Immune responses may make HIV-1 therapeutic interfering particles less effective

Abstract

The current standard treatment for HIV-1 infection is antiretroviral therapy, which effectively suppresses viral replication but requires a lifelong drug regimen. An alternative treatment approach is a single injection of a modified version of the HIV-1 virus, termed a therapeutic interfering particle (TIP), that lacks replication machinery and suppresses the wild-type virus by competing for viral proteins. Here, we derive a novel ordinary differential equation model of TIP dynamics. We confirm results from previous models that TIPs can reduce viral load when doubly infected cells produce at least as many virus particles as singly infected cells. By deriving the basic reproduction number R0T of a TIP, we predict that concurrent antiretroviral therapy should make it more difficult for a TIP to persist in a host. Adding an immune response to our model reveals that even a moderate immune response against virally infected cells drastically decreases the range of parameter values for which therapy is effective. Together, these results show that the success of TIPs depend on the properties of the wild-type virus and even more strongly on the immune response, which makes it hard to predict therapeutic success.