AEGiS-05CROI: LiPa HIV-1 RT predicts phenotypic zidovudine resistance in HIV-1 patient isolates.

5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



LiPa HIV-1 RT predicts phenotypic zidovudine resistance in HIV-1 patient isolates.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:142 (abstract no. 333)

Schneider F, Plesseria JM, Stuyver L, Lambert C, Fontaine E, Kirpach P, Ninove D, Arendt V, Hemmer R, Schmit JC; Laboratoire de Retrovirologie, Luxembourg, Belgium.

We evaluated if ZDV-mutations detected by LiPA HIV-1 RT predict phenotypic resistance and correlate with surrogate maskers of HIV infection. LiPA HIV-1 RT, phenotypic ZDV resistance (ACTG protocol), viral load (Quantiplex, Chiron), ICD-p24 antigen, SI phenotype and CD4 counts were performed on 71 blood samples. 53 virus strains were sensitive to ZDV (IC(50) less than 0.16 micromolars), 10 were low-level resistant and 8 highly resistant (IC(50) greater than 1 micromolars). Mutants were found in 18 samples at codon 41, 20 at codon 70, and 26 at codon 215. For codon 41 and 215, but not 70, mutant stains had higher IC(50) values compared to wild-types or mixtures. In a same way, a correlation between mutations at codon 41 and 215, but not 70, and viral load, CD4 count, ICD p24 antigen and SI phenotype was found. Mutations at codons 41, 70 and 215 in the same sample, either as mixture or as pure mutant population, predicted ZDV-resistance with a positive predictive value of 80%. Only one sample contained all mutations as pure populations and correctly displayed high-level phenotypic resistance. The absence of ZDV-mutations resulted in a negative predictive value of 97% for LiPA HIV-1 RT. One of the reasons for discordance between LiPA HIV-1 RT and phenotypic resistance was the presence of a strain with the multidrug resistance mutation Q151M, which is not detected by the genotypic test. In conclusion, we found a significant correlation between the presence of ZDV-resistance mutations at codon 41 and 215 as detected by LiPA HIV-1 RT, phenotypic resistance and surrogate markers of HIV infection. Our results suggest that LiPA HIV-1 RT can be used as a rapid and reliable alternative to phenotypic resistance assays in clinical settings.

Keywords: AEGIS, Zidovudine, HIV-1, HIV Infections, HIV-1 Reverse Transcriptase, Anti-HIV Agents, Reverse Transcriptase Inhibitors, Viral Load, CD4 Lymphocyte Count, Codon, Mutation, Phenotype, Drug Resistance, Multiple, Human, genetics, AIDSKWDaegis,zidovudine,hiv-1,hivinfections,hiv-1reversetranscriptase,anti-hivagents,reversetranscriptaseinhibitors,viralload,cd4lymphocytecount,codon,mutation,phenotype,drugresistance,multiple,human,genetics,aids

1998-02-01
333

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.