J M Gatell

University of Barcelona, Barcino, Catalonia, Spain

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Publications (419)2206.67 Total impact

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    ABSTRACT: Background: The proportion of HIV-controllers developing virologic, immunological or clinical progression and the baseline predictors of these outcomes have not been assessed in large cohorts. Methods: A multicenter cohort of HIV-controllers was followed from baseline [the first of the three HIV-1 RNA levels < 50 in elite (EC) or from 50-2000 copies/mL in viremic controllers (VC)] up to August 2011, to the development of a progression event [loss of viral load (VL) control, CD4 decline, AIDS or death) or to the censoring date (lost to follow-up or initiation of ART). Predictive models of progression at baseline and a risk score for the combined HIV-1 progression end point were calculated. Results: 475 HIV-1 controllers of whom 204 (42.9%) were EC with 2972 PYFU were identified. 141 (29.7%) patients lost VL control. CD4+ cell count declined in 229 (48.2%) patients.13 patients developed an AIDS event and 4 died. 287 (60.4%) developed a combined HIV-1 progression. Baseline predictors for the progression end points and for EC and VC patients were very similar: Risk for HIV-1 acquisition, baseline calendar year, CD4 nadir, VL load before baseline and hepatitis C virus coinfection. The probability of a combined HIV-1 progression at 5 years was 70% for EC with the highest score compared with 13% for those with the lowest. Conclusions: HIV-1 disease progression in EC and VC is frequent. We propose a baseline clinical score to easily classify these patients according to risk of progression. This score could be instrumental for taking clinical decisions and performing pathogenic studies.
    No preview · Article · Feb 2016 · AIDS
  • Josep M. Llibre · Sharon Walmsley · Josep M. Gatell
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    ABSTRACT: The advances seen in ART during the last 30 years have been outstanding. Treatment has evolved from the initial use of single agents as monotherapy. The ability to use HIV RNA as a surrogate marker for clinical outcomes allowed the more rapid evaluation of new therapies. This led to the understanding that triple-drug regimens, including a core agent (an NNRTI or a boosted PI) and two NRTIs, are optimal. These combinations have demonstrated continued improvements in their efficacy and toxicity as initial therapy. However, the need for pharmacokinetic boosting, with potential drug–drug interactions, or residual issues of efficacy or toxicity have persisted for some agents. Most recently, integrase strand transfer inhibitors, particularly dolutegravir, have shown unparalleled safety and efficacy and are currently the core agents of choice. Regimens that included only core agents or only backbone agents have not been as successful as combined therapy in antiretroviral-naive patients. It appears that at least one NRTI is needed for optimal performance and lamivudine and emtricitabine may be the ideal candidates. Several studies are ongoing of agents with longer dosing intervals, lower cost and new NRTI-saving strategies to address unmet needs.
    No preview · Article · Jan 2016 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Introduction: Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013. Materials and methods: We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models. Mortality results: 182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0-16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7-6.1/1000 py), external was lower [1.7/1000 py; (1.0-2.4/1000 py)]. Survival results: Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5-7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3-5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4-1.7) and heterosexual female (sHR:2.8; CI:1.1-7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7-123.2) and heterosexual male (sHR:11.8; CI:2.5-56.4) versus MSM. Conclusion and recommendation: There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.
    Full-text · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32–97), lowest in Northern Europe (median 44%, IQR 22–68%) and highest in Eastern Europe (median 99%, IQR 86–100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0–4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.
    Full-text · Article · Nov 2015 · PLoS ONE
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    ABSTRACT: Background: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. Guideline highlights: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. Conclusions: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.
    No preview · Article · Nov 2015 · HIV Medicine
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    ABSTRACT: The urgent need of effective therapies for MRSA infective endocarditis (IE) is cause of concern. We aimed to ascertain the in vitro and in vivo activity of the old antibiotic fosfomycin combined with different beta-lactams against methicillin-resistant (MRSA) and glycopeptide-intermediate resistant (GISA) S. aureus strains. Time-kill tests with ten isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC700788), the following intravenous regimens were compared: fosfomycin (2g q8h) plus imipenem (1g q6h) or ceftriaxone (2g q12h) (FOF+CRO), vancomycin at standard dose (VAN-SD) (1g q12h) and high-dose (VAN-HD) (1g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations was observed with FOF+IPM compared with VAN-SD (0 ([0-1]) vs. 2 [0-5.1] log CFU/g veg; P= 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] vs. 5/16 [31%]; P=0.02). GISA-ATCC700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO compared with VAN-SD (2 ([0-2]) and 0 ([0-2]) vs. 6.5 [2-6.9] logCFU/g veg; P<0.01). The number of sterilized vegetations after FOF+CRO was higher than VAN-SD or VAN-HD (8/15 [53%] vs. 4/20 [20%] or 4/20 [20%]; P=0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, showing that FOF+IPM significantly decreased PBP1 and PBP3 synthesis. These results allow clinicians considering the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.
