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1.
Liver Int ; 44(2): 603-613, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38100128

RESUMEN

OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.


Asunto(s)
Carcinoma Hepatocelular , Coinfección , Consumidores de Drogas , Infecciones por VIH , Hepatitis C , Hepatitis D , Neoplasias Hepáticas , Abuso de Sustancias por Vía Intravenosa , Masculino , Humanos , Femenino , Virus de la Hepatitis Delta/genética , Antígenos de Superficie de la Hepatitis B , Carcinoma Hepatocelular/epidemiología , Coinfección/epidemiología , Neoplasias Hepáticas/epidemiología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Hepatitis D/complicaciones , Hepatitis D/epidemiología , Anticuerpos Antihepatitis , Prevalencia , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , ARN , Hepatitis C/complicaciones , Virus de la Hepatitis B/genética
2.
AIDS Behav ; 28(8): 2746-2754, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38836986

RESUMEN

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity.


Asunto(s)
Infecciones por VIH , Humanos , Infecciones por VIH/prevención & control , Femenino , Masculino , Comunicación , Inteligencia Artificial , Prueba de VIH , Comunicación en Salud/métodos , Conocimientos, Actitudes y Práctica en Salud
3.
New Microbiol ; 46(4): 367-380, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38252048

RESUMEN

Definitive data on the long-term success of the latest antiretroviral therapy (ART) strategies are still lacking. A panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow ART over time. Panelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Ninety infectious diseases specialists from several Infectious Diseases Centers in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long-term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need for an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality-of-life monitoring during the standard follow up of people living with HIV. The consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.


Asunto(s)
Enfermedades Transmisibles , Infecciones por VIH , Humanos , Calidad de Vida , Antirretrovirales/uso terapéutico , Consenso , Infecciones por VIH/tratamiento farmacológico
4.
Microb Pathog ; 185: 106377, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37839760

RESUMEN

The prevalence of Blastocystis sp., its genetic diversity and the distribution of circulating subtypes (STs) were molecularly investigated in a cohort of autochthonous and immigrant patients with gastrointestinal symptoms hospitalized over the period February 2022-June 2023 at the Policlinico Ospedaliero-Universitario "Riuniti", Foggia, in Southern Italy. The population variables, including patient geographical origin, gender and age classes were reported. Out of the 927 investigated patients, 36 (3.9%) were positive for Blastocystis sp. A statistically significant association with African origin and age classes >18 years old was found. ST1 (allele 4), ST2 (alleles 9, 13), ST3 (alleles 34, 36) and ST4 (allele 92) were the subtypes detected with a different distribution between autochthonous and immigrant patients. Co-infections with enteric protozoa such as Giardia duodenalis and Dientamoeba fragilis, pathogenic bacteria as Clostridioides difficile, Campylobacter jejuni and Aeromonas sp. and viral infections such as Norovirus were found in 33% of cases. This is the first study of Blastocystis sp., its circulating subtypes and allele variability among patients with different geographical origin in an area of Southern Italy, in the Central Mediterranean, characterized by high immigrant pressure. These results provide baseline data to better investigate a potential interaction between Blastocystis sp. and other risk factors in patients with gastrointestinal symptoms.


Asunto(s)
Infecciones por Blastocystis , Blastocystis , Emigrantes e Inmigrantes , Humanos , Adolescente , Blastocystis/genética , Infecciones por Blastocystis/epidemiología , Infecciones por Blastocystis/parasitología , Prevalencia , Variación Genética , Italia/epidemiología , Heces/parasitología , Filogenia
5.
Liver Int ; 43(10): 2130-2141, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37649460

RESUMEN

BACKGROUND AND AIMS: Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown. METHODS: Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models. RESULTS: Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36-.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91-2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17-2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62-.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56-.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR .18, 95% CI: .07-.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022. CONCLUSIONS: The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort.


