PREVENTION OF MURINE AIDS DEVELOPMENT BY (R)-9-(2-PHOSPHONYLMETHOXYPROPYL)ADENINE

LP-BM5 murine leukemia virus (MuLV) infection causes severe immunodefi ciency termed murine AIDS (MAIDS). The acyclic nucleoside phosphonates (R)-9-(2-phosphonylmethosypropyl)adenine (PMPA) and 9-(2-phosphonylme thoxyethyl)adenine (PMEA) were examined, in comparison with zidovudine (AZT), for their inhibitory effect on the development of MAIDS. Altho ugh no significant difference in inhibition of LP-BM5 MuLV replication was identified between PMPA and PMEA in cell cultures, PMPA was obvio usly less cytotoxic to the host lymphocytes. None of the mice treated in vivo with 5 or 25 mg/kg of PMPA or 25 mg/kg of PMEA developed MAIDS at 5 weeks after viral infection. However at 9 weeks, none of the 25 mg/kg PMPA-treated mice progressed to MAIDS? except for one that devel oped mild MAIDS, whereas PMEA, even at 100 mg/kg, could not prevent di sease progression. MAIDS-associated activation of lymphocytes and vira l replication were drastically inhibited by PMPA treatment. These resu lts indicate that PMPA is a highly effective antiretroviral agent in v ivo.