Mutations related to antiretroviral resistance identified by ultra-deep sequencing in two HIV-1 infected children submitted to structured interruptions of HAART.. Human immunodeficiency virus 1 strain:HIV-1

Structured Treatment Interruptions (STI) are considered as a possible alternative strategy to continuous antiretroviral therapy but their benefits and limitations have not yet been clearly established. Several studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, but low-abundance antiretroviral drug-resistant mutations (DRM) in viral populations at levels under limit of detection of conventional genotyping (<20% of quasispecies) could lead to virologic failure. In this work we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of DRM in the viral rebounds generated by the STI. There were no mutations associated with resistance to protease inhibitors but high-level and low-level DRM were detected for reverse transcriptase inhibitors. Thus, it cannot be concluded the safety of STI for patients and strict and carefully planned studies, with greater number of interrupt/restart cycles, are needed to evaluate the selection of DRM during STI.