Asunto(s)
COVID-19 , Infecciones por VIH , Hepatitis C , Humanos , Niño , Antivirales/uso terapéutico , Estudios Prospectivos , Reinfección , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , ARN , Viremia , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología
6.
Pharmacol Res ; 196: 106898, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37648103

RESUMEN

BACKGROUND: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. METHODS: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. RESULTS: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. CONCLUSIONS: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

7.
Int J Mol Sci ; 24(13)2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37446170

RESUMEN

The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild (MD) and severe (SD) COVID-19 patients. Here we showed that of the 84 miRNAs analyzed, 8 were differently expressed in the plasma and saliva of SD patients. In particular: (1) miRNAs let-7a-5p, let-7b-5p, and let-7c-5p were significantly downregulated; and (2) miR-23a and b and miR-29c, as well as three immunomodulatory miRNAs (miR-34a-5p, miR-181d-5p, and miR-146) were significantly upregulated. The production of pro-inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-8, IL-9, and TNFα) and chemokines (CCL2 and RANTES) increased in both the saliva and plasma of SD and MD patients. Notably, disease severity correlated with NA and immune activation. Monitoring these parameters could help predict disease outcomes and identify new markers of disease progression.


Asunto(s)
COVID-19 , MicroARNs , Humanos , COVID-19/genética , SARS-CoV-2/genética , MicroARNs/genética , Citocinas
8.
AIDS Care ; 33(12): 1621-1626, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33242983

RESUMEN

The loss of patients to follow up is a major issue related to HIV management. Our research was aimed to evaluate, in a single Italian centre, the rate of patients lost to follow-up (LFU) over 10 years, to describe their socio-demographic and clinical features, and to identify predictors of disengagement from care. Between 2008 and 2017, 563 subjects were LFU. Over the years, the proportion of LFU on the number of patients followed per year, decreased from 6.5% in 2008 to 4.8% in 2017 (p for trend = 0.255). Four different subgroups were identified among LFU:116 patients resulted untraceable; 192 had died; 144 were re-engaged elsewhere; 111 were subsequently re-engaged in our centre. Old age (OR 1.08, 95%, CI = 1.06-1.11; p < 0.001), AIDS (OR = 1.66, 95% CI = 1.04-2.64; p = 0.031), drug addiction (OR = 1.91, 95% CI = 1.07-3.41; p = 0.027) were predictors of death at multivariable analysis. Main predictors of being untraceable were non-Italian nationality (OR = 4.23, 95% CI = 2.19-8.16; p < 0.001) and a short history of cART (OR = 0.93, 95% CI = 0.88-0.99; p = 0.026). Subjects living far from our Centre were often re-engaged elsewhere (OR = 2.36, 95% CI = 1.34-4.15; p = 0.002). According to our analysis, the problem LFU is still relevant: strategies to empower retention in care are thus necessary.


Asunto(s)
Infecciones por VIH , Etnicidad , Infecciones por VIH/tratamiento farmacológico , Humanos , Perdida de Seguimiento
9.
Acta Haematol ; 144(5): 580-584, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33878755

RESUMEN

Recently, a significant cluster of pneumonia caused by a novel betacoronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) was described initially in China and then spread throughout the world. Like other coronaviridae, the viral transmission occurs mainly through droplets. In addition, the virus has been detected in different clinical specimens, suggesting a potential transmission by other routes, including blood transfusion. However, the potential risk of transmission of SARS-CoV-2 via blood products is still unclear. The aim of our study was to investigate the prevalence of antibodies against SARS-CoV-2 among blood donors from South-Eastern Italy. Moreover, in the seropositive donors, we searched for the presence of the virus in nasopharyngeal swabs and in plasma samples. Overall, 1,797 blood donors from the Apulia region were tested for anti-SARS-CoV-2 antibodies, using a commercially available assay. Only 18/1,797 donors (1.0%) tested positive for anti-SARS-CoV-2 antibodies; in none of them SARS-CoV-2 viral RNA was detected in nasopharyngeal swabs and in plasma samples. Our results indicate that most of the blood donors in Apulia remained uninfected during this wave of the pandemic; further, none had detectable virus both in nasopharyngeal swabs and in blood samples. The risk to carry and transmit the virus by healthy and asymptomatic blood donors is probably very low.


Asunto(s)
Anticuerpos Antivirales/sangre , Donantes de Sangre , COVID-19/patología , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , COVID-19/virología , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Nasofaringe/virología , ARN Viral/análisis , ARN Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Carga Viral , Adulto Joven
10.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34638539

RESUMEN

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient's outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.


