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