    Full-text · Article · Nov 2015 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities. © 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    No preview · Article · Nov 2015
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    ABSTRACT: Objective To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy.Methods Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed.ResultsThirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm.Conclusions Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance.
    Full-text · Article · Sep 2015 · HIV Medicine
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    Full-text · Dataset · Aug 2015
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    Full-text · Dataset · Aug 2015
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    ABSTRACT: The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
    Full-text · Article · Aug 2015 · Enfermedades Infecciosas y Microbiología Clínica
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    ABSTRACT: Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p<0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes. © 2015 European Society of Clinical Microbiology and Infectious Diseases.
    Full-text · Article · Jul 2015 · Clinical Microbiology and Infection
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    ABSTRACT: HIV-1 specific immune responses induced by a dendritic cells (DCs) therapeutic vaccine might have some effect on viral reservoir. We measured total and integrated HIV-1 DNA in isolated CD4 T cells in patients on cART randomized to receive DC pulsed with autologous HIV-1 (n=24) (DC-HIV-1) or with non-pulsed DCs (n=12) (DC-control) at 6 time-points: before any cART, before STOP1 (first cART interruption 56 weeks before the first immunization to isolate virus for pulsing DCs), before and after vaccinations (VAC1 and VAC2) and at weeks 12 and 48 after second cART interruption. Vaccinations did not influence HIV-1 DNA levels in vaccinated subjects. After cART interruption post-vaccination (week 12), while total HIV-1 DNA significantly increased in both arms, integrated HIV-1 DNA did not change in vaccinees (1.8 to 1.9, p=0.22) and increased in controls (1.8 to 2.1, p=0.02) (p=0.03 for the difference between groups). However, this lack of increase of integrated HIV-1 DNA observed in DC-HIV-1 group was transient and at week 48 after cART interruption no differences were observed between groups. HIV-1 specific T cells responses at VAC2 time-point were inversely correlated with total and integrated HIV-1 after cART interruption in vaccinees (r=-0.69, p=0.002 and r=-0.82, p<0.0001, respectively). No correlations were found in controls. HIV-1-specific T-cell immune responses elicited by DC therapeutic vaccines drive changes in HIV-1 DNA after vaccination and cART interruption. There is an intense interest in developing strategies to target HIV-1 reservoirs that create barriers to cure. The development of therapeutic vaccines aimed at enhancing immune mediated clearance of virus producing cells is of high priority. Few therapeutic vaccine clinical trials have investigate the role of therapeutic vaccines as a strategy to safely eliminate or control viral reservoirs. We recently reported that a dendritic cell based therapeutic vaccine was able to decrease significantly viral set-point in vaccinated patients with a concomitant increase in HIV-1--specific T cell responses. HIV-1 specific T cell immune responses elicited by this therapeutic dendritic cell vaccine drove changes of viral reservoir after vaccinations and significantly delayed the replenishment of integrated HIV-1 DNA after cART interruption. These data help to understand how an immunization could shift the virus/host balance and are instrumental to better design strategies to reach the functional cure of HIV-1 infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Jun 2015 · Journal of Virology
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    ABSTRACT: Background: Although virus-specific responses are rarely detected by conventional approaches, we report here the detection of T-cell responses in HESN by two distinct assays. Methods: HIV-specific T cell responses were analyzed by ELISPOT in PBMC from HESN after a 48h-co-culture with boosted dendritic cells (bDC). Additionally, a boosted flow cytometry approach was used to capture anti-viral T cell responses. Host genetic factors and T cell activation were also analyzed to assess their implication on HIV exposure. Results: Of 45 HESN individuals tested, up to 11 (24,4%) showed at least one response to peptide pools covering HIV Gag and Nef. A positive correlation was observed between the intensity (p=0.0022) and magnitude (p=0.0174) of the response detected in the HESN and the viral load of the HIV+ partner. Moreover, the result from the boosted flow and cytomix analyses showed a dominant Th1- like response pattern against HIV antigens, especially in CD8 T cell population. Conclusions: The combined use of our bDC technique with a boosted flow cytometric approach allows us both to detect specific HIV positive responses in a higher percentage of HESN and to define specific effector function profiles. This study contributes to a better understanding of resistance to HIV infection.
    No preview · Article · May 2015 · AIDS
