Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • br Conclusions The following are the supplementary

    2018-10-23


    Conclusions The following are the supplementary data related to this article.
    Author Contributions
    Conflict of Interest
    Acknowledgements This work was supported by the Health Research Institute of University Hospital Clínico San Carlos, “Generalitat Valenciana” (PROMETEOII/2014/065), by the Spanish Ministry of Economy and Competitiveness (SAF2012-31187, SAF2013-49788-EXP, SAF2015-65878 from MINECO), Instituto de Salud Carlos III (PIE14-00045 and Redes Temáticas de Investigación en SIDA RETICRD12/0017/0029 and RD12/0017/0037), and the Junta de Andalucía (Proyecto de Excelencia CTS-6313). The present investigation was also funded by the Spanish Ministry of Economy and Competitiveness and the Federal Ministry of Education and Research (BMBF) within the ERA NET PathoGenoMics2 program, grant number 0315441A. This work was further funded by grants BIO2011-25012 and BIO2014-54494-R from the Spanish Ministry of Economy and Competitiveness. The authors gratefully acknowledge the financial support provided by the European Regional Development Fund (ERDF). C.B and D.R would like to acknowledge funding from the Spanish Ministry of Economy and Competitiveness (CTQ2014-55279-R). J.F.V.C. was supported by a fellowship “Ayudas Predoctorales de Formación en Investigación en Salud” from the Instituto de Salud Carlos III (Spain) and the CONACYT-SECITI (México). S.S.V. is supported by a grant from the Spanish Ministry of Science and Innovation (Contratos Juan Rodés, ECC/1051/2013), and T.S. is supported by a grant from the European Society of Pediatric Infectious Diseases (ESPID). Funding Agencies did not have any role neither in the writing of the manuscript or the decision to submit it Solamargine nor have paid to write this article. The authors wish to acknowledge the participation of all of the study participants who contributed to this work as well as the clinical research staff of the participating institutions who made this research possible.
    Introduction Latently infected CD4+ T cells are the major barrier to HIV-1 cure efforts. The cells contain integrated proviruses that are transcriptionally silent and thus able to evade detection and clearance by the immune system. The shock-and-kill cure strategy seeks to first reactivate these latent viruses without causing global T cell activation followed by clearance of the reactivated cells by the immune system (reviewed in Siliciano and Siliciano, 2013; Archin and Margolis, 2014). Latency reactivating agents (LRAs) are drugs that induce HIV-1 transcription. Notable drug classes include PKC agonists and HDAC inhibitors (HDACi), which have been very effective in inducing HIV-1 transcription in cell lines (Contreras et al., 2009; Xing et al., 2011; Li et al., 2013; DeChristopher et al., 2012). Unfortunately, in vitro experiments with primary resting CD4 T cells from patients on suppressive antiretroviral therapy (ART) regimens suggest that most individual LRAs are unable to induce substantive amounts of HIV-1 transcription with the notable exception of PKC agonists bryostatin-1-1 (Bullen et al., 2014) and ingenol (Spivak et al., 2015). However, LRA combinations in the same system are capable of inducing significant HIV-1 transcription (Laird et al., 2015; Jiang et al., 2015; Darcis et al., 2015). The other half of the cure strategy deals with killing newly reactivated infected CD4+ T cells. Recent experiments suggest that reactivation from latency is not enough to induce cell death (Shan et al., 2012), and therefore there may be a need for immune mediated eradication. Expanded CD8+ T cell lines were able to clear reactivated latently infected resting CD4+ T cells following exposure to the HDAC inhibitor, vorinostat (Sung et al., 2015). However primary CD8+ T cells from patients on suppressive ART regimens that were pre-stimulated with overlapping Gag peptides were unable to consistently reduce the amount of HIV-1 mRNA induced from autologous resting CD4+ T cells that were activated with PMA and ionomycin (Walker-Sperling et al., 2015).