Most of the antiretrovirals in development represent additions to the currently available drug classes. KP-1461 belongs to a novel class of drugs — viral decay accelerators — that increase the mutation rate, with the goal of exceeding the virus’s error threshold and thereby decreasing replication. In a recent manufacturer-sponsored, phase IIa study, researchers evaluated the safety, tolerability, and efficacy of 4 months of oral KP-1461 (1600 mg twice daily).The study involved 24 HIV-infected patients who had not received antiretroviral therapy (ART) for 16 weeks (83% men; median age, 47.5; mean duration of HIV infection, 15 years; median baseline CD4 count, 429 cells/mm3; median viral load, 68,450 copies/mL). All had received nonsuppressive ART in the past or had documented HIV resistance to multiple ART classes, or both, and many had intolerance to available agents. Trough levels of KP-1461 during the study exceeded those previously shown in vitro to be associated with significant viral load declines. Twelve patients experienced possibly drug-related adverse events, most of them mild to moderate in severity. Two patients discontinued medications because of adverse events, and two died of causes unrelated to study medications. No significant effect on viral load, CD4-cell count, or drug-resistance pattern was seen among the 13 patients who completed 4 months of treatment. Comparison of viral sequences between 10 of these patients and controls revealed mutation-pattern changes consistent with the drug’s proposed mechanism of action.

Comment:These are small and early data; however, and despite some shortfalls (the choice of patients (not totally naive, and not typical experienced patients), unusual disposition of some of the study participants), these data should lead to larger studies to assess the true role of this treatment.

CITATION: Hicks C et al. Safety, tolerability, and efficacy of KP-1461 as monotherapy for 124 days in antiretroviral-experienced, HIV type-1 infected subjects. AIDS Res Hum Retroviruses 2013 Feb; 29:250.

Published in Journal Watch HIV/AIDS Clinical Care