HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing.

TitleHIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing.
Publication TypeJournal Article
Year of Publication2023
AuthorsLyons, DE, Kumar, P, Roan, NR, Defechereux, PA, Feschotte, C, Lange, UC, Murthy, N, Sameshima, P, Verdin, E, Ake, JA, Parsons, MS, Nath, A, Gianella, S, Smith, DM, Kallas, EG, Villa, TJ, Strange, R, Mwesigwa, B, O'Brien, RLFurler, Nixon, DF, Ndhlovu, LC, Valente, ST, Ott, M
Date Published2023 Oct 28

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.

Alternate JournalViruses
PubMed ID38005849
PubMed Central IDPMC10674359
Grant ListUM1AI164559 / / National Institute of Allergy and Infectious Diseases /
K01OD031900 / / National Institutes of Health's Office of the Director /