Characterization of SIV isolates from macaques treated with the nucleoside analog, 9-(2-phosphonylmethoxyethyl)adenine (PMEA).

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Characterization of SIV isolates from macaques treated with the nucleoside analog, 9-(2-phosphonylmethoxyethyl)adenine (PMEA).

Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 102. Unique Identifier : AIDSLINE PRIM11/94191595
Sabo A; Grant R; Follis K; Bischofberger N; Tsai CC; University of Washington Regional Primate Research Center,; Medical Lake 99022.

Abstract: Simian immunodeficiency virus (SIVMne) was isolated from 2 macaques after 4 and 6 weeks of treatment with the reverse transcriptase inhibitor PMEA. The first animal was pretreated with PMEA for 48 hours prior to SIV inoculation and was maintained on drug therapy for a total of 4 weeks. The second animal was chronically infected with SIV for 12 months and subsequently received PMEA for 6 weeks. Ficoll separated PBMCs from infected macaques and cell free virus stock were used to infect C-8166 cells in vitro at a multiplicity of infection of 1.0. To screen for PMEA resistance, drug was added to the cultures 24 hours post infection at concentrations of 0.2 microgram/ml to 200 micrograms/ml. The post-infection effective dose (ED50) has been found to be much higher than the preinfection ED50, necessitating the high concentrations of drug in our assays. Virus isolated from the drug pretreated animal was able to replicate in the presence of PMEA at a concentration of 100 micrograms/ml but not at 200 micrograms/ml. Virus isolated from the chronically infected animal was able to replicate at the maximum dose of 200 micrograms/ml. In comparison, virus from the stock used for inoculations could replicate in PMEA concentration of 20 micrograms/ml but not at 50 micrograms/ml. These results indicate that the virus isolates from PMEA treated macaques may be more resistant to the drug than virus from the original inoculum. Further studies will confirm the drug resistant phenotype and will focus on DNA sequencing of PMEA resistant isolates to identify corresponding base changes.

Keywords: Adenine/*ANALOGS & DERIVATIVES/TOXICITY/THERAPEUTIC USE Animal Antiviral Agents/*THERAPEUTIC USE Cell Line Comparative Study Dose-Response Relationship, Drug Drug Resistance, Microbial Lymphocytes/MICROBIOLOGY Macaca Simian Acquired Immunodeficiency Syndrome/*DRUG THERAPY SIV/*DRUG EFFECTS/ISOLATION & PURIF/PHYSIOLOGY Virus Replication/*DRUG EFFECTS ABSTRACT
940730
M9470923

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1994. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1994. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .