Selection of zidovudine resistance mutations and escape of human immunodeficiency virus type 1 from antiretroviral pressure in stavudine-treated pediatric patients

The Journal of Infectious Diseases
Horst-Guenter MaxeinerMonique Nijhuis

Abstract

The relationship between clinical changes in stavudine activity and stavudine resistance was investigated in 16 human immunodeficiency virus (HIV)-infected children who received stavudine monotherapy for 18 months. Seven patients responded well to stavudine therapy, 3 experienced transient reductions in virus load, and all others had no detectable virologic response. In both the responders and nonresponders, no changes in stavudine susceptibility or specific baseline/emergent mutations in reverse transcriptase were observed. Only posttherapy HIV isolates from transient responders had elevated IC(50) values for stavudine. In 2 of the 3 transient responders, substitutions at codons 41, 210, and 215 were selected. The significance of these mutations was confirmed in viral competition experiments, site-directed mutagenesis, and in vitro selection. Selection of mutations previously associated with zidovudine resistance can be an important mechanism through which HIV may escape stavudine. The effect of these mutations on phenotypic stavudine susceptibility is relatively small but apparently large enough to be clinically significant.

Citations

Jan 19, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rangsima LolekhaJintanat Ananworanich
Feb 22, 2008·Virus Research·Javier Martinez-Picado, Miguel Angel Martínez
Nov 24, 2004·Anais Da Academia Brasileira De Ciências·Elizabeth S MachadoMarcelo A Soares
Nov 15, 2006·Journal of the International Association of Physicians in AIDS Care : JIAPAC·Ploenchan ChetchotisakdUNKNOWN Study Team
Apr 21, 2004·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Daniel R KuritzkesUNKNOWN Adult ACTG Protocol 306 370 Teams

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