IrsiCaixa Foundation

Badalona, Spain

IrsiCaixa Foundation

Badalona, Spain
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Bonjoch A.,University of Barcelona | Bayes B.,University of Barcelona | Riba J.,University of Barcelona | Puig J.,University of Barcelona | And 5 more authors.
Antiviral Research | Year: 2010

We performed a cross-sectional study to determine the best method for estimating the glomerular filtration rate (GFR) in HIV-infected subjects. Isotopic GFR was correlated with 24-h urine creatinine clearance, cystatin C levels, and 3 creatinine-based equations-the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-in 15 patients. Cystatin C showed the strongest correlation with isotopic GFR (r= -0.760, p= 0.001). When cystatin C was used as the reference variable for all 106 patients, CKD-EPI proved to be superior to the other equations (r= -0.671, p< 0.001). Time with HIV infection, unsuppressed viral load, low CD4 T-cell counts, and use of protease inhibitors are related to an increased risk of renal impairment, leading us to recommend early initiation of antiretroviral therapy accompanied by a regular renal study. © 2010 Elsevier B.V.


Bonjoch A.,Autonomous University of Barcelona | Echeverria P.,Autonomous University of Barcelona | Perez-Alvarez N.,Autonomous University of Barcelona | Perez-Alvarez N.,University of Barcelona | And 5 more authors.
Antiviral Research | Year: 2012

We assessed the progress of renal damage after discontinuation of tenofovir (TDF) in patients who started therapy with normal renal parameters. Normal local reference values were as follows: estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation (MDRD), ≥60mL/min/1.73m2; creatinine, ≤1.20mg/dL; serum phosphate: ≥2.69mg/dL; proteinuria: <30mg/dL, and glycosuria: <20mg/dL in nondiabetic patients. A logistic regression analysis was used to evaluate factors related to normalization of renal function.We included 183 patients; 85% were male, and median (IQR) age was 44 (40-50). years. Time on TDF was 39 (22-63). months. After 22 (13-49.5). months from TDF discontinuation, renal parameters returned to normal values in 59% of patients, improved (without reaching normal values) in 9.8%, and did not improve in 31%. Median time until normalization was 4 (2-15.75). months, and time to maximum improvement in patients whose values did not return to normal was 14 (8.75-27.75). months. Follow-up was <12. months in 30% of the patients who did not improve. The only factors significantly associated with normalization of renal parameters were nadir CD4 T-cell count (p= 0.034; OR = 1.002, per 1 cell of increase) and CD4 T-cell count at the end of therapy with TDF (p= 0.030; OR = 1.033, per 1 cell of increase). Reversibility of renal damage was prompt and complete in 59% of patients receiving TDF-containing regimens and was associated with a higher nadir and current CD4+ T-cell count, suggesting a role of preserved cellular immunity in renal recovery in this population. © 2012 Elsevier B.V.


PubMed | St Elisabeth Hospital, National and Kapodistrian University of Athens, Rega Institute for Medical Research, National Institute For Infectious Diseases Prof Dr Matei Bals and 23 more.
Type: Journal Article | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2016

Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001.Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0.The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones.Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.


Llibre J.M.,Foundation University | Llibre J.M.,Autonomous University of Barcelona | Clotet B.,IrsiCaixa Foundation
AIDS Reviews | Year: 2012

Once-daily single-tablet regimens represent the paramount simplification of antiretroviral treatment achieved so far. They include drugs with favorable pharmacokinetics that allow once-daily administration, that do not need dose adjustments, have no additional toxicities, and do not require dissimilar intake conditions. Co-formulated efavirenz/tenofovir disoproxil fumarate/emtricitabine has been a gold standard of initial therapy since its approval in 2006. Galenic research and industry patent agreements may allow availability of single-tablet regimens with HIV-1 nonnucleoside reverse transcriptase inhibitors (efavirenz or rilpivirine), integrase inhibitors (cobicistat-boosted elvitegravir or dolutegravir), and protease inhibitors (cobicistat-boosted darunavir), combined with either tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The introduction of the new phamacoenhancer cobicistat as a potential substitution for ritonavir and the investigational agent GS-7340, with one-tenth the tenofovir mass, is a breakthrough in antiretroviral drug development. Many HIV-1-infected patients who are treatment-naive or treatment-experienced with susceptible virus will potentially have more options to reduce pill burden and optimize dosage schedules with one pill once-daily regimens.