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    ABSTRACT: Ex vivo analysis of mitochondrial function may reveal HIV progression and the impact of ART. We propose a mitochondrial and apoptotic in vitro model using Jurkat T cells incubated with plasma. The objectives of this study were to evaluate mitochondrial and apoptotic lesions in this model in relation to HIV progression, and to assess the effect of >1 year of standard non-thymidine-containing therapy. This was a cross-sectional comparison among three age- and gender-matched groups (n = 19 × 3): healthy non-HIV-infected participants, HIV-infected long-term non-progressors (LTNPs) and standard antiretroviral-naive chronically infected patients [standard progressors (Sps)], longitudinally evaluated before (Sp1) and after (Sp2) >1 year of efavirenz + tenofovir + emtricitabine therapy. We analysed mitochondrial DNA content by RT-PCR, mitochondrial function by spectrophotometry, mitochondrial protein synthesis by western blot analysis, mitochondrial dynamics by western blot analysis (MFN2), apoptotic transition pore formation by western blot analysis (VDAC-1) and mitochondrial membrane potential and annexin V/propidium iodide fluorescence by flow cytometry. There was a decreasing non-significant trend towards lower mitochondrial parameters for HIV-infected values with respect to uninfected control reference values. HIV progression (LTNP versus Sp1) was associated with decreased mitochondrial genetic, functional and translational parameters, which partially recovered after treatment intervention (Sp2). Mitochondrial fusion showed a trend to decrease non-significantly in Sp patients compared with LTNP patients, especially after therapy. All apoptotic parameters showed a trend to increase in Sp1 with respect to LTNP, followed by recovery in Sp2. We proposed an in vitro model for mitochondrial and apoptotic assessment to test the effects of HIV infection and its therapy, resembling in vivo conditions. This model could be useful for clinical research purposes. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Full-text · Article · Apr 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Very little information is available on the involvement of newly-characterized adipokines in HIV/HAART-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multi-centre study that involved 558 HIV-1-infected patients treated with a stable HAART regimen, 240 of those with overt HALS and 318 without HALS. Epidemiological and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t-test, one-way ANOVA, χ(2) test, Pearson and Spearman correlations, and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p<0.001) and plasma omentin was significantly lower (p=0.001) in patients with HALS compared with those without HALS; differences in plasma levels of the remaining adipokines were non-significant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of AIDS. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/HAART and fat redistribution syndromes. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · Clinical Microbiology and Infection
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    Full-text · Dataset · Mar 2015
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    ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
    Full-text · Article · Mar 2015 · PLoS Medicine
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    ABSTRACT: A proportion of patients who spontaneously control viral load (controllers) experienced clinical progression. We hypothesized that microbial translocation would independently determine the rate of disease progression in controllers. sCD14, lipopolysaccharide-binding protein (LBP) and EndoCab levels were assessed in 114 antiretroviral-naive patients with CD4 T cells above 500 cells/μl (including 63 controllers and 51 noncontrollers). The independent predictive value of these markers on time to progression to the combined endpoint of AIDS, non-AIDS event, initiation of combination antiretroviral therapy (cART) or CD4 cell count less than 500 cells/μl was assessed using a Cox regression model. Most of the patients progressed to a combined endpoint (60%). Clinical progression in controllers was significantly lower than in noncontrollers (P = 0.02). Controllers with lower than the median baseline CD4 T-cell count and higher than the median baseline viral load, sCD14 and EndoCab levels had a worse prognosis (P < 0.0001, P = 0.007, P = 0.05 and P = 0.012), while noncontrollers with higher than the median baseline LBP level also had a worse prognosis (P = 0.019). sCD14 and LBP increased and EndoCab decreased over time [from baseline (median values: 1486, 17604 ng/ml and 68 MMU/ml, respectively, to the date of event or the last determination (median values: 1663, 20230 ng/ml and 49 MMU/ml), respectively] in controllers (P = 0.04, 0.08 and 0.0006, respectively). Microbial translocation seems to be an important determinant of clinical progression in HIV-infected controllers independently of viremia. Measures to improve the intestinal mucosa damage or decrease translocation could influence the outcome in these patients.
    Full-text · Article · Feb 2015 · AIDS
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    ABSTRACT: a Background: A proportion of patients who spontaneously control viral load (controllers) experienced clinical progression. We hypothesized that microbial translocation would independently determine the rate of disease progression in controllers. Methods: sCD14, lipopolysaccharide-binding protein (LBP) and EndoCab levels were assessed in 114 antiretroviral-naive patients with CD4 þ T cells above 500 cells/ml (including 63 controllers and 51 noncontrollers). The independent predictive value of these markers on time to progression to the combined endpoint of AIDS, non-AIDS event, initiation of combination antiretroviral therapy (cART) or CD4 þ cell count less than 500 cells/ml was assessed using a Cox regression model. Results: Most of the patients progressed to a combined endpoint (60%). Clinical progression in controllers was significantly lower than in noncontrollers (P ¼ 0.02). Controllers with lower than the median baseline CD4 þ T cell count and higher than the median baseline viral load, sCD14 and EndoCab levels had a worse prognosis (P < 0.0001, P ¼ 0.007, P ¼ 0.05 and P ¼ 0.012), while noncontrollers with higher than the median baseline LBP level also had a worse prognosis (P ¼ 0.019). sCD14 and LBP increased and EndoCab decreased over time [from baseline (median values: 1486, 17604 ng/ml and 68 MMU/ml, respectively, to the date of event or the last determination (median values: 1663, 20230 ng/ml and 49 MMU/ml), respectively] in controllers (P ¼ 0.04, 0.08 and 0.0006, respectively). Conclusion: Microbial translocation seems to be an important determinant of clinical progression in HIV-infected controllers independently of viremia. Measures to improve the intestinal mucosa damage or decrease translocation could influence the outcome in these patients.
    Full-text · Article · Feb 2015

