Montserrat Plana

Institut Marqués, Spain, Barcelona, Barcino, Catalonia, Spain

Are you Montserrat Plana?

Claim your profile

Publications (122)612.25 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Massive activation of infected CD4+ T cells during acute HIV-1 infection leads to reservoir seeding and T-cell destruction. During T-cell activation, the antiviral effect of the innate factor SAMHD1 is neutralized through phosphorylation at T592, allowing HIV-1 infection. Dasatinib, a tyrosine kinase inhibitor currently used for treating chronic myeloid leukemia, has been described to control HIV-1 replication through its negative effect on T-cell proliferation and viral entry. We demonstrate that Dasatinib can actually interfere with SAMHD1 phosphorylation in human peripheral blood lymphocytes, preserving its antiviral activity against HIV-1. Dasatinib prevented SAMHD1 phosphorylation in vitro and ex vivo, impairing HIV-1 retrotranscription and proviral integration. This was the major mechanism of action because the presence of Vpx, which degrades SAMHD1, in HIV-1 virions impeded the inhibitory effect of Dasatinib on HIV-1 replication. In fact, infection with VSV-pseudotyped HIV-1 virions and fusion of BlaM-Vpr-containing HIV-1 viruses with activated PBMCs in the presence of Dasatinib suggested that Dasatinib was not acting at fusion level. Finally, PBMCs from patients on chronic treatment with Dasatinib showed lower level of SAMHD1 phosphorylation in response to activating stimuli and low susceptibility to HIV-1 infection ex vivo. Consequently, Dasatinib is a compound currently used in clinic that preserves the antiviral function of SAMHD1. Using Dasatinib as adjuvant of antiretroviral therapy during early primary HIV-1 infection would contribute to reduce viral replication and spread, prevent reservoir seeding, and preserve CD4 counts and CTL responses. These events would create a more favorable virologic and immunologic environment for future interventional studies aiming at HIV-1 eradication.
    No preview · Article · Feb 2016 · Biochemical pharmacology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia.
    Full-text · Article · Dec 2015 · PLoS Pathogens
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The causes of HIV-vaccines failure are poorly understood. Therapeutic vaccination with MVA-B in HIV-1 infected individuals did not control the virus upon analytical treatment interruption (ATI). We investigated whether the functional characteristics of HIV-specific CD8 T-cell responses stimulated by this vaccine, and the level of exhaustion of these cells might explain these results. Methods: Twenty-one HIV-1 chronically-infected patients on cART, included in the therapeutic vaccine trial RISVAC03, were studied: 13 immunized and 8 controls. Functional characteristics, cytotoxic potential and exhaustion of HIV-specific CD8 T-cells, were evaluated by polychromatic flow cytometry. Differences between groups were tested using non-parametric tests. Results: MVA-B vaccine induced an increase in HIV-specific CD8 T-cells response, but also increased their levels of exhaustion. At week 18 (following 3 immunizations) the level of response increased with respect to baseline (p = 0.02). A significant increase at weeks 18 and 24 (ATI) in GranzymeB content was also observed. Interestingly, it was found an increase in expression of exhaustion markers at weeks 18 (p = 0.006) and 24 (p = 0.01). However, there was no significant change in the functional profile of vaccine-induced CD8 cells. At week 36, in parallel to the rebound of plasma viremia after 12 weeks ATI, a significant increase in the level of CD8 response, in GrzB content and in exhaustion markers expression, was observed in both groups. Conclusions: We show that therapeutic vaccination with MVA-B tilts the balance between activation and regulation of the response of HIV-specific CD8 T cells towards regulation, which impacts on the viral rebound after ATI.
    No preview · Article · Nov 2015 · AIDS (London, England)
  • [Show abstract] [Hide abstract]
    ABSTRACT: Importance: Protective effects of HLA-B*13 on HIV-1 disease progression are mediated in part by fitness costs of CTL escape mutations in conserved Gag epitopes, but other mechanisms remain incompletely known. We extend our knowledge of the impact of B*13-driven escape on HIV-1 replication by identifying Gag-K436R as a compensatory mutation for the fitness-costly Gag-I437L. We also identify Gag-I147L, the most rapidly and commonly selected B*13-driven substitution in HIV-1, as a putative C-terminal anchor residue mutation in a novel B*13 epitope. Most notably, we identify a novel escape-driven fitness defect: B*13-driven substitutions E24Q and Q107R in Nef, when present together, substantially impair this protein's ability to downregulate HLA class I. This in turn increases the visibility of infected cells to HIV-specific T-cells. Our results suggest that B*13-associated escape mutations impair HIV-1 replication by two distinct mechanisms - by reducing Gag fitness and dampening Nef immune evasion function.
    No preview · Article · Sep 2015 · Journal of Virology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. Methods: Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after 'final stop', compared between groups. Results: Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). Conclusions: STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials. Trial registration: ClinicalTrials.gov NCT02300623.
    Full-text · Article · Jul 2015 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This article aims to investigate if the detection of preexisting drug-resistant minority variant (DRMV) and/or X4 HIV-1 variants could improve the efficacy of first-line combined antiretroviral therapy (ART) in late presenters. Post-hoc, combined analysis of two open-label, prospective, randomized clinical trials comparing first-line ART with efavirenz (EFV) vs. ritonavir-boosted protease inhibitor (PI/r)-based regimens in ART-naive, HIV-1-infected patients, with CD4 T-cell counts less than 100 cells/μl and wild-type HIV-1 by bulk sequencing. Pre-ART samples were reanalyzed for the presence of DRMVs and X4 HIV-1 using 454 sequencing. Kaplan-Meier curves and Cox regression were used to evaluate the association between X4 HIV and DRMVs and risk of virological failure. From 141 evaluable patients, 57 received EFV, and 84 received PI/r, including first-line ART. Median pre-ART CD4 T-cell counts and HIV-1 RNA levels were 39 cells/μl and 257 424 copies/ml, respectively; 35.5% of patients had X4 HIV variants. Detection of DRMVs leading to an ART-specific cumulative HIVdb score of at least 10 increased the risk of virological failure in patients initiating EFV [log-rank P = 0.048, hazard ratio = 4.3 (95% confidence interval: 0.8, 25.0), P = 0.074], but not in those starting PI/r. Presence of X4 HIV did not affect virological outcomes, but was associated with impaired CD4 T-cell count recovery over 2 years (214 vs. 315 cells/μl with X4 vs. R5 HIV-1 tropism, respectively, P = 0.017). Accounting for preexisting DRMVs may improve the outcomes of first-line nonnucleoside reverse transcriptase inhibitor-based ART in late presenters with advanced immune suppression. Presence of X4 HIV-1 at diagnosis predicts impaired immune restoration under ART.
