HIV quasispecies dynamics during pro-active treatment switching: impact on multi-drug resistance and resistance archiving in latent reservoirs.

摘要: The human immunodeficiency virus (HIV) can be suppressed by highly active anti-retroviral therapy (HAART) in the majority of infected patients. Nevertheless, treatment interruptions inevitably result viral rebounds from persistent, latently cells, necessitating lifelong treatment. Virological failure due to resistance development is a frequent event and major threat success. Currently, it recommended change after confirmation virological failure. However, at moment detected, drug resistant mutants already replicate great numbers. They infect numerous many which will turn into cells. This pool cells represents an archive resistance, has potential limiting future options. objective this study was design strategy for treatment-naive patients that decreases likelihood early preserves We propose apply single, pro-active switch, following period with induction regimen. main goal regimen decrease abundance randomly generated confer maintenance regimen, thereby increasing subsequent Treatment switched before overgrowth archiving mutant strains carry against would limit its re-use. In silico modelling shows optimal trade-off achieved switching days initiation antiviral therapy. Evaluation proposed demonstrated significant improvements terms response, as compared conventional HAART. While continuous alternation improved clinical outcome randomized trial, our results indicate similar improvement might also reached single switch. validity finding, however, remains shown corresponding trial.