Bonjoch A.,Foundation University | Figueras M.,Polytechnic University of Catalonia | Estany C.,Foundation University | Perez-Alvarez N.,Foundation University | And 10 more authors.
AIDS | Year: 2010

Background: Low bone mineral density (BMD) is an emerging metabolic condition in HIV-infected patients; however, data on progression of this disease are scarce. Methods: We studied 671 patients with at least one dual-energy X-ray absorptiometry scan (391 of them ≥2 scans) to determine the prevalence and progression of BMD and establish related factors. Linear regression and logistic polytomic regression were used for the cross-sectional study and mixed effects and generalized estimating equations were used for the longitudinal study. Results: Osteopenia and osteoporosis were diagnosed in 47.5 and 23%, respectively. Progression to bone demineralization was observed in 28% of the patients over a median of 2.5 years (12.5% progressed to osteopenia and 15.6% to osteoporosis). In the 105 patients with at least 5 years of follow-up, progression was 47% (18% to osteopenia; 29% to osteoporosis). Factors associated with bone loss and progression were age [odds ratio (OR) 1.07; 95% confidence interval (CI) 1.05-1.08; P<0.0001], male sex (OR 2.23; 95% CI 1.77-2.8; P<0.0001), low body mass index (OR 1.14; 95% CI 1.11-1.17; P<0.0001), time on protease inhibitor (OR 1.18; 95% CI 1.12-1.24; P<0.0001), time on tenofovir (OR 1.08; 95% CI 1.03-1.14; P<0.0019), and current use of protease inhibitors (OR 1.64; 95% CI 1.35-2.04; P<0.0001). Conclusions: Our results show a high prevalence of and considerable progression to osteopenia/ osteoporosis in our cohort. Our findings support the importance of applying adequate strategies to prevent bone demineralization and of close monitoring of BMD in HIV-infected patients, specifically in at-risk patients who are taking antiretrovirals that affect bone mineralization. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Izquierdo-Useros N.,IrsiCaixa Foundation | Naranjo-Gomez M.,Laboratory of Immunobiology for Research and Application to Diagnosis LIRAD | Naranjo-Gomez M.,Autonomous University of Barcelona | Erkizia I.,IrsiCaixa Foundation | And 7 more authors.
PLoS Pathogens | Year: 2010

Exosomes are secreted cellular vesicles that can induce specific CD4 + T cell responses in vivo when they interact with competent antigen-presenting cells like mature dendritic cells (mDCs). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic and exosome exchange pathway, moving between cells in the absence of fusion events in search of adequate target cells. Here, we discuss recent data supporting this hypothesis, which further explains how DCs can capture and internalize retroviruses like HIV-1 in the absence of fusion events, leading to the productive infection of interacting CD4+ T cells and contributing to viral spread through a mechanism known as trans-infection. We suggest that HIV-1 can exploit an exosome antigen-dissemination pathway intrinsic to mDCs, allowing viral internalization and final trans-infection of CD4+ T cells. In contrast to previous reports that focus on the ability of immature DCs to capture HIV in the mucosa, this review emphasizes the outstanding role that mature DCs could have promoting trans-infection in the lymph node, underscoring a new potential viral dissemination pathway. © 2010 Izquierdo-Useros et al.


Luo R.,University of Delaware | Cardozo E.F.,University of Delaware | Piovoso M.J.,Pennsylvania State University | Wu H.,University of Rochester | And 5 more authors.
Journal of the Royal Society Interface | Year: 2013

A model of reservoir activation and viral replication is introduced accounting for the production of 2-LTR HIV-1 DNA circles following antiviral intensification with the HIV integrase inhibitor raltegravir, considering contributions of de novo infection events and exogenous sources of infected cells, including quiescent infected cell activation. The model shows that a monotonic increase in measured 2-LTR concentration post intensification is consistent with limited de novo infection primarily maintained by sources of infected cells unaffected by raltegravir, such as quiescent cell activation, while a transient increase in measured 2-LTR concentration is consistent with significant levels of efficient (R0 > 1) de novo infection. The model is validated against patient data from the INTEGRAL study and is shown to have a statistically significant fit relative to the null hypothesis of random measurement variation about a mean. We obtain estimates and confidence intervals for the model parameters, including 2-LTR half-life. Seven of the 13 patients with detectable 2-LTR concentrations from the INTEGRAL study have measured 2-LTR dynamics consistent with significant levels of efficient replication of the virus prior to treatment intensification. © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License.


