HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
Danielle E. Lyons,
Priti Kumar,
Nadia R. Roan,
Patricia A. Defechereux,
Cedric Feschotte,
Ulrike C. Lange,
Niren Murthy,
Pauline Sameshima,
Eric Verdin,
Julie A. Ake,
Matthew S. Parsons,
Avindra Nath,
Sara Gianella,
Davey M. Smith,
Esper G. Kallas,
Thomas J. Villa,
Richard Strange,
Betty Mwesigwa,
Robert L. Furler O’Brien,
Douglas F. Nixon,
Lishomwa C. Ndhlovu,
Susana T. Valente,
Melanie Ott
Affiliations
Danielle E. Lyons
Gladstone Institute of Virology, Gladstone Institutes, San Francisco, CA 94158, USA
Priti Kumar
Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06510, USA
Nadia R. Roan
Gladstone Institute of Virology, Gladstone Institutes, San Francisco, CA 94158, USA
Patricia A. Defechereux
Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA
Cedric Feschotte
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Ulrike C. Lange
Leibniz Institute of Virology, 20251 Hamburg, Germany
Niren Murthy
Department of Bioengineering, University of California, Berkeley, CA 94720, USA
Pauline Sameshima
Faculty of Education, Lakehead University, Thunder Bay, ON P7B 5E1, Canada
Eric Verdin
Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA
Julie A. Ake
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Matthew S. Parsons
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Avindra Nath
Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20824, USA
Sara Gianella
Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA
Davey M. Smith
Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, CA 92093, USA
Esper G. Kallas
Department of Infectious and Parasitic Diseases, University of Sao Paulo, São Paulo 04023-900, Brazil
Thomas J. Villa
HOPE Martin Delaney Collaboratory for HIV Cure Research Community Engagement Ambassador, Washinton, DC 20004, USA
Richard Strange
HOPE Martin Delaney Collaboratory for HIV Cure Research Community Engagement Ambassador, Washinton, DC 20004, USA
Betty Mwesigwa
Research Department, Makerere University Walter Reed Project, Kampala P.O Box 7062, Uganda
Robert L. Furler O’Brien
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
Douglas F. Nixon
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
Lishomwa C. Ndhlovu
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
Susana T. Valente
Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA
Melanie Ott
Gladstone Institute of Virology, Gladstone Institutes, San Francisco, CA 94158, USA
Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.