Publication Stats

9k Citations
2,206.67 Total Impact Points

Institutions

  • 1982-2016
    • University of Barcelona
      • • Department of Medicine
      • • Facultad de Medicina
      Barcino, Catalonia, Spain
  • 2000-2015
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 1982-2015
    • Hospital Clínic de Barcelona
      • • Servicio de Enfermedades Infecciosas
      • • Servicio de Neumología
      Barcino, Catalonia, Spain
  • 2011-2013
    • TAISS - Técnicas Avanzadas de Investigación en Servicios de Salud
      Madrid, Madrid, Spain
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
    • Instituto de Salud Carlos III
      • National Center of Microbiology (CNM)
      Madrid, Madrid, Spain
  • 2007
    • Hospital Universitari Sant Joan de Reus
      Reus, Catalonia, Spain
    • Hospital Universitari Joan XXIII de Tarragona
      Tarraco, Catalonia, Spain
    • Granollers General Hospital
      Granollers, Catalonia, Spain
  • 2005
    • Deutsche Gesellschaft für Sportmedizin und Prävention e.V.
      Germany
  • 2004
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 2001
    • Hospital Clínico, Maracaibo
      Maracaibo, Zulia, Venezuela
  • 1999
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1998
    • Hospital Universitario Virgen del Rocío
      Hispalis, Andalusia, Spain
    • Hospital General Universitario Morales Meseguer
      Murcia, Murcia, Spain
  • 1994
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
    • Copenhagen University Hospital Hvidovre
      • Department of Infectious Diseases
      Hvidovre, Capital Region, Denmark