Clonal analysis of HIV-1 variants in proviral DNA during treatment interruption in patients with multiple therapy failures

Abstract

Background Treatment interruption (TI) in antiretroviral-treated patients on virological failure (VF) often results in a shift from resistant to wild-type HIV-1 in plasma. A clonal analysis was set out to determine the importance of archiving of resistant HIV-1 variants during TI and its relationship with the occurrence of a VF after treatment resumption. Methods A fragment of the pol gene was cloned and sequenced from peripheral blood mononuclear cells DNA sampled at the end of TI. Clonal sequences were compared to bulk plasma sequences determined before TI, after TI and at VF. Results Four patients were enrolled; all had a complete reversion to wild-type HIV-1 at the end of TI. In two patients with subsequent VF, archiving of minority resistant variants was detected in proviral DNA. Archived resistant variants were found to be phylogenetically linked to sequences detected before TI and at VF, suggesting the re-expansion of resistant HIV-1 from archived quasispecies. Conclusion In patients having a TI in the context of VF, archiving of resistant HIV-1 variants in proviral DNA can be involved into the mechanisms of further VF after treatment resumption.