PMPA is a nucleotide analogue with invitro activity against HIV-1, HIV-2, and hepatitis B virus. The active intracellular metabolite, PMPA diphosphate (PMPApp), inhibits HIV-1 reverse transcriptase at concentrations about 200-fold lower than that needed to inhibit DNA polymerase alpha. The in vivo half-life of PMPApp in peripheral blood mononuclear cells and lymph nodes from monkeys injected with one dose of PMPA was greater that 24 hours. The objectives of this study are to (a) evaluate the safety of single and multiple doses of PMPA Prodrug when administered orally to HIV-infected subjects, (b) to evaluate the pharmacokinetics of single and multiple doses of PMPA Prodrug, and (c) to evaluate the anti-HIV effect of PMPA Prodrug as demonstrated by effects on CD4 count and HIV RNA.
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