作者
Fathima Nuzra Nagoor Pitchai,Elizabeth J. Tanner,Neha Khetan,Gustavo Vasen,Clara Levrel,Arjun J. Kumar,Shilpi Pandey,Tracy Cheever,Philip Barnette,David A. Spencer,Seungyong Jung,Joshua Glazier,Cassandra E. Thompson,Richard S. Garfein,Hye-In Son,Hye-In Son,Steffanie A. Strathdee,Leo Holguin,Ryan Urak,John Burnett,William Burgess,Kathleen Busman‐Sahay,Jacob D. Estes,Ann J. Hessell,Christine M. Fennessey,Brandon F. Keele,Nancy L. Haigwood,Leor S. Weinberger
摘要
Antiviral therapies with reduced frequencies of administration and high barriers to resistance remain a major goal. For HIV, theories have proposed that viral-deletion variants, which conditionally replicate with a basic reproductive ratio [R 0 ] > 1 (termed “therapeutic interfering particles” or “TIPs”), could parasitize wild-type virus to constitute single-administration, escape-resistant antiviral therapies. We report the engineering of a TIP that, in rhesus macaques, reduces viremia of a highly pathogenic model of HIV by >3log 10 following a single intravenous injection. Animal lifespan was significantly extended, TIPs conditionally replicated and were continually detected for >6 months, and sequencing data showed no evidence of viral escape. A single TIP injection also suppressed virus replication in humanized mice and cells from persons living with HIV. These data provide proof of concept for a potential new class of single-administration antiviral therapies.