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Antimicrobial Agents and Chemotherapy, June 1998, p. 1484-1487, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antiviral Activities of 9-R-2-Phosphonomethoxypropyl Adenine (PMPA) and Bis(isopropyloxymethylcarbonyl)PMPA against Various Drug-Resistant Human Immunodeficiency Virus Strains

Ranga V. Srinivas1,* and Arnold Fridland1,2

Department of Infectious Diseases, St. Jude Children's Research Hospital,1 and Department of Pharmacology, University of Tennessee,2 Memphis, Tennessee

Received 31 October 1997/Returned for modification 12 January 1998/Accepted 13 March 1998

9-R-2-Phosphonomethoxypropyl adenine (PMPA) is an acyclic nucleoside phosphonate analog that has demonstrated efficacy against human immunodeficiency virus (HIV). We recently described the synthesis, metabolism, and biological activities of bis(isopropyloxymethylcarbonyl)PMPA [bis(poc)PMPA] as an orally bioavailable prodrug for PMPA. Among a large panel of drug-resistant HIV type 1 variants, only the K65R virus was resistant to PMPA. K65R virus also showed reduced susceptibility to bis(poc)PMPA, although the prodrug could still inhibit these viruses at submicromolar, nontoxic concentrations. Among a panel of seven primary clinical isolates from patients with diverse treatment histories, only one isolate showed reduced susceptibility to PMPA and was found to carry three mutations (M41L, T69N, R73K) in its reverse transcriptase catalytic domain.

* Corresponding author. Mailing address: Department of Infectious Diseases, SJCRH, 332 N. Lauderdale, Memphis, TN 38105. Phone: (901) 495-2359. Fax: (901) 495-3099. E-mail: rv.srinivas{at}stjude.org.

Antimicrobial Agents and Chemotherapy, June 1998, p. 1484-1487, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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