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
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...
October 28, 2023: Viruses