    Full-text · Article · Jul 2015 · AIDS
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although virus-specific responses are rarely detected by conventional approaches, we report here the detection of T-cell responses in HIV-exposed seronegative (HESN) patients by two distinct assays. HIV-specific T-cell responses were analyzed by enzyme-linked immunospot in peripheral blood mononuclear cells from HESN patients after a 48-h co-culture with boosted dendritic cells. Additionally, a boosted flow cytometry approach was used to capture antiviral T-cell responses. Host genetic factors and T-cell activation were also analyzed to assess their implication on HIV exposure. Of the 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-positive 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 populations. The combined use of our boosted dendritic cell technique with a boosted flow cytometric approach allows us both to detect specific HIV-positive responses in a higher percentage of HESN patients and to define specific effector function profiles. This study contributes to a better understanding of resistance to HIV infection.
    No preview · Article · Jun 2015 · AIDS (London, England)
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the availability of effective combined antiretroviral treatment, many patients still present with advanced HIV infection, often accompanied by an AIDS-defining disease. A subgroup of patients starting antiretroviral treatment under these clinical conditions may experience paradoxical worsening of their disease as a result of an exaggerated immune response towards an active (but also subclinical) infectious agent, despite an appropriate virological and immunological response to the treatment. This clinical condition, known as immune reconstitution inflammatory syndrome, may cause significant morbidity and even mortality if it is not promptly recognized and treated. This review updates current knowledge about the incidence, diagnostic criteria, risk factors, clinical manifestations, and management of opportunistic infections and immune reconstitution inflammatory syndrome in the combined antiretroviral treatment era.
    No preview · Article · Apr 2015 · Expert Review of Anti-infective Therapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 infection cannot be cured due to reservoirs formed early after infection. Decreasing the massive CD4+ T cell activation that occurs at the beginning of the disease would delay reservoir seeding, providing a better prognosis for patients. CD4+ T cell activation is mediated by protein kinase C (PKC) theta (θ), which is involved in T-cell proliferation, as well as NF-κB, NF-AT, and AP-1 activation. We found that PKCθ activity increased viral replication, but also that HIV-1 induced higher activation of PKCθ in infected CD4+ T cells, creating a feedback loop. Therefore, specific inhibition of PKCθ activity could contribute to control HIV-1 replication. We tested the efficacy of seven PKCθ specific inhibitors to control HIV-1 replication in CD4+ T cells and selected two of the more potent and safer: CGX1079 and CGX0471. They reduced PKCθ phosphorylation at T538 and its translocation to the plasma membrane, which correlated with decreased HIV-1 retrotranscription through partial inhibition of SAMHD1 antiviral activity, rendering lower proviral integration. CGX1079 and CGX0471 also interfered with viral transcription, which would reduce the production of new virions, as well as the subsequent spread and infection of new targets that would increase the reservoir size. CGX1079 and CGX0471 did not completely abrogate T-cell functions such as proliferation and CD8-mediated release of IFNγ in PBMCs from HIV-infected patients, thereby avoiding general immunosuppresion. Consequently, using PKCθ inhibitors as adjuvant of antiretroviral therapy in recently infected patients would decrease the pool of activated CD4(+) T cells, thwarting proviral integration and reducing the reservoir size. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Feb 2015 · Biochemical Pharmacology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed. HIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466. MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/10(6) PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P = 0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment. MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1-infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram. © 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 · Feb 2015 · Journal of Antimicrobial Chemotherapy
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Few randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naïve, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens. Randomized, controlled, open-label multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naïve patients with <100 CD4 cells/mm were randomly assigned in a 1:1:1 ratio to efavirenz (n=29), atazanavir/ritonavir (n=30), or lopinavir/ritonavir (n=30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary endpoints were the proportion of patients with HIV-1 RNA <50 copies/mL, adverse events, disease progression, and death. In the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was +193 (129-349) cells/µL in the efavirenz arm, +197 (146-238) cells/µL in the ritonavir-boosted atazanavir arm, and +205 (178-327) cells/µL in the ritonavir-boosted lopinavir arm (P=0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks (efavirenz, 85.71% [95%CI, 68.5-94.3]; atazanavir, 80% [95%CI, 62.7-90.5]; and lopinavir, 82.8% [95%CI, 65.5-92.4]; p=0.88). Bacterial translocation, inflammation, immune activation, and apoptotic markers-but not D-dimer-declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died. The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).
    Full-text · Article · Feb 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the antiretroviral therapy has led to a long-term control of HIV-1, it does not cure the disease. Therefore, several strategies are being explored to develop an effective HIV vaccine, such as the use of dendritic cells (DCs). DC-based immunotherapies bear different limitations, but one of the most critical point is the antigen loading into DCs. Nanotechnology offers new tools to overcome these constraints. Dendrimers have been proposed as carriers for targeted delivery of HIV antigens in DCs. These nanosystems can release the antigens in a controlled manner leading to a more potent specific immune response. This review focuses on the first steps for clinical development of dendrimers to assess their safety and potential use in DC-based immunotherapies against HIV.
    Full-text · Article · Dec 2014 · Nanomedicine
  • Source

