ANTIRETROVIRUS ACTIVITY OF 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE (PMEA) INVIVO INCREASES WHEN IT IS LESS FREQUENTLY ADMINISTERED

Different treatment schedules have been investigated when evaluating the inhibitory effect of 9‐(2‐phosphonylmethoxyethyl)adenine (PMEA) and 3′ ‐azido‐2′, 3′ ‐dideoxythymidine (AZT) on the replication of human immunodeficiency virus type I (HIV‐1) in MT‐4 cells, transformation of C3H/3T3 cells by Moloney murine sarcoma virus (MSV), and MSV‐induced tumor formation in newborn NMRI mice. Shortening the exposure time of HIV‐1‐infected MT‐4 cells to PMEA or AZT led to an increase in the selectivity index of both compounds. PMEA proved markedly more efficient in suppressing MSV‐induced tumor formation in mice when administered as a single dose on the day of infection than when these doses were spread over 2, 4 or 7 administrations within 1 week after the virus infection. This was not observed when the total dose of AZT was fractionated. While the infrequent dosage regimen increased the anti‐retrovirus activity of PMEA, it did not increase its toxicity for the host. This unique property makes PMEA an attractive candidate for the treatment of retrovirus infections, including AIDS. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company