Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

Online publication: 29/03/2013

Abstract:

 Antiretroviral therapy for HIV infection needs lifelong access and strict adherence to regimens that are both expensive and associated with toxic effects. A curative intervention will be needed to fully stop the epidemic. The failure to eradicate HIV infection during long-term antiretroviral therapy shows the intrinsic stability of the viral genome in latently infected CD4T cells and other cells, and possibly a sustained low-level viral replication. Heterogeneity in latently infected cell populations and homoeostatic proliferation of infected cells might affect the dynamics of virus production and persistence. Despite potent antiretroviral therapy, chronic immune activation, inflammation, and immune dysfunction persist, and are likely to have important effects on the size and distribution of the viral reservoir. The inability of the immune system to recognise cells harbouring latent virus and to eliminate cells actively producing virus is the biggest challenge to finding a cure. We look at new approaches to unravelling the complex virus-host interactions that lead to persistent infection and latency, and discuss the rationale for combination of novel treatment strategies with available antiretroviral treatment options to cure HIV. 

Authors: Prof Christine Katlama MD a, Steven G Deeks MD b, Prof Brigitte Autran PhD c, Prof Javier Martinez-Picado PhD d, Prof Jan van Lunzen MD e, Prof Christine Rouzioux MD f, Michael Miller PhD g, Stefano Vella MD h, Prof Joern E Schmitz PhD i, Jeffrey Ahlers PhD k, Douglas D Richman MD j, Dr Rafick P Sekaly PhD k  a Department of Infectious Diseases, Pierre and Marie Curie University, Pitié-Salpêtriere Hospital, Paris, Franceb Department of Medicine, University of California, San Francisco, CA, USAc Laboratory of Immunity and Infection, Pierre and Marie Curie University, Hospital Pitié-Salpêtriere, Paris, Franced AIDS Research Institute IrsiCaixa, ICREA and Universitat Autònoma de Barcelona, Badalona, Spaine Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germanyf Department of Virology, Paris-Descartes University Necker Hospital, Paris, Franceg Department of West Point Discovery Chemistry, Merck Research Laboratories, West Point, PA, USAh Department of Pharmacology and Therapeutic Research, Superior Health Institute, Rome, Italyi Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USAj VA San Diego Healthcare System and Departments of Pathology and Medicine, Center for AIDS Research, University of California, San Diego, CA, USAk Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, FL, USA Correspondence to: Dr Rafick P Sekaly, Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, FL 34987, USA Correspondence to: Dr Rafick P Sekaly, Vaccine and Gene Therapy Institute of Florida, Port Saint Lucie, FL 34987, USA rpsekaly@vgtifl.org Read abstract online in The Lancet  
  • Doi Code: Lancet. 2013 Mar 28. pii: S0140-6736(13)60104-X. doi: 10.1016/S0140-6736(13)60104-X

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