    Preview · Article · Oct 2014 · AIDS Research and Human Retroviruses

  • No preview · Article · Oct 2014 · AIDS Research and Human Retroviruses
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation. Methods We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed. Results CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01). Conclusions Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.
    Full-text · Article · Sep 2014 · Journal of the International AIDS Society
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers Results After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200 cp/ml) and 5 uninfected individuals (HIV-) through TaqMan Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs became significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. Conclusions Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.
    Full-text · Article · Sep 2014 · PLoS ONE

Publication Stats

2k Citations
612.25 Total Impact Points

Institutions

  • 2015
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 2005-2015
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 1991-2015
    • Hospital Clínic de Barcelona
      • • Servicio de Enfermedades Infecciosas
      • • Servicio de Hematología
      Barcino, Catalonia, Spain
  • 1982-2015
    • University of Barcelona
      • • Department of Medicine
      • • Department of Geochemistry, Petrology and Geological Prospecting
      Barcino, Catalonia, Spain
  • 1983-2008
    • Autonomous University of Barcelona
      • • Department of Biochemistry and Molecular Biology
      • • Faculty of Sciences
      • • Department of Chemistry
      Cerdanyola del Vallès, Catalonia, Spain
  • 2004
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 2003
    • University of California, San Francisco
      San Francisco, California, United States