One of the most interesting topics in the field of HIV/AIDS study is the possible relationship between HIV genetic penetrations and disease stages. One decade before, this kind of genomic information is difficult to achieve. Yet, the innovations of next generation sequencing (NGS) have changed this landscape. At present, new generations of bio-therapies target this undesired pathogenic pathways. In this article, we address the relationships between HIV-induced genomic changes across the history and different types of therapeutics have been testified since last decade—including integrate inhibitors, genome editing agents and therapeutic schedules. Future perspectives are also given.