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. 1998 Jun;42(6):1484-7.
doi: 10.1128/AAC.42.6.1484.

Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains

R V Srinivas  1 , A Fridland
Affiliations

Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl)PMPA against various drug-resistant human immunodeficiency virus strains

R V Srinivas et al. Antimicrob Agents Chemother. 1998 Jun.

Abstract

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.

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Figures

FIG. 1
FIG. 1
Inhibition of virion-associated RT activity by PMPApp. Two independent experiments were done in triplicate with different PMPApp concentration ranges. The results (mean ± standard deviation) of one experiment are presented. The values are indicated as percentage of the control RT activity. The amount of radioactivity incorporated in the control was 8.1 × 105 cpm for K65R virus and 1.5 × 106 cpm for HIV-1IIIB.
See this image and copyright information in PMC

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