No cross-resistance or selection of HIV-1 resistant mutants in vitro to the antiretroviral tripeptide glycyl-prolyl-glycine-amide.
The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of HIV-1 in vitro, probably by interfering with capsid formation. This study was aimed at determining cross-resistance between antiretroviral drugs and GPG-NH(2), and whether resistance to GPG-NH(2) can be induced in vitro. Fifty-five clinical HIV-1 isolates with different resistance-related mutations were tested for susceptibility to GPG-NH(2). No correlation between NRTI-, NNRTI- or PI-resistance and efficacy of GPG-NH(2) was found, indicating the lack of cross-resistance. Serial passages were performed with GPG-NH(2), and with lamivudine, and genotypic or phenotypic changes were determined. Resistance to lamivudine was detected after six passages. No resistance to GPG-NH(2) was generated after 30 passages in two parallel series. However, one mutation (T107I) in the p24 gene was detected in both series, but this mutation was not associated with decreased sensitivity to GPG-NH(2).
Andersson
Elin
E
Department of Clinical Virology, University of Göteborg, 413-46, Göteborg, Sweden. elin.andersson@microbio.gu.se
Horal
Peter
P
Vahlne
Anders
A
Svennerholm
Bo
B
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology*; D012641:Selection, Genetic
D019380:Anti-HIV Agents; D004279:DNA, Viral; D009842:Oligopeptides; C425285:glycylprolylglycine amide