Asunto(s)
COVID-19/sangre , Esfingolípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , Femenino , Humanos , Lipidómica , Masculino , Persona de Mediana Edad , Pronóstico , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Esfingolípidos/análisis , Esfingomielinas/análisis , Esfingomielinas/sangre , Adulto Joven
11.
J Antimicrob Chemother ; 74(5): 1363-1367, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30698801

RESUMEN

OBJECTIVES: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals. METHODS: The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression. RESULTS: Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05). CONCLUSIONS: In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , Adulto , Recuento de Linfocito CD4/estadística & datos numéricos , Cobicistat/efectos adversos , Cobicistat/uso terapéutico , Estudios de Cohortes , Femenino , Inhibidores de Integrasa VIH/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Italia , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Quinolonas/efectos adversos , Quinolonas/uso terapéutico , Raltegravir Potásico/efectos adversos , Raltegravir Potásico/uso terapéutico , Análisis de Regresión , Análisis de Supervivencia , Insuficiencia del Tratamiento
12.
Malar J ; 16(1): 149, 2017 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-28410610

RESUMEN

BACKGROUND: Imported cases of multidrug resistant Plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in Western countries and their management is often challenging. This is also due to an inadequate knowledge and implementation of health prevention measures. CASE REPORT: A complex case of imported malaria caused by Plasmodium vivax/P. falciparum isolates in a patient who was not taking chemoprophylaxis while he was travelling in Cambodia is reported in this article. After failures of artemisinin-based and both oral and intravenous quinine-based regimens, a multidrug resistant P. falciparum was detected. The patient was successfully treated with atovaquone-proguanil. CONCLUSIONS: This experience highlights the importance of a careful management that should be based not only on the most up-to-date guidelines, but also on the awareness of a rapidly evolving scenario.


Asunto(s)
Resistencia a Múltiples Medicamentos , Malaria/parasitología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/aislamiento & purificación , Plasmodium vivax/efectos de los fármacos , Plasmodium vivax/aislamiento & purificación , Viaje , Adulto , Artemisininas/farmacología , Artemisininas/uso terapéutico , Atovacuona/uso terapéutico , Cambodia , Coinfección/diagnóstico , Coinfección/parasitología , Combinación de Medicamentos , Humanos , Lactonas/farmacología , Lactonas/uso terapéutico , Malaria/diagnóstico , Masculino , Proguanil/uso terapéutico , Quinina/farmacología , Quinina/uso terapéutico , Resultado del Tratamiento
13.
PLoS Genet ; 10(3): e1004189, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24675550

RESUMEN

The antigenic repertoire presented by MHC molecules is generated by the antigen processing and presentation (APP) pathway. We analyzed the evolutionary history of 45 genes involved in APP at the inter- and intra-species level. Results showed that 11 genes evolved adaptively in mammals. Several positively selected sites involve positions of fundamental importance to the protein function (e.g. the TAP1 peptide-binding domains, the sugar binding interface of langerin, and the CD1D trafficking signal region). In CYBB, all selected sites cluster in two loops protruding into the endosomal lumen; analysis of missense mutations responsible for chronic granulomatous disease (CGD) showed the action of different selective forces on the very same gene region, as most CGD substitutions involve aminoacid positions that are conserved in all mammals. As for ERAP2, different computational methods indicated that positive selection has driven the recurrent appearance of protein-destabilizing variants during mammalian evolution. Application of a population-genetics phylogenetics approach showed that purifying selection represented a major force acting on some APP components (e.g. immunoproteasome subunits and chaperones) and allowed identification of positive selection events in the human lineage. We also investigated the evolutionary history of APP genes in human populations by developing a new approach that uses several different tests to identify the selection target, and that integrates low-coverage whole-genome sequencing data with Sanger sequencing. This analysis revealed that 9 APP genes underwent local adaptation in human populations. Most positive selection targets are located within noncoding regions with regulatory function in myeloid cells or act as expression quantitative trait loci. Conversely, balancing selection targeted nonsynonymous variants in TAP1 and CD207 (langerin). Finally, we suggest that selected variants in PSMB10 and CD207 contribute to human phenotypes. Thus, we used evolutionary information to generate experimentally-testable hypotheses and to provide a list of sites to prioritize in follow-up analyses.


Asunto(s)
Presentación de Antígeno/genética , Selección Genética , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/inmunología , Alelos , Animales , Presentación de Antígeno/inmunología , Antígenos CD/genética , Antígenos CD/inmunología , Evolución Molecular , Genética de Población , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Mamíferos , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/inmunología , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , NADPH Oxidasa 2 , NADPH Oxidasas/genética , NADPH Oxidasas/inmunología , Filogenia
14.
New Microbiol ; 39(4): 290-294, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27551725

RESUMEN

In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm. Virological failure was detected in only one patient receiving LPV/r-MT. The LPV/r-MT arm showed a modest worsening in lipid profile.


Asunto(s)
Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Darunavir/administración & dosificación , Femenino , Humanos , Lopinavir/administración & dosificación , Masculino , Persona de Mediana Edad , Ritonavir/administración & dosificación
15.
J Infect Dis ; 211(2): 178-86, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25081936

RESUMEN

BACKGROUND: Chronic cytomegalovirus (CMV) infection has been associated with immunosenescence and immunoactivation in the general population. In human immunodeficiency virus type 1 (HIV-1)-infected people, CMV coinfection, in addition to residual HIV replication and microbial translocation, has been proposed as a key factor in sustaining immune activation, even in individuals with a controlled HIV load. METHODS: Patients from the ICONA Study with at least 1 CMV immunoglobulin G (IgG) test available without active CMV disease were included in the analysis. AIDS-defining event or AIDS-related death and severe non-AIDS-defining event or non-AIDS-related death were taken as clinical progression end points. Independent predictors of CMV were identified by multivariable logistic regression. Probabilities of reaching the end points were estimated by survival analyses. RESULTS: A total of 6111 subjects were included, of whom 5119 (83.3%) were CMV IgG positive at baseline. Patients with CMV IgG positivity at baseline were more likely to develop a severe non-AIDS-defining event/non-AIDS-related death (adjusted hazard ratio [HR], 1.53 [95% confidence interval {CI}, 1.08-2.16]. In particular, CMV seropositivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 [95% CI, .97-5.32]). CONCLUSIONS: In our study population, CMV/HIV coinfection was associated with the risk of severe non-AIDS-defining events/non-AIDS-related death, especially with cardiovascular and cerebrovascular events, independently of other prognostic factors. This finding supports a potential independent role of CMV coinfection in vascular/degenerative organ disorders in HIV-infected subjects.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Enfermedades Cardiovasculares/epidemiología , Trastornos Cerebrovasculares/epidemiología , Infecciones por Citomegalovirus/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Adulto , Anticuerpos Antivirales/sangre , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Estudios Prospectivos , Medición de Riesgo
16.
Mol Biol Evol ; 31(9): 2402-14, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24930137

RESUMEN

The protein product of the myxovirus resistance 2 (MX2) gene restricts HIV-1 and simian retroviruses. We demonstrate that MX2 evolved adaptively in mammals with distinct sites representing selection targets in distinct branches; selection mainly involved residues in loop 4, previously shown to carry antiviral determinants. Modeling data indicated that positively selected sites form a continuous surface on loop 4, which folds into two antiparallel α-helices protruding from the stalk domain. A population genetics-phylogenetics approach indicated that the coding region of MX2 mainly evolved under negative selection in the human lineage. Nonetheless, population genetic analyses demonstrated that natural selection operated on MX2 during the recent history of human populations: distinct selective events drove the frequency increase of two haplotypes in the populations of Asian and European ancestry. The Asian haplotype carries a susceptibility allele for melanoma; the European haplotype is tagged by rs2074560, an intronic variant. Analyses performed on three independent European cohorts of HIV-1-exposed seronegative individuals with different geographic origin and distinct exposure route showed that the ancestral (G) allele of rs2074560 protects from HIV-1 infection with a recessive effect (combined P = 1.55 × 10(-4)). The same allele is associated with lower in vitro HIV-1 replication and increases MX2 expression levels in response to IFN-α. Data herein exploit evolutionary information to identify a novel host determinant of HIV-1 infection susceptibility.


Asunto(s)
Pueblo Asiatico/genética , Resistencia a la Enfermedad , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Proteínas de Resistencia a Mixovirus/genética , Población Blanca/genética , Biología Computacional/métodos , Evolución Molecular , Variación Genética , VIH-1/patogenicidad , Haplotipos , Humanos , Modelos Genéticos , Proteínas de Resistencia a Mixovirus/química , Filogenia , Selección Genética
17.
Retrovirology ; 12: 80, 2015 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-26399852

RESUMEN

BACKGROUND: The genetic bases of natural resistance to HIV-1 infection remain largely unknown. Recently, two genome-wide association studies suggested a role for variants within or in the vicinity of the CYP7B1 gene in modulating HIV susceptibility. CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses. We analyzed the frequency of two previously described CYP7B1 variants (rs6996198 and rs10808739) in three independent cohorts of HIV-1 infected subjects and HIV-1 exposed seronegative individuals (HESN). FINDINGS: rs6996198 and rs10808739 were genotyped in three case/control cohorts of sexually-exposed HESN and HIV-1-infected individuals from Italy, Peru and Colombia. Comparison of the allele and genotype frequencies of the two SNPs under different models showed that the only significant difference was seen for rs6996198 in the Peruvian sample (nominal p = 0.048, dominant model). For this variant, a random-effect meta-analysis yielded non-significant results (dominant model, p = 0.78) and revealed substantial heterogeneity among cohorts. No significant effect of the rs10808739 allelic status on HIV-1 infection susceptibility (additive model, p = 0.30) emerged from the meta-analysis. CONCLUSIONS: Although our study had limited power to detect association due to the small sample size, comparisons among the three cohorts revealed very similar allelic and genotypic frequencies in HESN and HIV-1 positive subjects. Overall, these data indicate that the two GWAS-defined variants in the CYP7B1 region do not strongly influence HIV-1 infection susceptibility.


Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Inmunidad Innata/genética , Esteroide Hidroxilasas/genética , Adulto , Alelos , Familia 7 del Citocromo P450 , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Masculino , Polimorfismo de Nucleótido Simple
19.
J Immunol ; 188(2): 818-23, 2012 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-22174453

RESUMEN

TLR3 recognizes dsRNA and activates antiviral immune responses through the production of inflammatory cytokines and type I IFNs. Genetic association studies have provided evidence concerning the role of a polymorphism in TLR3 (rs3775291, Leu412Phe) in viral infection susceptibility. We genotyped rs3775291 in a population of Spanish HIV-1-exposed seronegative (HESN) individuals who remain HIV seronegative despite repeated exposure through i.v. injection drug use (IDU-HESN individuals) as witnessed by their hepatitis C virus seropositivity. The frequency of individuals carrying at least one 412Phe allele was significantly higher in IDU-HESN individuals compared with that of a matched control sample (odds ratio for a dominant model = 1.87; 95% confidence interval, 1.06-3.34; p = 0.023). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Similar results were obtained: the frequency of individuals carrying at least one 412Phe allele was significantly higher compared with that of a matched control sample (odds ratio, 1.79; 95% confidence interval, 1.05-3.08; p = 0.029). In vitro infection assays showed that in PBMCs carrying the 412Phe allele, HIV-1(Ba-L) replication was significantly reduced (p = 0.025) compared with that of Leu/Leu homozygous samples and was associated with a higher expression of factors suggestive of a state of immune activation (IL-6, CCL3, CD69). Similarly, stimulation of PBMCs with a TLR3 agonist indicated that the presence of the 412Phe allele results in a significantly increased expression of CD69 and higher production of proinflammatory cytokines including IL-6 and CCL3. The data of this study indicate that a common TLR3 allele confers immunologically mediated protection from HIV-1 and suggest the potential use of TLR3 triggering in HIV-1 immunotherapy.


Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Polimorfismo Genético/inmunología , Receptor Toll-Like 3/genética , Células Cultivadas , Estudios de Cohortes , Variación Genética/inmunología , Infecciones por VIH/prevención & control , Seronegatividad para VIH/genética , Seronegatividad para VIH/inmunología , Humanos , Italia , Leucina/genética , Masculino , Fenilalanina/genética , Estudios Prospectivos , España
20.
New Microbiol ; 37(2): 163-75, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24858643

RESUMEN

During these last two years less drug regimens (LDRs) in HIV, and in particular protease inhibitor (PI)/r-based strategies, have been explored both in clinical trials and in clinical practice. Many results are now available and more is known about how to use them safely and effectively. Understanding that an LDR strategy represents a real tailored therapeutic approach for the patient is crucial for the long-term success and positive management of HIV infection. Trust between patients and HIV specialists and a real focus on the patient's life are key factors for long life treatment success, in particular when using a LDR strategy. This is clearly shown by the HIV patient's journey (HPJ) methodology, used in an Italian national workshop to better define the criteria and challenges of LDR strategies. This paper shows the results of this complex process.


Asunto(s)
Quimioterapia/psicología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Inhibidores de la Proteasa del VIH/uso terapéutico , Toma de Decisiones , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/enzimología , Humanos
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