Current approaches to treatment of HIV infection include nucleoside analogues and protease inhibitors. Despite the improved activity of combination therapy over monotherapies as measured by effects on surrogate markers or disease progression, the immunologic and clinical impact of such therapies is incomplete and transient. Development of in vitro resistance has been demonstrated in HIV isolates from treated patients. Therefore the identification of novel drugs with improved activity, tolerability, and resistance profiles for treating patients with HIV infection are still needed. PMPA is a nucleotide analogue with in vitro 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 PNWApp in peripheral blood mononuclear cells and lymph nodes from monkeys injected with one dose of PMPA was greater than 24 hours. The objective of this proposed study are to (a) elevate the safety of single and multiple doses of PMPA Prodrug when administered orally to HIV-nfected subjects (b) to evaluate the pharmacokinetics of single and multiple doses of PMPA Prodrug as demonstrated by effects on CD4 count and HIV RNA.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
3M01RR000052-38S1
Application #
6297572
Study Section
Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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