Inhibition of SIV and HIV-2 Replication in Cynomolgus Monkeys by (-)9-[4-Hydroxy-2-(Hydroxymethyl)-Butyl]Guanine (H2G)

Abstract

The antiherpes compound (-)9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) has been found to suppress the multiplication of SIV_sm and HIV-2 in cynomolgus monkeys. This was seen as a delay in the appearance of viral antigen in serum during the primary infection at drug concentrations of 3×10 mg kg⁻¹ day⁻¹ and higher, when H2G was given subcutaneously. These effects of H2G on SIV_sm and HIV-2 replication in monkeys were similar to those observed using the same dose of 3′-azidothymidine (AZT). A complete prevention of HIV-2 infection was observed in one of four animals treated with 3×10 mg kg⁻¹ day⁻¹ of H2G. The enantiomeric mixture (+)H2G at 3×25 mg kg⁻¹ day⁻¹ also delayed the appearance of SIV_sm antigen but the (+)enantiomer of H2G at 3×10 mg kg⁻¹ day⁻¹ had no effect on primary SIV_sm infection in monkeys, indicating that only the (−)enantiomer (H2G) was inhibitory and that this effect was not influenced by the presence of the (+)enantiomer. No adverse effects on blood chemistry or haematology were observed in monkeys given 25 mg kg⁻¹ day⁻¹ of H2G for 9 weeks or 3×25 mg kg⁻¹ day⁻¹ for 10 days.