Abstract
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 [R0] > 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 >3log10 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.
