12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:19 (abstract no. 11185)

Ibanez A, Martinez MA, Puig T, Bonjoch A, Ruiz L
Fundacio Irsi-Caixa, Hospital Universitari Germans Trias I Pujol, Badalona, Spain.

BACKGROUND: To assess whether protease genomic fluctuations after indinavir therapy modify the env distribution of variants, we analysed the viral sequence evolution of the C2-V3 env and protease genes within four infected patients.

METHODS: Viral RNA from plasma samples obtained at the beginning of treatment and after 12 weeks of drug therapy were RT-PCR amplified. Product DNAs were cloned and 10 to 12 clones from each sample were sequenced.

RESULTS: Phylogenetic analysis from two patients who were transient responders showed that the env and protease sequences at the beginning of treatment clustered distinctly from sequences obtained after 12 weeks of therapy. Thus, quasispecies changes at the env locus were observed accompanying viral load rebounds and the emergence of indinavir resistant mutants. For these patients, the selective force produced by antiviral treatment with indinavir in the protease gene affected the evolution of other genomic regions, in particular the env gene. In contrast, the phylogenetic trees from two patients who were non responders to the therapy were found to have, for the two regions (env and protease), intermingled sequences from the two time points, suggesting that in the absence of viral population bottleneck env quasispecies changes were not detected.

CONCLUSION: These results document that population bottleneck during indinavir therapy causes a genetic drift not only in the protease gene but also in other genomic regions, in particular in the env quasispecies.

Copyright © 1998 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.