Vandekerckhove L.P.R.,Ghent University | Wensing A.M.J.,University Utrecht | Kaiser R.,University of Cologne | Brun-Vezinet F.,Bichat Claude Bernard University Hospital | And 18 more authors.
The Lancet Infectious Diseases | Year: 2011

Viral tropism is the ability of viruses to enter and infect specific host cells and is based on the ability of viruses to bind to receptors on those cells. Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. In most European countries, HIV tropism is identified with tropism phenotype testing. New data support genotype analysis of the HIV third hypervariable loop (V3) for the identification of tropism. The European Consensus Group on clinical management of tropism testing was established to make recommendations to clinicians and clinical virologists. The panel recommends HIV-tropism testing for the following groups: drug-naive patients in whom toxic effects are anticipated or for whom few treatment options are available; patients who have poor tolerability to or toxic effects from current treatment or who have CNS pathology; and patients for whom therapy has failed and a change in treatment is considered. In general, an enhanced sensitivity Trofile assay and V3 population genotyping are the recommended methods. Genotypic methods are anticipated to be used more frequently in the clinical setting because of their greater accessibility, lower cost, and faster turnaround time than other methods. For the interpretation of V3 loop genotyping, clinically validated systems should be used when possible. Laboratories doing HIV tropism tests should have adequate quality assurance measures. Similarly, close collaboration between HIV clinicians and virologists is needed to ensure adequate diagnostic and treatment decisions. © 2011 Elsevier Ltd.


Bastos-Amador P.,Institute Investigacio Germans Trias i Pujol | Perez-Cabezas B.,Institute Investigacio Germans Trias i Pujol | Izquierdo-Useros N.,IrsiCaixa Foundation | Puertas M.C.,IrsiCaixa Foundation | And 5 more authors.
Journal of Leukocyte Biology | Year: 2012

cDCs and pDCs differ in multiple aspects. Among those, antigen capture is a recognized feature of cDCs, whereas pDCs display poor capacity to capture cell-derived antigens. However, animal models of organ transplantation suggested a role for pDCs in tolerance induction via phagocytosis of donor antigens. In a transplantation setting, microvesicles, such as apopto-tic bodies and exosomes secreted by the graft, may be potential sources of alloantigen. Here, we tested the capacity of human pDCs to capture exosomes and ap-optotic bodies from Jurkat T cells. Exosomes and apo-ptotic bodies were indeed captured by pDCs, although required longer times of incubation when compared with the highly endocytic cDCs. In cDCs and pDCs, exo-some capture was more efficient than apoptotic bodies. Endocytosis inhibitors clearly impaired exosome capture by cDCs, although this could not be verified in pDCs as a result of cellular toxicity. Functionally, capture of Jurkat-derived exosomes did not induce nor prevent pDC maturation, and exosome-loaded pDCs induced T cell proliferation, suggesting a link between capture and presentation. Thus, exosomes and apo-ptotic bodies may be sources of antigen for human pDCs. © Society for Leukocyte Biology.


Darwich L.,Lluita Contra la SIDA Foundation | Darwich L.,Autonomous University of Barcelona | Canadas M.-P.,Lluita Contra la SIDA Foundation | Videla S.,Lluita Contra la SIDA Foundation | And 9 more authors.
Sexually Transmitted Diseases | Year: 2013

BACKGROUND: We studied the type-specific infection of human papillomavirus (HPV) at the anal canal and penile site in a cohort of HIV-infected men. METHODS: Prevalence, clearance, and incidence of specific HPV types in the anal canal and penis were determined in 733 HIV-infected men from the Spanish CAn Ruti HIV+ Men ([CARH•MEN]) cohort (538 men who have sex with men [MSM] and 195 heterosexual men). RESULTS: In both groups, the most prevalent high-risk type was HPV-16 (anal canal [31.6% MSM; 6.8% heterosexual] and penis [4.8% MSM; 6.8% heterosexual]). The most prevalent low-risk type was HPV-6 (anal canal [23.2% MSM; 12.8% heterosexual], penis [8.1% MSM; 8.9% heterosexual]). Anal prevalence was significantly higher in MSM, as was incidence, except for HPV-16, which was similar between male groups (5.9 new cases per 1000 person-months [95% confidence interval, 4.3-7.9] in MSM; 4.4 [95% confidence interval, 2.5-7.2] in heterosexual men; P > 0.05). The anal clearance rate of the different HPV types and retention time of infection were similar in both groups, as well as the HPV infection of the penis. CONCLUSIONS: HIV-infected MSM had a high prevalence of HPV infection at the anal canal; however, heterosexual HIV-infected men were also at risk for acquiring and sustaining persistent high-risk HPV types at the anal and penile site and are at risk for developing dysplasia in the future. All HIV-infected men should be recommended for routinely anal HPV screening. Copyright © 2013 American Sexually Transmitted Diseases Association All rights reserved.

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