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null AIDS Research Unit
Hospital Universitario Vall d'Hebron (Barcelona)

Description

The AIDS Research Unit of Hospital Universitari Vall d’Hebron is composed by >20 professionals (infectious diseases physicians, pediatricians, virologist, immunologist, pre/post-doctoral research fellows, nurses, psychologist, clinical trials support team).

The group has been involved in HIV research since 1981 and has an HIV outpatient clinic (>2,500 patients), being able to carry out clinical trials phase II-IV, including pharmacokinetic (PK) studies with LC/MS. The group participates in national/international HIV cohorts. Between 2011 and 2017 we have published >120 articles and participated in >70 trials. We have risen >1.500.000 € in grant funding, both public and private.

Main focuses of interest are:

  • Antiretroviral therapy (ART) in naïve, and pretreated patients
  • Co-morbidities
  • Opportunistic infections
  • Hepatitis C virus (HCV)
  • Pharmacokinetics (PK) of ART, with LC-MS/MS Acquity UPLC-XEVO, Waters®

Recently, two new lines of research have been consolidated in our clinical group:

  • The first is anal dysplasia related to the human papillomavirus (HPV) in patients with HIV infection, with clinical activity (Anal Dysplasia Screening Unit), research (5 articles published in high impact journals and the HPV chapter of the SEIMC-GeITS ITS guidelines) and teaching (organizing training courses and teaching specialists at our unit). 
  • The second line is sexually transmitted infections (STIs). The STI Unit of Drassanes, one of the largest in the country, has become part of our department and this opens the possibility to research in STIs both in patients with STI-HIV co-infection and people at high risk of acquiring HIV.

Our “HIV Translational Laboratory” was set up in 2015 at the Vall d´Hebron Research Institute, under the leadership of Maria J. Buzón. Our scientific interest is focused on characterization and targeting of HIV reservoirs that persist in patients successfully treated with antiretroviral treatment (ART).  More specifically, the current research of the lab is focused on:

  • Characterizing the cellular reservoirs that maintain HIV in ART-treated patients.  The establishment of viral latency in cells represents the main barrier for an HIV cure. Then, the identification and characterization of the viral reservoirs are extremely important for the design of new targeted therapies directed to deplete the specific latent reservoirs.  In this line of investigation, we focus on identifying what CD4 T cell subsets are able to sustain the HIV viral reservoir in patients that have been treated with ART for prolonged periods of time.
  • Assessing the impact of new drugs to purge the latent reservoir. The use of latency reversal agents (LRAs) has been recently pursued as a strategy to reduce the latent HIV reservoir. However, its effectiveness in clinical trials has been hampered by the inability of these compounds to effectively impact the latent HIV reservoir. One possible explanation for this failure might be the inadequate reactivation of HIV by LRAs from long-lived resting CD4 T cells, the most dominant niche for latent HIV. In this line of investigation, we are identifying and extensively analyzing which LRAs, and their combinations, are able to induce the expression of HIV from long-lived latently infected CD4 T cells.
  • Exploring new synergistic approaches to deplete the latent reservoir with bi-specific nanoparticles. Natural Killer (NK) cells have been associated with changes on HIV-1 DNA after the in vivo administration of LRAs. In this research we are proposing for the first time, an entirely novel combined-approach to specifically re-direct the killing of HIV-1 infected cells after the pharmacological induction of HIV expression. In order to do so, we are designing bi-specific nanoparticles coupled with antibodies that recognize simultaneously viral proteins expressed on the surface of the HIV-1 infected cells and cytotoxic immune NK cells. This entirely new shock and kill combined-approach will merge the advantage of a targeted-immune therapy with the use of currently available LRAs.;
  • Targeting specific sites of viral persistence. The evidence of ongoing viral replication in different body compartments despite ART represents a substantial barrier to achieve an HIV cure. In particular, B cell follicles within the lymph nodes have been pointed out as one of the main viral sanctuary site where HIV might be invisible to the action of the immune system and to different antiretroviral drugs. Therefore, there is an urgent need for novel therapeutic strategies that specifically target lymphatic tissues. In this regard, we are developing and validating an innovative approach that will specifically target the site of viral persistence. This approximation will give us the possibility to deliver antiretroviral drugs, immune activators or latency reversal agents, among others compounds, to the specific site of HIV persistence.

