/p (PA) y 0,92 para TAF/FTC/EVG/COBI (PP). La eficiencia, en términos de coste/eficacia, osciló entre 7.923 y 12.765 euros por respondedor a las 48 semanas, para ABC/3TC/DTG (PP) y TFV/FTC + RAL (PP), respectivamente. Conclusión: Considerando el precio oficial del TARV, la pauta más eficiente fue ABC/3TC/DTG (PP), seguida de TFV/FTC/RPV (PA) y TAF/FTC/EVG/COBI (PP)


Assuntos
Humanos , Adulto , Custos de Medicamentos/estatística & dados numéricos , Análise Custo-Benefício , Terapia Antirretroviral de Alta Atividade/economia , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/economia , Infecções por HIV/tratamento farmacológico , Espanha , Guias de Prática Clínica como Assunto , Medicina Baseada em Evidências
19.
Artigo em Inglês | IBECS | ID: ibc-176574

RESUMO

Osteoporosis has become an emerging comorbid condition in people living with HIV (PLWH). The increase in survival and the progressive aging of PLWH will make this complication more frequent in the near future. In addition to the traditional risk factors affecting the general population, factors directly or indirectly associated with HIV infection, including antiretroviral therapy, can increase the risk of osteoporosis. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of osteoporosis in PLWH. This document is intended for all professionals who work in clinical practice in the field of HIV infection


La osteoporosis se ha convertido en una situación comórbida emergente en las personas infectadas por VIH. El incremento de la supervivencia y el envejecimiento progresivo de las personas infectadas por VIH harán que esta complicación sea más frecuente en un futuro cercano. Además de los factores de riesgo tradicionales, los factores directa o indirectamente asociados a la infección por VIH, incluyendo el tratamiento antirretroviral, pueden incrementar el riesgo de presentar osteoporosis. El presente artículo constituye un resumen ejecutivo del documento que actualiza las recomendaciones previas sobre la prevención y el tratamiento de la osteoporosis en las personas infectadas por VIH. Este documento va dirigido a todos los profesionales que ejercen la práctica clínica en el campo de la infección por VIH


Assuntos
Humanos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Osteoporose/induzido quimicamente , Medição de Risco , Fármacos Anti-HIV/uso terapêutico
20.
Atherosclerosis ; 273: 28-36, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29677628

RESUMO

BACKGROUND AND AIMS: Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. METHODS: To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months. Univariate and multivariate analyses were performed to evaluate the predictive power of NMR spectroscopy. RESULTS: VLDL-metabolism (including VLDL lipid concentrations, sizes, and particle numbers), total triglycerides and lactate levels resulted in good classifiers of dyslipidemia (AUC 0.903). Total particles/HDL-P ratio was significantly higher in ART-associated dyslipidemia compared to ART-normolipidemia (p = 0.001). Large VLDL-Ps were positively associated with both LDL-triglycerides (ρ 0.682, p < 0.001) and lactate concentrations (ρ 0.416, p < 0.001), the last one a marker of mitochondrial low oxidative capacity. CONCLUSIONS: Our data suggest that circulating metabolites have better predictive values for HIV/ART-related dyslipidemia onset than do the biochemical markers associated with conventional lipid measurements. NMR identifies changes in VLDL-P, lactate and LDL-TG as potential clinical markers of baseline HIV-dyslipidemia predisposition. Differences in circulating metabolomics, especially differences in particle size, are indicators of important derangements of mitochondrial function that are linked to ART-related dyslipidemia.

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