Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461: "Overall, many RNA virus populations, including HIV, appear to exist near the brink of survivability [12], [13], as agents that disrupt the delicately balanced networks described above – by increasing the frequency of mutations in the HIV genome by as little as <2-fold – cause viral extinction in cell culture [14]–[17]. Similarly, small increases in viral mutation frequencies have been shown to be associated with population collapse in other viral systems, including Vesicular Stomatitis, polio, Hepatitis C, Hantaan and foot-and-mouth disease [18]–[25].

"We are studying the use of first-in-class nucleotide analogs that are incorporated by reverse transcriptase without leading to chain termination, yet base pair ambiguously and thus cause mutations, with the goal of eventually pushing the viral quasispecies beyond the brink of survivability in vivo. We term this approach to HIV therapy as “viral decay acceleration” (VDA)."