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Members

Esteban Ribera
Joaquín Burgos
María José Buzón
Estrella Caballero
Adrian Curran
Vicenç Falcó
Jordi Navarro
Imma Ocaña
Pere Soler

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Publications

  • The role of oncogenic human papillomavirus determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM. 
    Burgos J, Hernández-Losa J, Landolfi S, Guelar A, Dinares M, Villar J, Navarro J, Ribera E, Falcó V, Curran A.  AIDS. 2017 Oct 23;31(16):2227-2233. doi:10.1097/ QAD.0000000000001605. PubMed PMID: 28723712. 
  • Dual therapy with darunavir and ritonavir plus lamivudine versus triple therapy with darunavir and ritonavir plus tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine for maintenance of HIV-1 viral suppression: randomised, open label, non-inferiority DUAL-GESIDA 8014-RIS-EST45 trial. 
    Pulido F, Ribera E, Lagarde M, Pérez-Valero I, Palacios R, Iribarren JA, Payeras A, Domingo P, Sanz J, Cervero M, Curran A, Rodríguez-Gómez FJ, Téllez MJ, Ryan P, Barrufet P, Knobel H, Rivero A, Alejos B, Yllescas M, Arribas JR; DUAL-GESIDA-8014-RIS-EST45 Study Group.  Clin Infect Dis. 2017 Aug 17. doi: 10.1093/cid/cix734. [Epub ahead of print] PubMed PMID: 29020293. 
  • Effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen for the treatment of HIV-1 infection in naive patients. 
    Curran A, Rojas J, Cabello A, Troya J, Imaz A, Domingo P, Martinez E, Ryan P, Górgolas M, Podzamczer D, Knobel H, Gutiérrez F, Ribera E.  J Antimicrob Chemother. 2016 Dec;71(12):3510-3514. Epub 2016 Sep 2. PubMed PMID: 27591292. 
  • Darunavir and ritonavir total and unbound plasmatic concentrations in HIV-HCV-coinfected patients with hepatic cirrhosis compared to those in HIV-monoinfected patients. 
    Curran A, Martí R, López RM, Pérez M, Crespo M, Melià MJ, Navarro J, Burgos J, Falcó V, Ocaña I, Ribera E.  D Antimicrob Agents Chemother. 2015 Nov;59(11):6782-90. doi: 10.1128/AAC.01099-15. Epub 2015 Aug 17. PubMed PMID: 26282411; PubMed Central PMCID: PMC4604348. 
  • Tenofovir/ emtricitabine inflUence on LIPid metabolism (TULIP) Study Group. The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial. 
    Santos JR, Saumoy M, Curran A, Bravo I, Llibre JM, Navarro J, Estany C, Podzamczer D, Ribera E, Negredo E, Clotet B, Paredes R.  Clin Infect Dis. 2015 Aug 1;61(3):403-8. doi: 10.1093/cid/civ296. Epub 2015 Apr 13. PubMed PMID: 25870325. 
  • Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected MSM. 
    Burgos J, Curran A, Tallada N, Guelar A, Navarro J, Landolfi S, Villar J, Crespo M, Ribera E, Falcó V.  AIDS. 2015 Mar 27;29(6):695-702. doi: 10.1097/QAD.0000000000000603. PubMed PMID: 25849833. 
  • Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: a randomized clinical trial. 
    Martinez E, Gonzalez-Cordon A, Ferrer E, Domingo P, Negredo E, Gutierrez F, Portilla J, Curran A, Podzamczer D, Ribera E, Murillas J, Bernardino JI, Santos I, Carton JA, Peraire J, Pich J, Deulofeu R, Perez I, Gatell JM; ATADAR Study Group.  Clin Infect Dis. 2015 Mar 1;60(5):811-20. doi: 10.1093/cid/ciu898. Epub 2014 Nov 10. PubMed PMID: 25389256. 
  • HIV-1 persistence in CD4+ T cells with stem cell-like properties. 
    Buzon MJ, Sun H, Li C, Shaw A, Seiss K, Ouyang Z, Martin-Gayo E, Leng J, Henrich TJ, Li JZ, Pereyra F, Zurakowski R, Walker BD, Rosenberg ES, Yu XG, Lichterfeld M.  Nat Med. 2014 Feb;20(2):139-42. doi: 10.1038/nm.3445. Epub 2014 Jan 12. PubMed PMID: 24412925; PubMed Central PMCID: PMC3959167. 
  • Impact of switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the RECOMB study. 
    Ribera E, Larrousse M, Curran A, Negredo E, Clotet B, Estrada V, Sanz J, Berenguer J, Rubio R, Pulido F, Ferrer P, Alvarez ML, Arterburn S, Martínez E.  HIV Med. 2013 Jul;14(6):327-36. doi: 10.1111/hiv.12011. Epub 2013 Jan 9. PubMed PMID: 23298339. 
  • HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. 
    Buzón MJ, Massanella M, Llibre JM, Esteve A, Dahl V, Puertas MC, Gatell JM, Domingo P, Paredes R, Sharkey M, Palmer S, Stevenson M, Clotet B, Blanco J, Martinez-Picado J.  Nat Med. 2010 Apr;16(4):460-5. doi: 10.1038/nm.2111. Epub 2010 Mar 14. PubMed PMID: 20228817. 

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