Inhibition of SIV and HIV-2 replication in cynomolgus monkeys by (-)9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G)

The antiherpes compound (-)9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) has been found to suppress the multiplication of SIVsm 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 3x10 mg kg(-1) day(-1) and higher, when H2G was given subcutaneously. These effects of H2G on SIVsm 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 3x10 mg kg(-1) day(-1) of H2G. The enantiomeric mixture (+/-)H2G at 3x25 mg kg(-1) day(-1) also delayed the appearance of SIVsm antigen but the (+)enantiomer of H2G at 3x10 mg kg(-1) day(-1) had no effect on primary SIVsm 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 3x25 mg kg(-1) day(-1) for 10 days.