translation agency

A phase I/II study of 9-(2-phosphonylmethoxyethyl) adenine (PMEA) in advanced HIV infection.
Collier AC; Coombs RW; Nienow J; Paradise M; Yang HH; Troxel S; Boggs J;
December 30, 1995
Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:158.

Objective: To evaluate safety, tolerance, pharmacokinetics, and anti-HIV activity of intravenous PMEA, a new nucleotide analogue reverse transcriptase inhibitor. Methods: Open- label, dose-escalation study of 5 subjects per group, given 1,3 or 10 mg/kg/day for 4 weeks, with an optional treatment extension. Blinded quantitative virologic assays, including HIV RNA (branched DNA assay, Chiron) and PBMC microculture were done. Results: Eight subjects (7 male/1 female, median CD4 count 42/mm3, median [25-75th percentile] ICD HIV p24 antigen 150[77-222]pg/ml, HIV infectious units/million PBMCs[IUPM] of 128[16-206], and HIV RNA equivalents/ml of plasma [EPM, n=6] of 93,000 [74,000-119,000]) on no (n=3) or stable antiretroviral therapy (n=5) have been enrolled in an ongoing trial. Current follow-up is 2-17 weeks. Serum PMEA levels are pending. One subject (1 mg/kg) has terminated early 2 degrees to increased transaminases; 3 others (at 3 mg/kg) have had dose interruptions/decreases 2 degrees to neutropenia and/or increased transaminases. One other had transient urethral ulceration. CD4 cell counts were unchanged. At week 4, the median for virologic parameters were: 76 pg/ml ICD p24, 93 IUPM, and 112,000 RNA EPM (Wilcoxon signed-rank, P=NS for each results). Conclusion: In subjects with advanced HIV, high viral burden, extensive prior antiretroviral treatment, and numerous concomitant medications, potential toxicity and antiviral activity were observed for PMEA. Additional data from this ongoing study will be presented.

Adenine/ANALOGS & DERIVATIVES/PHARMACOKINETICS/*THERAPEUTIC USE Antiviral Agents/PHARMACOKINETICS/*THERAPEUTIC USE Clinical Trials Clinical Trials, Phase I Clinical Trials, Phase II Drug Tolerance Female Human HIV Infections/*DRUG THERAPY Injections, Intravenous Male ABSTRACT